Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Between March 7, 2018, and May 9, 2018, at least 164 people in Illinois were sickened by synthetic cannabinoids laced with rodenticides. The Illinois Department of Public Health has reported 4 deaths connected with the use of synthetic cannabinoids (sold under names such as Spice, K2, Legal Weed, etc).¹ Synthetic cannabinoids are mind-altering chemicals that are sprayed on dried plant material and often sold at convenience stores. Some users have reported smoking these substances because they are generally not detected by standard urine toxicology tests.

Recreational use of synthetic cannabinoids can lead to serious and, at times, deadly complications. Chemicals found in rat poison have contaminated batches of synthetic cannabinoids, leading to coagulopathy and severe bleeding. Affected patients have reported hemoptysis, hematuria, severe epistaxis, bleeding gums, conjunctival hemorrhages, and gastrointestinal bleeding. The following case is of a patient who presented to an emergency department (ED) with severe coagulopathy and cardiotoxicity after using an adulterated synthetic cannabinoid product.

Case Presentation

A 65-year-old man presented to the ED reporting hematochezia, hematuria, and hemoptysis. He reported that these symptoms began about 1 day after he had smoked a synthetic cannabinoid called K2. The patient stated that some of his friends who used the same product were experiencing similar symptoms. He reported mild generalized abdominal pain but reported no chest pain, dyspnea, headache, fevers, chills, or dysuria.

The patient’s past medical history included hypertension, dyslipidemia, chronic lower back pain, and vitamin D deficiency. His past surgical history was notable for an exploratory laparotomy after a stab wound to the abdomen. The patient reported taking the following medications: morphine SA 30 mg bid, meloxicam 15 mg daily, amitriptyline 100 mg qhs, amlodipine 5 mg daily, hydrocodone/acetaminophen 5/325 mg q12h prn, atorvastatin 20 mg qhs, omeprazole 20 mg qam, senna 187 mg daily prn, psyllium 1 packet dissolved in water daily prn, and cholecalciferol 1,000 IU daily.

The patient’s temperature was 98o F, blood pressure, 144/80 mm Hg; pulse, 131 beats per minute; respiratory rate, 18 breaths per minute; and O₂ saturation, 98% (ambient air). A physical examination revealed no acute distress; he was coughing up blood; clear lungs; heart sounds were tachycardic and irregularly irregular; soft, nondistended, mild generalized tenderness in the abdomen with no guarding and no rebound. The pertinent laboratory tests were international normalized ratio (INR), > 20; prothrombin time, > 150 seconds; prothrombin thromboplastin time, 157 seconds; hemoglobin, 13.3 g/dL; platelet count, 195 k/uL; white blood count, 11.3 k/uL; creatinine, 0.57mg/dL; potassium, 3.8 mmol/L, D-dimertest, 0.87 ug/mL fibrinogen equivalent units; fibrinogen level, 624 mg/dL; troponin, < 0.04 ng/mL; lactic acid, 1.3 mmol/L; total bilirubin, 0.8 mg/dL; alanine aminotransferase, 22 U/L, aspartate aminotransferase, 22 U/L; alkaline phosphatase, 89 U/L; urinalysis with > 50 red blood cells/high power field; large blood, negative leukocyte esterase, negative nitrite. The patient’s urine toxicology was negative for cannabinoids, methadone, amphetamines, cocaine, and benzodiazepines; but was positive for opiates. An anticoagulant poisoning panel also was ordered.

Treatment

In the ED, the case was discussed with the Illinois Poison Control Center. The patient was diagnosed with coagulopathy likely due to anticoagulant poisoning. He was immediately treated with 10 mg of IV vitamin K, a fixed dose of 2,000 units of 4-factor prothrombin complex concentrate, and 4 units of fresh frozen plasma. His INR improved to 1.42 within several hours. He received 5 mg of IV metoprolol for uncontrolled AF and was admitted to the intensive care unit (ICU) for further care.

In the ICU the patient was started on oral vitamin K 50 mg tid for ongoing treatment of coagulopathy due to concern for possible rodenticide poisoning associated with very long half-life. This dose was then decreased to 50 mg bid. He was given IV fluid resuscitation with normal saline and started on rate control for AF with oral metoprolol. His heart rate improved. An echocardiogram showed new cardiomyopathy with an ejection fraction of 25% to 30%. Given basilar infiltrates and 1 episode of low-grade fever, he was started on ceftriaxone for possible community-acquired pneumonia. The patient was started on cholestyramine to help with washout of the possible rodenticide. No endoscopic interventions were performed.

The patient was transferred to an inpatient telemetry floor 24 hours after admission to the ICU once his tachycardia and bleeding improved. He did not require transfusion of packed red blood cells. In the ICU his INR had ranged between 1.62 and 2.46 (down from > 20 in the ED). His hemoglobin dropped from 13.3 g/dL on admission to 12 g/dL on transfer from the ICU, before stabilizing around 11 g/dL on the floor. The patient’s heart rate required better control, so metoprolol was increased to a total daily dose of 200 mg on the telemetry floor. Oral digoxin was then added after a digoxin load for additional rate control, as the patient remained tachycardic. Twice a day the patient continued to take 50 mg vitamin K. Cholestyramine and ceftriaxone were initially continued, but when the INR started increasing again, the cholestyramine was stopped to allow for an increase to more frequent 3-times daily vitamin 50 mg K administration (cholestyramine can interfere with vitamin K absorption). According to the toxicology service, there was only weak evidence to support use of cholestyramine in this setting.

Given his ongoing mild hemoptysis, the patient received first 1 unit, and then another 4 units of FFP when the INR increased to 3.96 despite oral vitamin K. After FFP, the INR decreased to 1.93 and subsequently to 1.52. A CT of the chest showed patchy ground-glass densities throughout the lungs, predominantly at the lung bases and to a lesser extent in the upper lobes. The findings were felt to represent pulmonary hemorrhage given the patient’s history of hemoptysis (Figure 2). 

The patient’s heart rate control improved, and he remained hemodynamically stable. A thyroid function test was within normal limits. Lisinopril was added to metoprolol and digoxin given his newly diagnosed cardiomyopathy. The patient was observed for a total of 4 days on the inpatient floor and discharged after his INR stabilized around 1.5 on twice daily 50 mg vitamin K. The patient’s hematuria and hematochezia completely resolved, and hemoptysis was much improved at the time of discharge. His hemoglobin remained stable. The anticoagulant poisoning panel came back positive for difenacoum and brodifacoum. Given the long half-lives of these 2 substances, the patient required ongoing high-dose vitamin K therapy.
The patientwas seen 2 days and 9 days after hospital discharge by his primary care physician. He had no recurrence of bleeding. His INR had a slight upward trend from 1.50 to 1.70, so his vitamin K dose was increased to twice daily 60 mg vitamin K. A subsequent visit documented a follow-up INR of 1.28 on this higher dose. Six weeks after hospital discharge a repeat echocardiogram showed a recovered ejection fraction of 50% to 55%. A cardiology consult suggested that cardiomyopathy was largely tachycardia-induced and that with control of the ventricular rate, the cardiac function had recovered.

The patient has remained in AF at all follow-up visits. The INR normalized by 6 weeks after hospital discharge, and the dose of vitamin K slowly was tapered with close monitoring of the INR. Vitamin K was tapered for about 6 months after his initial presentation, and the patient was started on a direct oral anticoagulant (DOAC) for anticoagulation when the INR remained stable off vitamin K. He subsequently underwent a transesophageal echocardiogram followed by an attempt at direct current (DC) cardioversion; however, he did not remain in sinus rhythm, and is being continued on anticoagulation and rate control for his AF.

Discussion

Users generally smoke synthetic cannabinoids, which produce cannabis-like effects. However, atypical intoxication effects with worse complications often occur.² These products typically contain dried shredded plant material that is soaked in or sprayed with several synthetic cannabinoids, varying in dosage and combination.³ Synthetic cannabinoids have been associated with serious adverse effects (AEs), including drowsiness, light-headedness, and fast or irregular heartbeat.⁴ More severe clinical features such as psychosis, delirium, cardiotoxicity, seizures, rhabdomyolysis, acute kidney injury, hyperthermia, myocardial ischemia, ischemic strokes, and death have also been noted.⁴

It is not known how some batches of synthetic cannabinoids came to be contaminated with rat poison or how commonly such an adulteration is found across the country. Several different guidelines provide pathways for the treatment of acute bleeding in the setting of coagulopathy due to vitamin K antagonists.^5,6 Each guideline divides the indications for reversal into either severity of bleeding or the criticality of the bleeding based on location.^5,6 All guidelines recommend the use of vitamin K (either oral or IV) followed by FFP or 4-factor prothrombin complex concentrate (PCC) for more severe bleeding.^5,6 However, recommendations regarding the use of PCC vary in dosing for vitamin K antagonists (in contrast to treatment of coagulopathy due to DOACs). Recent studies and guidelines suggest that fixed-dose (rather than weight-based dose) PCC is effective for the reversal of coagulopathy due to vitamin K antagonists.^6,7 Using fixed rather than weight-based dosing decreases cost and may decrease the possibility of thrombotic AEs.⁷ In this patient, a fixed-dose of 2,000 units of PCC was given based on data that were extrapolated from warfarin reversal using PCC.⁷

The vitamin K antagonists that adulterated this patient’s synthetic cannabinoid were difenacoum and brodifacoum, which are 4-hydroxycoumarin derivatives. These are second-generation long-acting anticoagulant rodenticides (LAARs) that are about 100 times more potent than warfarin.⁸ As the name implies, LAARs have a longer duration of action in the body of any organism that ingests the poison, which is due to the highly lipophilic groups that have been added to the warfarin molecule to combat resistance in rodents.⁹

As a result of the deposition in the tissues, there have been reports of the duration of action of brodifacoum ranging from 51 days to 9 months after ingestion, with the latter caused by an intentional overdose in a human.^9-12 Reports suggest that coagulopathy is not likely to occur when the serum brodifacoum concentration is < 10 ng/mL.^13,14 Animal models show difenacoum has a tissue half-life of about 62 days.¹⁵ Reports of difenacoum poisoning in humans have shown variable lengths of treatment, ranging from 30 to 47 days.^16-18 The length of treatment for either brodifacoum or difenacoum will depend on the amount of poison exposure.

The long duration of action and treatment duration may lead to problems with drug procurement, especially in the early phase of treatment in which IV vitamin K is used. The supply of IV vitamin K recently has been limited for at least some manufacturers. According to the American Society of Health System Pharmacists Current Drug Shortage List, the increased demand is thought to be due to increased use of synthetic inhaled cannabinoids laced with anticoagulant.¹⁹ IV vitamin K products are available from suppliers such as Amphastar (Rancho Cucamonga, CA) and Hospira (Lake Forest, IL).

The American College of Chest Physicians recommends IV vitamin K administration in patients with major bleeding secondary to vitamin K antagonists.²⁰ The oral route is thought to be more effective than a subcutaneous route in the treatment of nonbleeding patients with rodenticide-associated coagulopathy. Due to erratic and unpredictable absorption, the subcutaneous route of administration has fallen out of favor. Oral vitamin K products were not affected by the recent shortage. However, large doses of oral vitamin K can be costly. Due to the long half-life of LAAR, many patients are discharged with a prescription for oral vitamin K. Although vitamin K is found in most over-the-counter (OTC) multivitamins, the strength is insufficient. Most OTC formulations are ≤ 100 μg, whereas the prescription strength is 5 mg, but patients being treated for rodenticide poisoning require much larger doses.

Commercial insurance carriers and Medicare Part D usually do not cover vitamins and minerals unless it is for a medically accepted indication or is an indication supported by citation in either the American Hospital Formulary System, United States Pharmacopeia drug information book, or an electronic information resource that is supported by evidence such as Micromedex.²¹ For a patient without insurance coverage being treated with high-dose vitamin K therapy for rodenticide poisoning outside of a federal health care system, the cost could be as high as $500 to $1,000 per day, depending on the dose of vitamin K needed to maintain an acceptable INR.

Conclusion

In addition to bleeding as a result of coagulopathy, this patient presented with new onset of AF with rapid ventricular response and a newly diagnosed cardiomyopathy. Although the patient had other cardiovascular risk factors, such as hypertension, dyslipidemia, and a remote history of cocaine use, it is likely that the use of the synthetic cannabinoids contributed to the development and/or worsening of this arrhythmia and cardiomyopathy. The patient remained in AF 6 weeks after hospital discharge with a controlled ventricular rate on metoprolol and digoxin. An interval echocardiogram 6 weeks after hospital discharge showed a recovered ejection fraction. In cases of tachycardia-induced cardiomyopathy, the ejection fraction often recovers with control of the tachycardia. The patient was weaned off vitamin K about 6 months after his initial presentation and started on a DOAC for anticoagulation. He subsequently underwent a transesophageal echocardiogram followed by an attempt at DC cardioversion; however, he did not remain in sinus rhythm and is being continued on anticoagulation and rate control for his AF.

Although unclear how synthetic cannabinoids became adulterated with a potent vitamin K antagonist, health care practitioners should consider this if a patient presents with unexplained coagulopathy and widespread bleeding. Fixed-dose PCC should be considered as an alternative to weight-based dosing in these cases. Physicians and pharmacy personnel should anticipate a need for long-term high doses of vitamin K in order to begin work early to obtain sufficient supplies to treat presenting patients.

Between March 7, 2018, and May 9, 2018, at least 164 people in Illinois were sickened by synthetic cannabinoids laced with rodenticides. The Illinois Department of Public Health has reported 4 deaths connected with the use of synthetic cannabinoids (sold under names such as Spice, K2, Legal Weed, etc).¹ Synthetic cannabinoids are mind-altering chemicals that are sprayed on dried plant material and often sold at convenience stores. Some users have reported smoking these substances because they are generally not detected by standard urine toxicology tests.

Recreational use of synthetic cannabinoids can lead to serious and, at times, deadly complications. Chemicals found in rat poison have contaminated batches of synthetic cannabinoids, leading to coagulopathy and severe bleeding. Affected patients have reported hemoptysis, hematuria, severe epistaxis, bleeding gums, conjunctival hemorrhages, and gastrointestinal bleeding. The following case is of a patient who presented to an emergency department (ED) with severe coagulopathy and cardiotoxicity after using an adulterated synthetic cannabinoid product.

Case Presentation

A 65-year-old man presented to the ED reporting hematochezia, hematuria, and hemoptysis. He reported that these symptoms began about 1 day after he had smoked a synthetic cannabinoid called K2. The patient stated that some of his friends who used the same product were experiencing similar symptoms. He reported mild generalized abdominal pain but reported no chest pain, dyspnea, headache, fevers, chills, or dysuria.

The patient’s past medical history included hypertension, dyslipidemia, chronic lower back pain, and vitamin D deficiency. His past surgical history was notable for an exploratory laparotomy after a stab wound to the abdomen. The patient reported taking the following medications: morphine SA 30 mg bid, meloxicam 15 mg daily, amitriptyline 100 mg qhs, amlodipine 5 mg daily, hydrocodone/acetaminophen 5/325 mg q12h prn, atorvastatin 20 mg qhs, omeprazole 20 mg qam, senna 187 mg daily prn, psyllium 1 packet dissolved in water daily prn, and cholecalciferol 1,000 IU daily.

The patient’s temperature was 98o F, blood pressure, 144/80 mm Hg; pulse, 131 beats per minute; respiratory rate, 18 breaths per minute; and O₂ saturation, 98% (ambient air). A physical examination revealed no acute distress; he was coughing up blood; clear lungs; heart sounds were tachycardic and irregularly irregular; soft, nondistended, mild generalized tenderness in the abdomen with no guarding and no rebound. The pertinent laboratory tests were international normalized ratio (INR), > 20; prothrombin time, > 150 seconds; prothrombin thromboplastin time, 157 seconds; hemoglobin, 13.3 g/dL; platelet count, 195 k/uL; white blood count, 11.3 k/uL; creatinine, 0.57mg/dL; potassium, 3.8 mmol/L, D-dimertest, 0.87 ug/mL fibrinogen equivalent units; fibrinogen level, 624 mg/dL; troponin, < 0.04 ng/mL; lactic acid, 1.3 mmol/L; total bilirubin, 0.8 mg/dL; alanine aminotransferase, 22 U/L, aspartate aminotransferase, 22 U/L; alkaline phosphatase, 89 U/L; urinalysis with > 50 red blood cells/high power field; large blood, negative leukocyte esterase, negative nitrite. The patient’s urine toxicology was negative for cannabinoids, methadone, amphetamines, cocaine, and benzodiazepines; but was positive for opiates. An anticoagulant poisoning panel also was ordered.

Treatment

In the ED, the case was discussed with the Illinois Poison Control Center. The patient was diagnosed with coagulopathy likely due to anticoagulant poisoning. He was immediately treated with 10 mg of IV vitamin K, a fixed dose of 2,000 units of 4-factor prothrombin complex concentrate, and 4 units of fresh frozen plasma. His INR improved to 1.42 within several hours. He received 5 mg of IV metoprolol for uncontrolled AF and was admitted to the intensive care unit (ICU) for further care.

In the ICU the patient was started on oral vitamin K 50 mg tid for ongoing treatment of coagulopathy due to concern for possible rodenticide poisoning associated with very long half-life. This dose was then decreased to 50 mg bid. He was given IV fluid resuscitation with normal saline and started on rate control for AF with oral metoprolol. His heart rate improved. An echocardiogram showed new cardiomyopathy with an ejection fraction of 25% to 30%. Given basilar infiltrates and 1 episode of low-grade fever, he was started on ceftriaxone for possible community-acquired pneumonia. The patient was started on cholestyramine to help with washout of the possible rodenticide. No endoscopic interventions were performed.

The patient was transferred to an inpatient telemetry floor 24 hours after admission to the ICU once his tachycardia and bleeding improved. He did not require transfusion of packed red blood cells. In the ICU his INR had ranged between 1.62 and 2.46 (down from > 20 in the ED). His hemoglobin dropped from 13.3 g/dL on admission to 12 g/dL on transfer from the ICU, before stabilizing around 11 g/dL on the floor. The patient’s heart rate required better control, so metoprolol was increased to a total daily dose of 200 mg on the telemetry floor. Oral digoxin was then added after a digoxin load for additional rate control, as the patient remained tachycardic. Twice a day the patient continued to take 50 mg vitamin K. Cholestyramine and ceftriaxone were initially continued, but when the INR started increasing again, the cholestyramine was stopped to allow for an increase to more frequent 3-times daily vitamin 50 mg K administration (cholestyramine can interfere with vitamin K absorption). According to the toxicology service, there was only weak evidence to support use of cholestyramine in this setting.

Given his ongoing mild hemoptysis, the patient received first 1 unit, and then another 4 units of FFP when the INR increased to 3.96 despite oral vitamin K. After FFP, the INR decreased to 1.93 and subsequently to 1.52. A CT of the chest showed patchy ground-glass densities throughout the lungs, predominantly at the lung bases and to a lesser extent in the upper lobes. The findings were felt to represent pulmonary hemorrhage given the patient’s history of hemoptysis (Figure 2). 

The patient’s heart rate control improved, and he remained hemodynamically stable. A thyroid function test was within normal limits. Lisinopril was added to metoprolol and digoxin given his newly diagnosed cardiomyopathy. The patient was observed for a total of 4 days on the inpatient floor and discharged after his INR stabilized around 1.5 on twice daily 50 mg vitamin K. The patient’s hematuria and hematochezia completely resolved, and hemoptysis was much improved at the time of discharge. His hemoglobin remained stable. The anticoagulant poisoning panel came back positive for difenacoum and brodifacoum. Given the long half-lives of these 2 substances, the patient required ongoing high-dose vitamin K therapy.
The patientwas seen 2 days and 9 days after hospital discharge by his primary care physician. He had no recurrence of bleeding. His INR had a slight upward trend from 1.50 to 1.70, so his vitamin K dose was increased to twice daily 60 mg vitamin K. A subsequent visit documented a follow-up INR of 1.28 on this higher dose. Six weeks after hospital discharge a repeat echocardiogram showed a recovered ejection fraction of 50% to 55%. A cardiology consult suggested that cardiomyopathy was largely tachycardia-induced and that with control of the ventricular rate, the cardiac function had recovered.

The patient has remained in AF at all follow-up visits. The INR normalized by 6 weeks after hospital discharge, and the dose of vitamin K slowly was tapered with close monitoring of the INR. Vitamin K was tapered for about 6 months after his initial presentation, and the patient was started on a direct oral anticoagulant (DOAC) for anticoagulation when the INR remained stable off vitamin K. He subsequently underwent a transesophageal echocardiogram followed by an attempt at direct current (DC) cardioversion; however, he did not remain in sinus rhythm, and is being continued on anticoagulation and rate control for his AF.

Discussion

Users generally smoke synthetic cannabinoids, which produce cannabis-like effects. However, atypical intoxication effects with worse complications often occur.² These products typically contain dried shredded plant material that is soaked in or sprayed with several synthetic cannabinoids, varying in dosage and combination.³ Synthetic cannabinoids have been associated with serious adverse effects (AEs), including drowsiness, light-headedness, and fast or irregular heartbeat.⁴ More severe clinical features such as psychosis, delirium, cardiotoxicity, seizures, rhabdomyolysis, acute kidney injury, hyperthermia, myocardial ischemia, ischemic strokes, and death have also been noted.⁴

It is not known how some batches of synthetic cannabinoids came to be contaminated with rat poison or how commonly such an adulteration is found across the country. Several different guidelines provide pathways for the treatment of acute bleeding in the setting of coagulopathy due to vitamin K antagonists.^5,6 Each guideline divides the indications for reversal into either severity of bleeding or the criticality of the bleeding based on location.^5,6 All guidelines recommend the use of vitamin K (either oral or IV) followed by FFP or 4-factor prothrombin complex concentrate (PCC) for more severe bleeding.^5,6 However, recommendations regarding the use of PCC vary in dosing for vitamin K antagonists (in contrast to treatment of coagulopathy due to DOACs). Recent studies and guidelines suggest that fixed-dose (rather than weight-based dose) PCC is effective for the reversal of coagulopathy due to vitamin K antagonists.^6,7 Using fixed rather than weight-based dosing decreases cost and may decrease the possibility of thrombotic AEs.⁷ In this patient, a fixed-dose of 2,000 units of PCC was given based on data that were extrapolated from warfarin reversal using PCC.⁷

The vitamin K antagonists that adulterated this patient’s synthetic cannabinoid were difenacoum and brodifacoum, which are 4-hydroxycoumarin derivatives. These are second-generation long-acting anticoagulant rodenticides (LAARs) that are about 100 times more potent than warfarin.⁸ As the name implies, LAARs have a longer duration of action in the body of any organism that ingests the poison, which is due to the highly lipophilic groups that have been added to the warfarin molecule to combat resistance in rodents.⁹

As a result of the deposition in the tissues, there have been reports of the duration of action of brodifacoum ranging from 51 days to 9 months after ingestion, with the latter caused by an intentional overdose in a human.^9-12 Reports suggest that coagulopathy is not likely to occur when the serum brodifacoum concentration is < 10 ng/mL.^13,14 Animal models show difenacoum has a tissue half-life of about 62 days.¹⁵ Reports of difenacoum poisoning in humans have shown variable lengths of treatment, ranging from 30 to 47 days.^16-18 The length of treatment for either brodifacoum or difenacoum will depend on the amount of poison exposure.

The long duration of action and treatment duration may lead to problems with drug procurement, especially in the early phase of treatment in which IV vitamin K is used. The supply of IV vitamin K recently has been limited for at least some manufacturers. According to the American Society of Health System Pharmacists Current Drug Shortage List, the increased demand is thought to be due to increased use of synthetic inhaled cannabinoids laced with anticoagulant.¹⁹ IV vitamin K products are available from suppliers such as Amphastar (Rancho Cucamonga, CA) and Hospira (Lake Forest, IL).

The American College of Chest Physicians recommends IV vitamin K administration in patients with major bleeding secondary to vitamin K antagonists.²⁰ The oral route is thought to be more effective than a subcutaneous route in the treatment of nonbleeding patients with rodenticide-associated coagulopathy. Due to erratic and unpredictable absorption, the subcutaneous route of administration has fallen out of favor. Oral vitamin K products were not affected by the recent shortage. However, large doses of oral vitamin K can be costly. Due to the long half-life of LAAR, many patients are discharged with a prescription for oral vitamin K. Although vitamin K is found in most over-the-counter (OTC) multivitamins, the strength is insufficient. Most OTC formulations are ≤ 100 μg, whereas the prescription strength is 5 mg, but patients being treated for rodenticide poisoning require much larger doses.

Commercial insurance carriers and Medicare Part D usually do not cover vitamins and minerals unless it is for a medically accepted indication or is an indication supported by citation in either the American Hospital Formulary System, United States Pharmacopeia drug information book, or an electronic information resource that is supported by evidence such as Micromedex.²¹ For a patient without insurance coverage being treated with high-dose vitamin K therapy for rodenticide poisoning outside of a federal health care system, the cost could be as high as $500 to $1,000 per day, depending on the dose of vitamin K needed to maintain an acceptable INR.

Conclusion

In addition to bleeding as a result of coagulopathy, this patient presented with new onset of AF with rapid ventricular response and a newly diagnosed cardiomyopathy. Although the patient had other cardiovascular risk factors, such as hypertension, dyslipidemia, and a remote history of cocaine use, it is likely that the use of the synthetic cannabinoids contributed to the development and/or worsening of this arrhythmia and cardiomyopathy. The patient remained in AF 6 weeks after hospital discharge with a controlled ventricular rate on metoprolol and digoxin. An interval echocardiogram 6 weeks after hospital discharge showed a recovered ejection fraction. In cases of tachycardia-induced cardiomyopathy, the ejection fraction often recovers with control of the tachycardia. The patient was weaned off vitamin K about 6 months after his initial presentation and started on a DOAC for anticoagulation. He subsequently underwent a transesophageal echocardiogram followed by an attempt at DC cardioversion; however, he did not remain in sinus rhythm and is being continued on anticoagulation and rate control for his AF.

Although unclear how synthetic cannabinoids became adulterated with a potent vitamin K antagonist, health care practitioners should consider this if a patient presents with unexplained coagulopathy and widespread bleeding. Fixed-dose PCC should be considered as an alternative to weight-based dosing in these cases. Physicians and pharmacy personnel should anticipate a need for long-term high doses of vitamin K in order to begin work early to obtain sufficient supplies to treat presenting patients.

Between March 7, 2018, and May 9, 2018, at least 164 people in Illinois were sickened by synthetic cannabinoids laced with rodenticides. The Illinois Department of Public Health has reported 4 deaths connected with the use of synthetic cannabinoids (sold under names such as Spice, K2, Legal Weed, etc).¹ Synthetic cannabinoids are mind-altering chemicals that are sprayed on dried plant material and often sold at convenience stores. Some users have reported smoking these substances because they are generally not detected by standard urine toxicology tests.

Recreational use of synthetic cannabinoids can lead to serious and, at times, deadly complications. Chemicals found in rat poison have contaminated batches of synthetic cannabinoids, leading to coagulopathy and severe bleeding. Affected patients have reported hemoptysis, hematuria, severe epistaxis, bleeding gums, conjunctival hemorrhages, and gastrointestinal bleeding. The following case is of a patient who presented to an emergency department (ED) with severe coagulopathy and cardiotoxicity after using an adulterated synthetic cannabinoid product.

Case Presentation

A 65-year-old man presented to the ED reporting hematochezia, hematuria, and hemoptysis. He reported that these symptoms began about 1 day after he had smoked a synthetic cannabinoid called K2. The patient stated that some of his friends who used the same product were experiencing similar symptoms. He reported mild generalized abdominal pain but reported no chest pain, dyspnea, headache, fevers, chills, or dysuria.

The patient’s past medical history included hypertension, dyslipidemia, chronic lower back pain, and vitamin D deficiency. His past surgical history was notable for an exploratory laparotomy after a stab wound to the abdomen. The patient reported taking the following medications: morphine SA 30 mg bid, meloxicam 15 mg daily, amitriptyline 100 mg qhs, amlodipine 5 mg daily, hydrocodone/acetaminophen 5/325 mg q12h prn, atorvastatin 20 mg qhs, omeprazole 20 mg qam, senna 187 mg daily prn, psyllium 1 packet dissolved in water daily prn, and cholecalciferol 1,000 IU daily.

The patient’s temperature was 98o F, blood pressure, 144/80 mm Hg; pulse, 131 beats per minute; respiratory rate, 18 breaths per minute; and O₂ saturation, 98% (ambient air). A physical examination revealed no acute distress; he was coughing up blood; clear lungs; heart sounds were tachycardic and irregularly irregular; soft, nondistended, mild generalized tenderness in the abdomen with no guarding and no rebound. The pertinent laboratory tests were international normalized ratio (INR), > 20; prothrombin time, > 150 seconds; prothrombin thromboplastin time, 157 seconds; hemoglobin, 13.3 g/dL; platelet count, 195 k/uL; white blood count, 11.3 k/uL; creatinine, 0.57mg/dL; potassium, 3.8 mmol/L, D-dimertest, 0.87 ug/mL fibrinogen equivalent units; fibrinogen level, 624 mg/dL; troponin, < 0.04 ng/mL; lactic acid, 1.3 mmol/L; total bilirubin, 0.8 mg/dL; alanine aminotransferase, 22 U/L, aspartate aminotransferase, 22 U/L; alkaline phosphatase, 89 U/L; urinalysis with > 50 red blood cells/high power field; large blood, negative leukocyte esterase, negative nitrite. The patient’s urine toxicology was negative for cannabinoids, methadone, amphetamines, cocaine, and benzodiazepines; but was positive for opiates. An anticoagulant poisoning panel also was ordered.

Treatment

In the ED, the case was discussed with the Illinois Poison Control Center. The patient was diagnosed with coagulopathy likely due to anticoagulant poisoning. He was immediately treated with 10 mg of IV vitamin K, a fixed dose of 2,000 units of 4-factor prothrombin complex concentrate, and 4 units of fresh frozen plasma. His INR improved to 1.42 within several hours. He received 5 mg of IV metoprolol for uncontrolled AF and was admitted to the intensive care unit (ICU) for further care.

In the ICU the patient was started on oral vitamin K 50 mg tid for ongoing treatment of coagulopathy due to concern for possible rodenticide poisoning associated with very long half-life. This dose was then decreased to 50 mg bid. He was given IV fluid resuscitation with normal saline and started on rate control for AF with oral metoprolol. His heart rate improved. An echocardiogram showed new cardiomyopathy with an ejection fraction of 25% to 30%. Given basilar infiltrates and 1 episode of low-grade fever, he was started on ceftriaxone for possible community-acquired pneumonia. The patient was started on cholestyramine to help with washout of the possible rodenticide. No endoscopic interventions were performed.

The patient was transferred to an inpatient telemetry floor 24 hours after admission to the ICU once his tachycardia and bleeding improved. He did not require transfusion of packed red blood cells. In the ICU his INR had ranged between 1.62 and 2.46 (down from > 20 in the ED). His hemoglobin dropped from 13.3 g/dL on admission to 12 g/dL on transfer from the ICU, before stabilizing around 11 g/dL on the floor. The patient’s heart rate required better control, so metoprolol was increased to a total daily dose of 200 mg on the telemetry floor. Oral digoxin was then added after a digoxin load for additional rate control, as the patient remained tachycardic. Twice a day the patient continued to take 50 mg vitamin K. Cholestyramine and ceftriaxone were initially continued, but when the INR started increasing again, the cholestyramine was stopped to allow for an increase to more frequent 3-times daily vitamin 50 mg K administration (cholestyramine can interfere with vitamin K absorption). According to the toxicology service, there was only weak evidence to support use of cholestyramine in this setting.

Given his ongoing mild hemoptysis, the patient received first 1 unit, and then another 4 units of FFP when the INR increased to 3.96 despite oral vitamin K. After FFP, the INR decreased to 1.93 and subsequently to 1.52. A CT of the chest showed patchy ground-glass densities throughout the lungs, predominantly at the lung bases and to a lesser extent in the upper lobes. The findings were felt to represent pulmonary hemorrhage given the patient’s history of hemoptysis (Figure 2). 

The patient’s heart rate control improved, and he remained hemodynamically stable. A thyroid function test was within normal limits. Lisinopril was added to metoprolol and digoxin given his newly diagnosed cardiomyopathy. The patient was observed for a total of 4 days on the inpatient floor and discharged after his INR stabilized around 1.5 on twice daily 50 mg vitamin K. The patient’s hematuria and hematochezia completely resolved, and hemoptysis was much improved at the time of discharge. His hemoglobin remained stable. The anticoagulant poisoning panel came back positive for difenacoum and brodifacoum. Given the long half-lives of these 2 substances, the patient required ongoing high-dose vitamin K therapy.
The patientwas seen 2 days and 9 days after hospital discharge by his primary care physician. He had no recurrence of bleeding. His INR had a slight upward trend from 1.50 to 1.70, so his vitamin K dose was increased to twice daily 60 mg vitamin K. A subsequent visit documented a follow-up INR of 1.28 on this higher dose. Six weeks after hospital discharge a repeat echocardiogram showed a recovered ejection fraction of 50% to 55%. A cardiology consult suggested that cardiomyopathy was largely tachycardia-induced and that with control of the ventricular rate, the cardiac function had recovered.

The patient has remained in AF at all follow-up visits. The INR normalized by 6 weeks after hospital discharge, and the dose of vitamin K slowly was tapered with close monitoring of the INR. Vitamin K was tapered for about 6 months after his initial presentation, and the patient was started on a direct oral anticoagulant (DOAC) for anticoagulation when the INR remained stable off vitamin K. He subsequently underwent a transesophageal echocardiogram followed by an attempt at direct current (DC) cardioversion; however, he did not remain in sinus rhythm, and is being continued on anticoagulation and rate control for his AF.

Discussion

Users generally smoke synthetic cannabinoids, which produce cannabis-like effects. However, atypical intoxication effects with worse complications often occur.² These products typically contain dried shredded plant material that is soaked in or sprayed with several synthetic cannabinoids, varying in dosage and combination.³ Synthetic cannabinoids have been associated with serious adverse effects (AEs), including drowsiness, light-headedness, and fast or irregular heartbeat.⁴ More severe clinical features such as psychosis, delirium, cardiotoxicity, seizures, rhabdomyolysis, acute kidney injury, hyperthermia, myocardial ischemia, ischemic strokes, and death have also been noted.⁴

It is not known how some batches of synthetic cannabinoids came to be contaminated with rat poison or how commonly such an adulteration is found across the country. Several different guidelines provide pathways for the treatment of acute bleeding in the setting of coagulopathy due to vitamin K antagonists.^5,6 Each guideline divides the indications for reversal into either severity of bleeding or the criticality of the bleeding based on location.^5,6 All guidelines recommend the use of vitamin K (either oral or IV) followed by FFP or 4-factor prothrombin complex concentrate (PCC) for more severe bleeding.^5,6 However, recommendations regarding the use of PCC vary in dosing for vitamin K antagonists (in contrast to treatment of coagulopathy due to DOACs). Recent studies and guidelines suggest that fixed-dose (rather than weight-based dose) PCC is effective for the reversal of coagulopathy due to vitamin K antagonists.^6,7 Using fixed rather than weight-based dosing decreases cost and may decrease the possibility of thrombotic AEs.⁷ In this patient, a fixed-dose of 2,000 units of PCC was given based on data that were extrapolated from warfarin reversal using PCC.⁷

The vitamin K antagonists that adulterated this patient’s synthetic cannabinoid were difenacoum and brodifacoum, which are 4-hydroxycoumarin derivatives. These are second-generation long-acting anticoagulant rodenticides (LAARs) that are about 100 times more potent than warfarin.⁸ As the name implies, LAARs have a longer duration of action in the body of any organism that ingests the poison, which is due to the highly lipophilic groups that have been added to the warfarin molecule to combat resistance in rodents.⁹

As a result of the deposition in the tissues, there have been reports of the duration of action of brodifacoum ranging from 51 days to 9 months after ingestion, with the latter caused by an intentional overdose in a human.^9-12 Reports suggest that coagulopathy is not likely to occur when the serum brodifacoum concentration is < 10 ng/mL.^13,14 Animal models show difenacoum has a tissue half-life of about 62 days.¹⁵ Reports of difenacoum poisoning in humans have shown variable lengths of treatment, ranging from 30 to 47 days.^16-18 The length of treatment for either brodifacoum or difenacoum will depend on the amount of poison exposure.

The long duration of action and treatment duration may lead to problems with drug procurement, especially in the early phase of treatment in which IV vitamin K is used. The supply of IV vitamin K recently has been limited for at least some manufacturers. According to the American Society of Health System Pharmacists Current Drug Shortage List, the increased demand is thought to be due to increased use of synthetic inhaled cannabinoids laced with anticoagulant.¹⁹ IV vitamin K products are available from suppliers such as Amphastar (Rancho Cucamonga, CA) and Hospira (Lake Forest, IL).

The American College of Chest Physicians recommends IV vitamin K administration in patients with major bleeding secondary to vitamin K antagonists.²⁰ The oral route is thought to be more effective than a subcutaneous route in the treatment of nonbleeding patients with rodenticide-associated coagulopathy. Due to erratic and unpredictable absorption, the subcutaneous route of administration has fallen out of favor. Oral vitamin K products were not affected by the recent shortage. However, large doses of oral vitamin K can be costly. Due to the long half-life of LAAR, many patients are discharged with a prescription for oral vitamin K. Although vitamin K is found in most over-the-counter (OTC) multivitamins, the strength is insufficient. Most OTC formulations are ≤ 100 μg, whereas the prescription strength is 5 mg, but patients being treated for rodenticide poisoning require much larger doses.

Commercial insurance carriers and Medicare Part D usually do not cover vitamins and minerals unless it is for a medically accepted indication or is an indication supported by citation in either the American Hospital Formulary System, United States Pharmacopeia drug information book, or an electronic information resource that is supported by evidence such as Micromedex.²¹ For a patient without insurance coverage being treated with high-dose vitamin K therapy for rodenticide poisoning outside of a federal health care system, the cost could be as high as $500 to $1,000 per day, depending on the dose of vitamin K needed to maintain an acceptable INR.

Conclusion

In addition to bleeding as a result of coagulopathy, this patient presented with new onset of AF with rapid ventricular response and a newly diagnosed cardiomyopathy. Although the patient had other cardiovascular risk factors, such as hypertension, dyslipidemia, and a remote history of cocaine use, it is likely that the use of the synthetic cannabinoids contributed to the development and/or worsening of this arrhythmia and cardiomyopathy. The patient remained in AF 6 weeks after hospital discharge with a controlled ventricular rate on metoprolol and digoxin. An interval echocardiogram 6 weeks after hospital discharge showed a recovered ejection fraction. In cases of tachycardia-induced cardiomyopathy, the ejection fraction often recovers with control of the tachycardia. The patient was weaned off vitamin K about 6 months after his initial presentation and started on a DOAC for anticoagulation. He subsequently underwent a transesophageal echocardiogram followed by an attempt at DC cardioversion; however, he did not remain in sinus rhythm and is being continued on anticoagulation and rate control for his AF.

Although unclear how synthetic cannabinoids became adulterated with a potent vitamin K antagonist, health care practitioners should consider this if a patient presents with unexplained coagulopathy and widespread bleeding. Fixed-dose PCC should be considered as an alternative to weight-based dosing in these cases. Physicians and pharmacy personnel should anticipate a need for long-term high doses of vitamin K in order to begin work early to obtain sufficient supplies to treat presenting patients.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.

BIRMINGHAM, ENGLAND – Higher blood biologic drug levels in the first year of treatment for rheumatoid arthritis independently increased the risk of any infection by about 50% when compared against low or normal levels in a new observational cohort study, providing support for monitoring biologic drug levels to help to predict infection risk.

Data from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA) that were presented at the British Society for Rheumatology annual conference showed that the adjusted hazard ratio for any infection occurring within the first year among patients with high drug levels was 1.51, with a 95% confidence interval (CI) of 1.14 to 2.01. The adjustments took into account patients’ age, gender, disease activity score, and use of methotrexate.

There are more than 10 biologics now available for use in rheumatoid arthritis but deciding which to use in a particular patient remains very much “a trial and error approach,” first author Meghna Jani, MBChB, said at the conference.

Sara Freeman/MDedge News

“From a patient perspective, one of the most important concerns continues to be the risk of serious infections and adverse events,” added Dr. Jani, a National Institute for Health Research Academic Clinical Lecturer in Rheumatology at the University of Manchester (England).

The link between biologic agents and infections, including those that could result in hospitalization or other serious consequences, has been well studied in biologics registries. It is known, for example, that the risk of infections with tumor necrosis factor inhibitor treatment seems to be highest during the first 6-12 months of treatment.

According to Dr. Jani, conventional means of determining risk – such as patient age and the presence of comorbid factors – have limited benefit in terms of deciding which patients could be at heightened risk of infections. “Ideally, we need biomarkers in rheumatology that can be implemented in clinical practice and help us predict efficacy and safety, as well as help us use these medications much more cost-effectively,” she said.

Four years ago, a meta-analysis (Lancet. 2015;386:258-65) suggested that the risk of infection may be linked to using higher doses of anti–tumor necrosis factor drugs, which led the BSRBR-RA team to see if elevated levels of these drugs in the serum could be predictive of the infection risk and thus used as a possible biomarker. There was also prior evidence that serum drug concentrations of biologics were associated with long-term treatment response and that a certain level was needed to determine the likely treatment response.

In the current study, Dr. Jani and colleagues used data on 703 patients with rheumatoid arthritis starting biologic therapy who were simultaneously recruited into the BSRBR-RA, which has been running since 2001, and the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS). The BSRBR-RA did not collect biological samples, but in BRAGGSS serological samples were collected at 3-, 6-, and 12-month intervals after the start of a biologic treatment, along with other assessments. This is the first time two national, U.K.-based, rheumatoid arthritis cohorts have been linked in this way, Dr. Jani said.

Serum samples taken from the patients were assessed via enzyme-linked immunoassay to determine levels of the biologic agent used, with high drug levels defined as more than 4 mcg/mL for etanercept (n = 286), tocilizumab (n = 104), and infliximab (n = 14); more than 8 mcg/mL for adalimumab (n = 179), and 25 mcg/mL or more for certolizumab pegol (n = 120).

In the study, about three-quarters of the patients were women. The mean age was 58 years, and disease duration was just under 6 years. Most patients were starting their first biologic.

The crude rate of all infections at 1 year, including recurrent infections, was 464 per 1,000 patient-years in the high biologic drug level group versus 314 per 1,000 patient-years in the low biologic drug level group. When only the first infections were considered, the crude rate of all infections within the first year were a respective 300 and 229 per 1,000 patient-years, with an adjusted hazard ratio of 1.27, Dr. Jani reported.

As expected, lower respiratory tract infections were the most common type of infection, occurring in 34% of patients with high drug levels versus around 10% in the low drug level group. Upper respiratory tract, urinary tract, and skin infections including shingles were seen in a respective 16%, 15%, and 8% in the high drug level group, with rates less than 5% in the low drug level group.

Of note, there were certain types of infections present in the high but not low drug level groups: bacterial peritonitis, neutropenic sepsis, and herpes zoster.

Crude rates for serious infections at 1 year were 76 and 54 per 1,000 patient-years, respectively, for the high and low drug level groups. The crude rates for the first serious infection within the first year were 44 and 29 per 1,000 patient-years. The adjusted hazard ratio for the risk of serious infection at 1 year was 1.26. Serious infections were rare events, Dr. Jani emphasized, so the power was reduced, but “there was a slightly increased risk.”

Aside from the low statistical power to assess the rarer serious infections, another limitation was that drug levels were not measured at the time of the adverse event.

Concluding, Dr. Jani suggested that perhaps monitoring drug levels could be useful in predicting the risk of infection in patients being treated with biologics for rheumatoid arthritis.

Furthermore, “in patients with remission, dose-tapering guided by therapeutic drug monitoring may help lower infection risk and help us balance safety and efficacy.”

When asked to comment, Tore K. Kvien, MD, PhD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, supported this conclusion. “Therapeutic drug monitoring [TDM] is widely used among gastroenterologists when treating inflammatory bowel diseases with TNF inhibitors. In recent years, data from several research groups in rheumatology have indicated that TDM may help to optimize drug efficacy. The results from Dr. Jani and her colleagues also support that TDM may be important for safety. The importance of TDM as a ‘new’ hot topic in rheumatology is also supported by the recent establishment of a EULAR [European League Against Rheumatism] task force to further explore the value of TDM when treating patients with inflammatory joint diseases.”

The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These currently include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
 

SOURCE: Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.

According to the National Institute for Occupational Safety and Health (NIOSH), stress is a major problem for more than 18 million US health care workers (HCWs).¹ Increases in technology, high patient acuity, and new demands for meeting institutional benchmarks create stressful clinical work environments. HCWs at the US Department of Veterans Affairs (VA) are perhaps at particular risk of experiencing burnout due to the unique needs of VA patients and bureaucratic demands.² Stress may lead to depression, decreased job satisfaction, and other psychological distress among HCWs.³ This, in turn, affects the delivery of care. High levels of burnout have been associated with increased medication errors, lower quality of care, and lower patient satisfaction scores.^4-10

A Cochrane Review found that mental and physical relaxation reduce stress in HCWs.¹¹ Among these, meditative interventions (eg, mindfulness, meditation, yoga) have demonstrated promise.^12-14 Results from a systematic meta-analysis of meditative interventions for HCWs indicated small-to-moderate improvements in emotional exhaustion, sense of personal accomplishment, and life satisfaction. Additional research is needed to determine effects of meditative interventions on burnout and caregiver burden.¹⁵

Unfortunately, many meditative intervention programs are lengthy and require a significant investment of time. They also require some form of sitting meditation every day, placing additional demands on busy HCWs. There remains a need for practical strategies to reduce HCW stress that are easier to master and practice.

Background

We developed, implemented, evaluated, and modified an evidence-based meditative intervention called the Mantram Repetition Program (MRP) to address workplace stress and burnout. The MRP is a mind-body, spiritually enhanced intervention that offers benefits similar to other types of meditative interventions.¹⁶ MRP is composed of 3 primary components: (1) silently repeating a self-selected, meaningful word or phrase (here called a mantram); (2) intentionally slowing down thoughts and behaviors; and (3) developing the ability to focus on a single task at a time (ie, one-pointed attention). The MRP does not require participants to set aside a specific place to practice, and mantram repetition can be initiated intermittently and privately throughout the day (eg, between tasks, while walking or waiting). Examples of 4 sessions (eg, Mantram 1, 2, 3, and 4) can be found on the PsychArmor Institute website (www.psycharmor.org; San Diego, CA).

Initially, the MRP was offered in a group format, in 6 or 8 weekly, 90-minute face-to-face sessions to both patient and nonpatient populations. Studies in veterans with chronic diseases demonstrated improvements in perceived stress, anxiety, and anger, and increased levels of spiritual well-being and quality of life (QOL).^17-19 Veterans with posttraumatic stress disorder (PTSD) reported improvements in PTSD symptoms, QOL, and spiritual well-being.^20-23 Family caregivers of veterans with dementia reported significant reductions in caregiver burden, depression, and anxiety after participating in the MRP.²⁴

Similar results have substantiated the effects of the MRP among HCWs, including reductions in perceived stress, stress of conscience (ie, the conflict that results from competing values and behaviors in the workplace), and burnout.^25-27 HCWs also reported improvements in mindfulness and spiritual well-being.²⁸ In a randomized controlled trial, South Korean nurse managers who completed the MRP demonstrated significant improvements in psychosocial and spiritual well-being and leadership practice and experienced reductions in burnout compared with that of the control group.²⁷ In a qualitative study, the most frequently reported benefits of the MRP were improvements in managing symptoms of stress, anxiety, and feeling out of control.¹⁸

HCWs reported they found it difficult to attend the 8-week MRP face-to-face group classes. Therefore, we developed a shorter online version of the MRP consisting of six 1-hour educational sessions: 4 online self-learning modules, and 2 live meeting webinars with the course facilitator.²⁸ VA employees were invited to enroll in the program from June 2013 through 2016 through group e-mails and announcements in the VA Employee Education Service newsletters. Those eligible to participate could earn up to 6 hours of continuing education.

Although the program was generally well accepted, feedback from HCWs indicated that providers still lacked enough time to participate fully. We therefore condensed the MRP into one 90-minute, videotaped webinar entitled “Mind-Body-Spiritual Strategies for a Healthy Workforce: The Mantram Repetition Program.” The webinar was delivered in real time in June 2013 and archived for viewing later. This condensed course provided an overview of the development, theory, and practice of MRP core components. Specific instructions included how to choose and use a mantram; the importance of acting slowly with intention to avoid mistakes; and ways of developing single-pointed attention. Participants were invited to complete a standard course evaluation using an online survey.

This article presents results from qualitative analyses of participant feedback for the condensed MRP in a nationwide sample of more than 1,700 HCWs within the VA. We used template summary analysis to identify themes in participants’ responses to 2 open-ended questions: “What about this learning activity was most useful to you?” and “What about this learning activity was least useful to you?” These results have implications for reducing HCW stress and developing training programs for HCWs.

Analysis

Responses to the what was most useful question were downloaded to a spreadsheet file for analyses. Investigators chose summary template analysis, a rapid qualitative analytic technique, as the best strategy for analyzing these textual data. This technique is often used in health services research when it is unrealistic to use more time-consuming qualitative methods, such as coding.²⁹

To begin, the analyst, a PhD-level anthropologist, read through the feedback to identify similar words, phrases, and/or concepts (ie, themes). Once the analyst gained a sense of general themes, she developed category labels using verbatim words and/or phrases in the feedback (similar to developing in vivo codes.³⁰ She listed these categories at the top of a summary template document, providing a definition for each to ensure analytic rigor.

Next, each category was listed down the left side of the template. Participant feedback was copied and pasted from the spreadsheet form into the appropriate category for each of 200 responses. The investigator identified subthemes within each category. After analysis was completed for the first 200 course participants, the analyst grouped similar categories together into broader domains to further organize the data. She then read through the feedback from the remaining 917 course participants to identify negative cases (ie, dissimilarities in feedback). An additional researcher familiar with the condensed MRP training then examined the categories and domains. Together, they discussed and resolved any inconsistencies in interpretation of the data.

To get a better sense of the full range of perspectives about the training, the analyst then read through the written feedback for the what was least useful question. She scanned the feedback for negative cases that contradicted template findings and noted these in a document. A more balanced evaluation of the course emerged through this secondary analysis.

Results

Online surveys were completed by 1,117 participants, of which three-quarters (841) were female. Two hundred eleven (19%) viewed the condensed MRP in real time. The remaining participants viewed an online video of the course. Anonymous course evaluations captured only gender and professional classification of participants. Participants represented a wide range of professional roles. The majority (63%) held clinical positions with direct patient care. The next largest category included administrative or health information personnel (21%). There were also students and trainees among these categories.

Qualitative Findings

Feedback about the course was organized into categories during analysis: (1) instructional format; (2) mode of delivery; (3) course content; (4) professional and personal empowerment; (5) religion and spirituality; and (6) ease of mantram practice. These categories represented 2 broad domains: feedback about the course and feedback about the intervention.

Instructional Format

HCWs often reported that the most useful aspect of the course was the instructional format. Most cited the ease with which they could understand the materials and helpfulness of the examples of mantram practice. The option to download course materials for later reference was also useful. Some HCWs indicated that the course could have been improved by incorporating an experiential component in which participants paused to practice a mantram.

Mode of Delivery

Delivery mode including the convenience of the training and the flexibility of having the course available at both work and home was mentioned in the feedback. Some HCWs reported that the most useful aspect of the training was the on-demand feature, which allowed them to stop and restart the program as needed. A few, however, referenced technical difficulties with the webinar.

Content

HCWs also indicated that general information about mantram repetition and information regarding the benefits of the intervention (eg, stress reduction) were useful. The scientific basis of mantram was described as useful by some, though others reported it as least useful. Practical guidance regarding the appropriate time and place to practice a mantram as well as concrete information regarding how to select a mantram was mentioned as the most useful by other participants.

Professional and Personal Empowerment

Professional and personal empowerment was referenced in evaluations. Professional development, such as learning a strategy for enhancing work performance, was reported as positive. HCWs also reported that learning a new strategy for self-care and coping with stress was useful. Some described having experienced a sense of validation by participating in the course that was empowering. Finally, some HCWs indicated the personal growth experienced as the most useful.

Religion and Spirituality

General statements regarding the utility of having learned a spiritually-based practice that crossed religious boundaries as well as general references to the power of prayer were listed in the feedback. Other HCWs indicated the usefulness of having learned that a mantram could be secular.

Ease of Mantram

HCWs referenced the ease with which a mantram can be learned and/or practiced. Course participants described the simplicity of mantram repetition and referenced its portability (ie, it can be practiced in many different settings). Finally, the overall flexibility of mantram practice of where and when it can be performed was also described as useful.

Discussion

Qualitative feedback from participant evaluations of a 90-minute, virtual online MRP course suggests that HCWs representing all areas of care are interested in learning practical strategies for managing workplace stress. Participants overwhelmingly perceived mantram practice as feasible to implement, with the portability of mantram repetition described as particularly useful. This aspect of mantram repetition represents a distinct advantage over meditative interventions that require a dedicated space and time in which to practice (eg, yoga postures, sitting meditation).

These preliminary findings also suggest that mantram practice is acceptable to HCWs representing a variety of roles. Participants indicated that they valued learning a meditative practice that can be interpreted as spiritual or secular, depending on the word or phrase chosen. Only 1 participant reported that the practice of mantram conflicted with his/her personal beliefs. A small minority of participants who found the discussion of spirituality disconcerting nevertheless indicated that the intervention was acceptable to them.

The finding that even a 90-minute course was challenging for some HCWs to accommodate speaks to the importance of developing short-duration stress-reduction programs. The standardized Mindfulness Based Stress Reduction (MBSR) program consists of 8 weekly 2.5-hour sessions and a full-day retreat for an overall commitment of 29 to 33 hours.³¹ Additionally, a systematic review of meditative interventions for informal and professional caregivers found that programs ranged from 4 to 8 weeks.¹⁵ These lengthier programs are likely more challenging than the condensed MRP.

These results also suggest the importance of general guidelines for meditative intervention courses for reducing HCW stress. The mode of delivery should be as flexible as possible, allowing course participants to start, stop, and restart the program as needed and to participate from a location most convenient to them. Although presenting evidence for clinical effectiveness is critical for establishing credibility, statistical data should be briefly summarized. An experiential component in which participants are encouraged to practice the intervention will enhance learning and ensure the translation of knowledge into practice. Finally, framing meditative practices as compatible with many different faiths and/or secular will enhance their acceptability.

Three recommended components of an overall strategy for reducing occupational burnout in health care settings include modifying the organizational structure and work processes, improving the fit between the organization and HCWs, and promoting and allowing time for individuals to learn strategies for coping with work-related stress.³² This 90-minute online MRP course represents an aspect of an overall strategy to reduce HCW stress and burnout. Providing opportunities for HCWs to learn strategies for managing stress could enhance the quality of care and improve patient outcomes. Future pragmatic trials could determine whether mantram practice impacts clinical care at the VA and elsewhere.

Limitations

All participants were self-selected; therefore, the findings may be biased favorably toward the intervention. These qualitative analyses are not generalizable. HCWs in other, non-VA settings might have different needs and/or stressors that should be considered in future program development. If this intervention is offered to a wider audience, then other formats ought to be offered, such as print, at-home recordings, live meeting, and face-to-face.

Conclusion

Course participants reported that the condensed 90-minute virtual MRP was convenient to complete. They described the intervention as flexible and easy to learn. Participants indicated that they intended to implement what they learned in the course to reduce work-related stress. This feedback can be used to recommend guidelines for developing meditative interventions aimed at reducing stress in HCWs.

Acknowledgments
This material is based on work supported by the US Department of Veterans Affairs (VA), VA Employee Education Service and with resources from the VA San Diego Healthcare System and the VA Center for Mental Healthcare & Outcomes Research, South Central Mental Illness Research, Education, and Clinical Center at the Central Arkansas Veterans Healthcare System.

According to the National Institute for Occupational Safety and Health (NIOSH), stress is a major problem for more than 18 million US health care workers (HCWs).¹ Increases in technology, high patient acuity, and new demands for meeting institutional benchmarks create stressful clinical work environments. HCWs at the US Department of Veterans Affairs (VA) are perhaps at particular risk of experiencing burnout due to the unique needs of VA patients and bureaucratic demands.² Stress may lead to depression, decreased job satisfaction, and other psychological distress among HCWs.³ This, in turn, affects the delivery of care. High levels of burnout have been associated with increased medication errors, lower quality of care, and lower patient satisfaction scores.^4-10

A Cochrane Review found that mental and physical relaxation reduce stress in HCWs.¹¹ Among these, meditative interventions (eg, mindfulness, meditation, yoga) have demonstrated promise.^12-14 Results from a systematic meta-analysis of meditative interventions for HCWs indicated small-to-moderate improvements in emotional exhaustion, sense of personal accomplishment, and life satisfaction. Additional research is needed to determine effects of meditative interventions on burnout and caregiver burden.¹⁵

Unfortunately, many meditative intervention programs are lengthy and require a significant investment of time. They also require some form of sitting meditation every day, placing additional demands on busy HCWs. There remains a need for practical strategies to reduce HCW stress that are easier to master and practice.

Background

We developed, implemented, evaluated, and modified an evidence-based meditative intervention called the Mantram Repetition Program (MRP) to address workplace stress and burnout. The MRP is a mind-body, spiritually enhanced intervention that offers benefits similar to other types of meditative interventions.¹⁶ MRP is composed of 3 primary components: (1) silently repeating a self-selected, meaningful word or phrase (here called a mantram); (2) intentionally slowing down thoughts and behaviors; and (3) developing the ability to focus on a single task at a time (ie, one-pointed attention). The MRP does not require participants to set aside a specific place to practice, and mantram repetition can be initiated intermittently and privately throughout the day (eg, between tasks, while walking or waiting). Examples of 4 sessions (eg, Mantram 1, 2, 3, and 4) can be found on the PsychArmor Institute website (www.psycharmor.org; San Diego, CA).

Initially, the MRP was offered in a group format, in 6 or 8 weekly, 90-minute face-to-face sessions to both patient and nonpatient populations. Studies in veterans with chronic diseases demonstrated improvements in perceived stress, anxiety, and anger, and increased levels of spiritual well-being and quality of life (QOL).^17-19 Veterans with posttraumatic stress disorder (PTSD) reported improvements in PTSD symptoms, QOL, and spiritual well-being.^20-23 Family caregivers of veterans with dementia reported significant reductions in caregiver burden, depression, and anxiety after participating in the MRP.²⁴

Similar results have substantiated the effects of the MRP among HCWs, including reductions in perceived stress, stress of conscience (ie, the conflict that results from competing values and behaviors in the workplace), and burnout.^25-27 HCWs also reported improvements in mindfulness and spiritual well-being.²⁸ In a randomized controlled trial, South Korean nurse managers who completed the MRP demonstrated significant improvements in psychosocial and spiritual well-being and leadership practice and experienced reductions in burnout compared with that of the control group.²⁷ In a qualitative study, the most frequently reported benefits of the MRP were improvements in managing symptoms of stress, anxiety, and feeling out of control.¹⁸

HCWs reported they found it difficult to attend the 8-week MRP face-to-face group classes. Therefore, we developed a shorter online version of the MRP consisting of six 1-hour educational sessions: 4 online self-learning modules, and 2 live meeting webinars with the course facilitator.²⁸ VA employees were invited to enroll in the program from June 2013 through 2016 through group e-mails and announcements in the VA Employee Education Service newsletters. Those eligible to participate could earn up to 6 hours of continuing education.

Although the program was generally well accepted, feedback from HCWs indicated that providers still lacked enough time to participate fully. We therefore condensed the MRP into one 90-minute, videotaped webinar entitled “Mind-Body-Spiritual Strategies for a Healthy Workforce: The Mantram Repetition Program.” The webinar was delivered in real time in June 2013 and archived for viewing later. This condensed course provided an overview of the development, theory, and practice of MRP core components. Specific instructions included how to choose and use a mantram; the importance of acting slowly with intention to avoid mistakes; and ways of developing single-pointed attention. Participants were invited to complete a standard course evaluation using an online survey.

This article presents results from qualitative analyses of participant feedback for the condensed MRP in a nationwide sample of more than 1,700 HCWs within the VA. We used template summary analysis to identify themes in participants’ responses to 2 open-ended questions: “What about this learning activity was most useful to you?” and “What about this learning activity was least useful to you?” These results have implications for reducing HCW stress and developing training programs for HCWs.

Analysis

Responses to the what was most useful question were downloaded to a spreadsheet file for analyses. Investigators chose summary template analysis, a rapid qualitative analytic technique, as the best strategy for analyzing these textual data. This technique is often used in health services research when it is unrealistic to use more time-consuming qualitative methods, such as coding.²⁹

To begin, the analyst, a PhD-level anthropologist, read through the feedback to identify similar words, phrases, and/or concepts (ie, themes). Once the analyst gained a sense of general themes, she developed category labels using verbatim words and/or phrases in the feedback (similar to developing in vivo codes.³⁰ She listed these categories at the top of a summary template document, providing a definition for each to ensure analytic rigor.

Next, each category was listed down the left side of the template. Participant feedback was copied and pasted from the spreadsheet form into the appropriate category for each of 200 responses. The investigator identified subthemes within each category. After analysis was completed for the first 200 course participants, the analyst grouped similar categories together into broader domains to further organize the data. She then read through the feedback from the remaining 917 course participants to identify negative cases (ie, dissimilarities in feedback). An additional researcher familiar with the condensed MRP training then examined the categories and domains. Together, they discussed and resolved any inconsistencies in interpretation of the data.

To get a better sense of the full range of perspectives about the training, the analyst then read through the written feedback for the what was least useful question. She scanned the feedback for negative cases that contradicted template findings and noted these in a document. A more balanced evaluation of the course emerged through this secondary analysis.

Results

Online surveys were completed by 1,117 participants, of which three-quarters (841) were female. Two hundred eleven (19%) viewed the condensed MRP in real time. The remaining participants viewed an online video of the course. Anonymous course evaluations captured only gender and professional classification of participants. Participants represented a wide range of professional roles. The majority (63%) held clinical positions with direct patient care. The next largest category included administrative or health information personnel (21%). There were also students and trainees among these categories.

Qualitative Findings

Feedback about the course was organized into categories during analysis: (1) instructional format; (2) mode of delivery; (3) course content; (4) professional and personal empowerment; (5) religion and spirituality; and (6) ease of mantram practice. These categories represented 2 broad domains: feedback about the course and feedback about the intervention.

Instructional Format

HCWs often reported that the most useful aspect of the course was the instructional format. Most cited the ease with which they could understand the materials and helpfulness of the examples of mantram practice. The option to download course materials for later reference was also useful. Some HCWs indicated that the course could have been improved by incorporating an experiential component in which participants paused to practice a mantram.

Mode of Delivery

Delivery mode including the convenience of the training and the flexibility of having the course available at both work and home was mentioned in the feedback. Some HCWs reported that the most useful aspect of the training was the on-demand feature, which allowed them to stop and restart the program as needed. A few, however, referenced technical difficulties with the webinar.

Content

HCWs also indicated that general information about mantram repetition and information regarding the benefits of the intervention (eg, stress reduction) were useful. The scientific basis of mantram was described as useful by some, though others reported it as least useful. Practical guidance regarding the appropriate time and place to practice a mantram as well as concrete information regarding how to select a mantram was mentioned as the most useful by other participants.

Professional and Personal Empowerment

Professional and personal empowerment was referenced in evaluations. Professional development, such as learning a strategy for enhancing work performance, was reported as positive. HCWs also reported that learning a new strategy for self-care and coping with stress was useful. Some described having experienced a sense of validation by participating in the course that was empowering. Finally, some HCWs indicated the personal growth experienced as the most useful.

Religion and Spirituality

General statements regarding the utility of having learned a spiritually-based practice that crossed religious boundaries as well as general references to the power of prayer were listed in the feedback. Other HCWs indicated the usefulness of having learned that a mantram could be secular.

Ease of Mantram

HCWs referenced the ease with which a mantram can be learned and/or practiced. Course participants described the simplicity of mantram repetition and referenced its portability (ie, it can be practiced in many different settings). Finally, the overall flexibility of mantram practice of where and when it can be performed was also described as useful.

Discussion

Qualitative feedback from participant evaluations of a 90-minute, virtual online MRP course suggests that HCWs representing all areas of care are interested in learning practical strategies for managing workplace stress. Participants overwhelmingly perceived mantram practice as feasible to implement, with the portability of mantram repetition described as particularly useful. This aspect of mantram repetition represents a distinct advantage over meditative interventions that require a dedicated space and time in which to practice (eg, yoga postures, sitting meditation).

These preliminary findings also suggest that mantram practice is acceptable to HCWs representing a variety of roles. Participants indicated that they valued learning a meditative practice that can be interpreted as spiritual or secular, depending on the word or phrase chosen. Only 1 participant reported that the practice of mantram conflicted with his/her personal beliefs. A small minority of participants who found the discussion of spirituality disconcerting nevertheless indicated that the intervention was acceptable to them.

The finding that even a 90-minute course was challenging for some HCWs to accommodate speaks to the importance of developing short-duration stress-reduction programs. The standardized Mindfulness Based Stress Reduction (MBSR) program consists of 8 weekly 2.5-hour sessions and a full-day retreat for an overall commitment of 29 to 33 hours.³¹ Additionally, a systematic review of meditative interventions for informal and professional caregivers found that programs ranged from 4 to 8 weeks.¹⁵ These lengthier programs are likely more challenging than the condensed MRP.

These results also suggest the importance of general guidelines for meditative intervention courses for reducing HCW stress. The mode of delivery should be as flexible as possible, allowing course participants to start, stop, and restart the program as needed and to participate from a location most convenient to them. Although presenting evidence for clinical effectiveness is critical for establishing credibility, statistical data should be briefly summarized. An experiential component in which participants are encouraged to practice the intervention will enhance learning and ensure the translation of knowledge into practice. Finally, framing meditative practices as compatible with many different faiths and/or secular will enhance their acceptability.

Three recommended components of an overall strategy for reducing occupational burnout in health care settings include modifying the organizational structure and work processes, improving the fit between the organization and HCWs, and promoting and allowing time for individuals to learn strategies for coping with work-related stress.³² This 90-minute online MRP course represents an aspect of an overall strategy to reduce HCW stress and burnout. Providing opportunities for HCWs to learn strategies for managing stress could enhance the quality of care and improve patient outcomes. Future pragmatic trials could determine whether mantram practice impacts clinical care at the VA and elsewhere.

Limitations

All participants were self-selected; therefore, the findings may be biased favorably toward the intervention. These qualitative analyses are not generalizable. HCWs in other, non-VA settings might have different needs and/or stressors that should be considered in future program development. If this intervention is offered to a wider audience, then other formats ought to be offered, such as print, at-home recordings, live meeting, and face-to-face.

Conclusion

Course participants reported that the condensed 90-minute virtual MRP was convenient to complete. They described the intervention as flexible and easy to learn. Participants indicated that they intended to implement what they learned in the course to reduce work-related stress. This feedback can be used to recommend guidelines for developing meditative interventions aimed at reducing stress in HCWs.

Acknowledgments
This material is based on work supported by the US Department of Veterans Affairs (VA), VA Employee Education Service and with resources from the VA San Diego Healthcare System and the VA Center for Mental Healthcare & Outcomes Research, South Central Mental Illness Research, Education, and Clinical Center at the Central Arkansas Veterans Healthcare System.

According to the National Institute for Occupational Safety and Health (NIOSH), stress is a major problem for more than 18 million US health care workers (HCWs).¹ Increases in technology, high patient acuity, and new demands for meeting institutional benchmarks create stressful clinical work environments. HCWs at the US Department of Veterans Affairs (VA) are perhaps at particular risk of experiencing burnout due to the unique needs of VA patients and bureaucratic demands.² Stress may lead to depression, decreased job satisfaction, and other psychological distress among HCWs.³ This, in turn, affects the delivery of care. High levels of burnout have been associated with increased medication errors, lower quality of care, and lower patient satisfaction scores.^4-10

A Cochrane Review found that mental and physical relaxation reduce stress in HCWs.¹¹ Among these, meditative interventions (eg, mindfulness, meditation, yoga) have demonstrated promise.^12-14 Results from a systematic meta-analysis of meditative interventions for HCWs indicated small-to-moderate improvements in emotional exhaustion, sense of personal accomplishment, and life satisfaction. Additional research is needed to determine effects of meditative interventions on burnout and caregiver burden.¹⁵

Unfortunately, many meditative intervention programs are lengthy and require a significant investment of time. They also require some form of sitting meditation every day, placing additional demands on busy HCWs. There remains a need for practical strategies to reduce HCW stress that are easier to master and practice.

Background

We developed, implemented, evaluated, and modified an evidence-based meditative intervention called the Mantram Repetition Program (MRP) to address workplace stress and burnout. The MRP is a mind-body, spiritually enhanced intervention that offers benefits similar to other types of meditative interventions.¹⁶ MRP is composed of 3 primary components: (1) silently repeating a self-selected, meaningful word or phrase (here called a mantram); (2) intentionally slowing down thoughts and behaviors; and (3) developing the ability to focus on a single task at a time (ie, one-pointed attention). The MRP does not require participants to set aside a specific place to practice, and mantram repetition can be initiated intermittently and privately throughout the day (eg, between tasks, while walking or waiting). Examples of 4 sessions (eg, Mantram 1, 2, 3, and 4) can be found on the PsychArmor Institute website (www.psycharmor.org; San Diego, CA).

Initially, the MRP was offered in a group format, in 6 or 8 weekly, 90-minute face-to-face sessions to both patient and nonpatient populations. Studies in veterans with chronic diseases demonstrated improvements in perceived stress, anxiety, and anger, and increased levels of spiritual well-being and quality of life (QOL).^17-19 Veterans with posttraumatic stress disorder (PTSD) reported improvements in PTSD symptoms, QOL, and spiritual well-being.^20-23 Family caregivers of veterans with dementia reported significant reductions in caregiver burden, depression, and anxiety after participating in the MRP.²⁴

Similar results have substantiated the effects of the MRP among HCWs, including reductions in perceived stress, stress of conscience (ie, the conflict that results from competing values and behaviors in the workplace), and burnout.^25-27 HCWs also reported improvements in mindfulness and spiritual well-being.²⁸ In a randomized controlled trial, South Korean nurse managers who completed the MRP demonstrated significant improvements in psychosocial and spiritual well-being and leadership practice and experienced reductions in burnout compared with that of the control group.²⁷ In a qualitative study, the most frequently reported benefits of the MRP were improvements in managing symptoms of stress, anxiety, and feeling out of control.¹⁸

HCWs reported they found it difficult to attend the 8-week MRP face-to-face group classes. Therefore, we developed a shorter online version of the MRP consisting of six 1-hour educational sessions: 4 online self-learning modules, and 2 live meeting webinars with the course facilitator.²⁸ VA employees were invited to enroll in the program from June 2013 through 2016 through group e-mails and announcements in the VA Employee Education Service newsletters. Those eligible to participate could earn up to 6 hours of continuing education.

Although the program was generally well accepted, feedback from HCWs indicated that providers still lacked enough time to participate fully. We therefore condensed the MRP into one 90-minute, videotaped webinar entitled “Mind-Body-Spiritual Strategies for a Healthy Workforce: The Mantram Repetition Program.” The webinar was delivered in real time in June 2013 and archived for viewing later. This condensed course provided an overview of the development, theory, and practice of MRP core components. Specific instructions included how to choose and use a mantram; the importance of acting slowly with intention to avoid mistakes; and ways of developing single-pointed attention. Participants were invited to complete a standard course evaluation using an online survey.

This article presents results from qualitative analyses of participant feedback for the condensed MRP in a nationwide sample of more than 1,700 HCWs within the VA. We used template summary analysis to identify themes in participants’ responses to 2 open-ended questions: “What about this learning activity was most useful to you?” and “What about this learning activity was least useful to you?” These results have implications for reducing HCW stress and developing training programs for HCWs.

Analysis

Responses to the what was most useful question were downloaded to a spreadsheet file for analyses. Investigators chose summary template analysis, a rapid qualitative analytic technique, as the best strategy for analyzing these textual data. This technique is often used in health services research when it is unrealistic to use more time-consuming qualitative methods, such as coding.²⁹

To begin, the analyst, a PhD-level anthropologist, read through the feedback to identify similar words, phrases, and/or concepts (ie, themes). Once the analyst gained a sense of general themes, she developed category labels using verbatim words and/or phrases in the feedback (similar to developing in vivo codes.³⁰ She listed these categories at the top of a summary template document, providing a definition for each to ensure analytic rigor.

Next, each category was listed down the left side of the template. Participant feedback was copied and pasted from the spreadsheet form into the appropriate category for each of 200 responses. The investigator identified subthemes within each category. After analysis was completed for the first 200 course participants, the analyst grouped similar categories together into broader domains to further organize the data. She then read through the feedback from the remaining 917 course participants to identify negative cases (ie, dissimilarities in feedback). An additional researcher familiar with the condensed MRP training then examined the categories and domains. Together, they discussed and resolved any inconsistencies in interpretation of the data.

To get a better sense of the full range of perspectives about the training, the analyst then read through the written feedback for the what was least useful question. She scanned the feedback for negative cases that contradicted template findings and noted these in a document. A more balanced evaluation of the course emerged through this secondary analysis.

Results

Online surveys were completed by 1,117 participants, of which three-quarters (841) were female. Two hundred eleven (19%) viewed the condensed MRP in real time. The remaining participants viewed an online video of the course. Anonymous course evaluations captured only gender and professional classification of participants. Participants represented a wide range of professional roles. The majority (63%) held clinical positions with direct patient care. The next largest category included administrative or health information personnel (21%). There were also students and trainees among these categories.

Qualitative Findings

Feedback about the course was organized into categories during analysis: (1) instructional format; (2) mode of delivery; (3) course content; (4) professional and personal empowerment; (5) religion and spirituality; and (6) ease of mantram practice. These categories represented 2 broad domains: feedback about the course and feedback about the intervention.

Instructional Format

HCWs often reported that the most useful aspect of the course was the instructional format. Most cited the ease with which they could understand the materials and helpfulness of the examples of mantram practice. The option to download course materials for later reference was also useful. Some HCWs indicated that the course could have been improved by incorporating an experiential component in which participants paused to practice a mantram.

Mode of Delivery

Delivery mode including the convenience of the training and the flexibility of having the course available at both work and home was mentioned in the feedback. Some HCWs reported that the most useful aspect of the training was the on-demand feature, which allowed them to stop and restart the program as needed. A few, however, referenced technical difficulties with the webinar.

Content

HCWs also indicated that general information about mantram repetition and information regarding the benefits of the intervention (eg, stress reduction) were useful. The scientific basis of mantram was described as useful by some, though others reported it as least useful. Practical guidance regarding the appropriate time and place to practice a mantram as well as concrete information regarding how to select a mantram was mentioned as the most useful by other participants.

Professional and Personal Empowerment

Professional and personal empowerment was referenced in evaluations. Professional development, such as learning a strategy for enhancing work performance, was reported as positive. HCWs also reported that learning a new strategy for self-care and coping with stress was useful. Some described having experienced a sense of validation by participating in the course that was empowering. Finally, some HCWs indicated the personal growth experienced as the most useful.

Religion and Spirituality

General statements regarding the utility of having learned a spiritually-based practice that crossed religious boundaries as well as general references to the power of prayer were listed in the feedback. Other HCWs indicated the usefulness of having learned that a mantram could be secular.

Ease of Mantram

HCWs referenced the ease with which a mantram can be learned and/or practiced. Course participants described the simplicity of mantram repetition and referenced its portability (ie, it can be practiced in many different settings). Finally, the overall flexibility of mantram practice of where and when it can be performed was also described as useful.

Discussion

Qualitative feedback from participant evaluations of a 90-minute, virtual online MRP course suggests that HCWs representing all areas of care are interested in learning practical strategies for managing workplace stress. Participants overwhelmingly perceived mantram practice as feasible to implement, with the portability of mantram repetition described as particularly useful. This aspect of mantram repetition represents a distinct advantage over meditative interventions that require a dedicated space and time in which to practice (eg, yoga postures, sitting meditation).

These preliminary findings also suggest that mantram practice is acceptable to HCWs representing a variety of roles. Participants indicated that they valued learning a meditative practice that can be interpreted as spiritual or secular, depending on the word or phrase chosen. Only 1 participant reported that the practice of mantram conflicted with his/her personal beliefs. A small minority of participants who found the discussion of spirituality disconcerting nevertheless indicated that the intervention was acceptable to them.

The finding that even a 90-minute course was challenging for some HCWs to accommodate speaks to the importance of developing short-duration stress-reduction programs. The standardized Mindfulness Based Stress Reduction (MBSR) program consists of 8 weekly 2.5-hour sessions and a full-day retreat for an overall commitment of 29 to 33 hours.³¹ Additionally, a systematic review of meditative interventions for informal and professional caregivers found that programs ranged from 4 to 8 weeks.¹⁵ These lengthier programs are likely more challenging than the condensed MRP.

These results also suggest the importance of general guidelines for meditative intervention courses for reducing HCW stress. The mode of delivery should be as flexible as possible, allowing course participants to start, stop, and restart the program as needed and to participate from a location most convenient to them. Although presenting evidence for clinical effectiveness is critical for establishing credibility, statistical data should be briefly summarized. An experiential component in which participants are encouraged to practice the intervention will enhance learning and ensure the translation of knowledge into practice. Finally, framing meditative practices as compatible with many different faiths and/or secular will enhance their acceptability.

Three recommended components of an overall strategy for reducing occupational burnout in health care settings include modifying the organizational structure and work processes, improving the fit between the organization and HCWs, and promoting and allowing time for individuals to learn strategies for coping with work-related stress.³² This 90-minute online MRP course represents an aspect of an overall strategy to reduce HCW stress and burnout. Providing opportunities for HCWs to learn strategies for managing stress could enhance the quality of care and improve patient outcomes. Future pragmatic trials could determine whether mantram practice impacts clinical care at the VA and elsewhere.

Limitations

All participants were self-selected; therefore, the findings may be biased favorably toward the intervention. These qualitative analyses are not generalizable. HCWs in other, non-VA settings might have different needs and/or stressors that should be considered in future program development. If this intervention is offered to a wider audience, then other formats ought to be offered, such as print, at-home recordings, live meeting, and face-to-face.

Conclusion

Course participants reported that the condensed 90-minute virtual MRP was convenient to complete. They described the intervention as flexible and easy to learn. Participants indicated that they intended to implement what they learned in the course to reduce work-related stress. This feedback can be used to recommend guidelines for developing meditative interventions aimed at reducing stress in HCWs.

Acknowledgments
This material is based on work supported by the US Department of Veterans Affairs (VA), VA Employee Education Service and with resources from the VA San Diego Healthcare System and the VA Center for Mental Healthcare & Outcomes Research, South Central Mental Illness Research, Education, and Clinical Center at the Central Arkansas Veterans Healthcare System.

US Department of Veterans Affairs (VA) Community Living Centers (CLCs) provide a dynamic array of long- and short-term health and rehabilitative services in a person-centered environment designed to meet the individual needs of veteran residents. The VA Office of Geriatrics and Extended Care (GEC) manages CLCs as part of its commitment to “optimizing the health and well-being of veterans with multiple chronic conditions, life-limiting illness, frailty or disability associated with chronic disease, aging or injury.”¹

CLCs are home to veterans who require short stays before going home, as well as those who require longer or permanent domicile. CLCs also are home to several special populations of veterans, including those with spinal cord injury and those who choose palliative or hospice care. CLCs have embraced cultural transformation, creating therapeutic environments that function as real homes, with the kitchen at the center, and daily activities scheduled around the veterans’ preferences. Data about CLC quality are now available to the public, highlighting the important role of support for and continual refinement to quality improvement (QI) processes in the CLC system. ^2,3

CONCERT Program

High-functioning teams are critical to achieving improvement in such processes.⁴ In fiscal year (FY) 2017, GEC launched a national center to engage and support CLC staff in creating high-functioning, relationship-based teams through specific QI practices, thereby aiming to improve veteran experience and quality of care. The center, known as the CLCs’ Ongoing National Center for Enhancing Resources and Training (CONCERT), is based on extensive VA-funded research in CLCs^5-7 and builds on existing, evidence-based literature emphasizing the importance of strengths-based learning, collaborative problem solving, and structured observation.^8-13 The CONCERT mission is to support CLCs in ongoing QI efforts, providing guidance, training, and resources. This article summarizes the previous research on which CONCERT is based and describes its current activities, which focus on implementing a national team-based quality improvement initiative.

Earlier VA-funded CLC research included a VA Office of Patient Centered Care and Cultural Transformation local innovation project and 2 VA Office of Research and Development-funded research studies. The local innovation project focused on strengthening staff leadership and relational skills in 1 CLC by engaging leaders and staff in collaborative work to reduce stress. The goal was to build high-functioning team skills through shared projects that created positive work experiences and reduced job-related stress while also improving veteran experience and quality of care.^14,15 Over the course of a year, 2 national consultants in nursing home quality improvement worked with CLC leadership and staff, including conducting nine 4-day site visits. Using an approach designed to foster development of high-functioning teams, individual CLC neighborhoods (ie, units) developed and implemented neighborhood-initiated, neighborhood-based pilot projects, such as an individualized finger foods dining option for residents with dementia who became distressed when sitting at a table during a meal. Outcomes of these projects included improved staff communication and staff satisfaction, particularly psychological safety.

In the concurrently conducted pilot research study, a research team comprehensively assessed the person-centered care efforts of 3 CLCs prior to their construction of Green House-type (small house) homes. This mixed-methods study included more than 50 qualitative interviews conducted with VA medical center leadership and CLC staff and residents. Researchers also administered online employee surveys and conducted site visits, including more than 60 hours of direct observation of CLC life and team functioning. The local institutional review boards approved all study procedures, and researchers notified local unions.

Analyses highlighted 2 important aspects of person-centered care not captured by then-existing measurement instruments: the type, quality, and number of staff/resident interactions and the type, quality, and level of resident engagement. The team therefore developed a structured, systematic, observation-based instrument to measure these concepts.⁵ But while researchers found this instrument useful, it was too complex to be used by CLC staff for QI.

LOCK Quality Improvement

A later and larger research study addressed this issue. In the study, researchers worked with CLC staff to convert the complex observation-based research instrument into several structured tools that were easier for CLC staff to use.⁶ The researchers then incorporated their experience with the prior local innovation project and designed and implemented a QI program, which operationalized an evidence-based bundle of practices to implement the new tools in 6 CLCs. Researchers called the bundle of practices “LOCK”: (1) Learn from the bright spots; (2) Observe; (3) Collaborate in huddles; and (4) Keep it bite-sized.

Learn from the bright spots. Studies on strengths-based learning indicate that recognizing and sharing positive instances of ideal practice helps provide clear direction regarding what needs to be done differently to achieve success. Identifying and learning from outlying instances of successful practice encourages staff to continue those behaviors and gives staff tangible examples of how they may improve.^16-19 That is, concentrating on instances where a negative outcome was at risk of occurring but did not occur (ie, a positive outlier or “bright spot”) enables staff to analyze what facilitated the success and design and pilot strategies to replicate it.

Observe. Human factors engineering is built on the principle that integrated approaches for studying work systems can identify areas for improvement.⁸ Observation is a key tool in this approach. A recent review of 69 studies that used observation to assess clinical performance found it useful in identifying factors affecting quality and safety.⁹

Collaborate in huddles. A necessary component to overcoming barriers to successful QI is having high-functioning teams effectively coordinate work. In the theory of relational coordination, this is operationalized as high-quality interactions (frequent, timely, and accurate communication) and high-quality relationships (share knowledge, shared goals, and mutual respect).^10,11 Improved relational coordination can lead to higher quality of care outcomes and job satisfaction by enabling individuals to manage their tasks with less delay, more rapid and effective responses, fewer errors, and less wasted effort.¹²

Keep it bite-sized. Regular practice of a new behavior is one of the keys to making that new behavior part of an automatic routine (ie, a habit). To be successfully integrated into staff work routines, QI initiatives must be perceived as congruent with and easily integrated into care goals and workplace practices. Quick, focused, team-building and solution-oriented QI initiatives, therefore, have the greatest chance of success, particularly if staff feel they have little time for participating in new initiatives.¹³

Researchers designed the 4 LOCK practices to be interrelated and build on one another, creating a bundle to be used together to help facilitate positive change in resident/staff interactions and resident engagement.⁷ For 6 months, researchers studied the 6 CLCs’ use of the new structured observation tools as part of the LOCK-based QI program. The participating CLCs had such success in improving staff interactions with residents and residents’ engagement in CLC life that GEC, under the CONCERT umbrella, rolled out the LOCK bundle of practices to CLCs nationwide.²⁰

CONCERT’s current activities focus on helping CLCs implement the LOCK bundle nationwide as a relational coordination-based national QI initiative designed to improve quality of care and staff satisfaction. The CONCERT team began this implementation in FY 2017 using a train-the-trainer approach through a staggered veterans integrated service network (VISN) rollout. Each CLC sent 2 leaders to a VISN-wide training program at a host CLC site (the host site was able to have more participants attend). Afterward, the CONCERT team provided individualized phone support to help CLCs implement the program. A VA Pulse (intranet-based social media portal) site hosts all training materials, program videos, an active blog, community discussions, etc.

In FY 2018, the program shifted to a VISN-based support system, with a CONCERT team member assigned to each VISN and VISN-based webinars to facilitate information exchange, collaboration, and group learning. In FY 2018, the CONCERT team also conducted site visits to selected CLCs with strong implementation success records to learn about program facilitators and to disseminate the lessons learned. Spanning FYs 2018 and 2019, the CONCERT team also supports historically low-performing CLCs through a series of rapid-cycle learning intensives based on the Institute for Healthcare Improvement breakthrough collaborative series model for accelerated and sustained QI.²¹ These incorporate in-person or virtual learning sessions, in which participants learn about and share effective practices, and between-session learning assignments, to facilitate the piloting, implementation, and sustainment of system changes. As part of the CONCERT continuous QI process, the CONCERT team closely monitors the impact of the program and continues to pilot, adapt, and change practices as it learns more about how best to help CLCs improve.

Conclusion

A key CONCERT principle is that health care systems create health care outcomes. The CONCERT team uses the theory of relational coordination to support implementation of the LOCK bundle of practices to help CLCs change their systems to achieve high performance. Through implementation of the LOCK bundle of practices, CLC staff develop, pilot, and spread new systems for communication, teamwork, and collaborative problem solving, as well as developing skills to participate effectively in these systems. CONCERT represents just 1 way VA supports CLCs in their continual journeys toward ever-improved quality of veteran care.

Acknowledgments
The authors thank Barbara Frank and Cathie Brady for their contributions to the development of the CONCERT program.

US Department of Veterans Affairs (VA) Community Living Centers (CLCs) provide a dynamic array of long- and short-term health and rehabilitative services in a person-centered environment designed to meet the individual needs of veteran residents. The VA Office of Geriatrics and Extended Care (GEC) manages CLCs as part of its commitment to “optimizing the health and well-being of veterans with multiple chronic conditions, life-limiting illness, frailty or disability associated with chronic disease, aging or injury.”¹

CLCs are home to veterans who require short stays before going home, as well as those who require longer or permanent domicile. CLCs also are home to several special populations of veterans, including those with spinal cord injury and those who choose palliative or hospice care. CLCs have embraced cultural transformation, creating therapeutic environments that function as real homes, with the kitchen at the center, and daily activities scheduled around the veterans’ preferences. Data about CLC quality are now available to the public, highlighting the important role of support for and continual refinement to quality improvement (QI) processes in the CLC system. ^2,3

CONCERT Program

High-functioning teams are critical to achieving improvement in such processes.⁴ In fiscal year (FY) 2017, GEC launched a national center to engage and support CLC staff in creating high-functioning, relationship-based teams through specific QI practices, thereby aiming to improve veteran experience and quality of care. The center, known as the CLCs’ Ongoing National Center for Enhancing Resources and Training (CONCERT), is based on extensive VA-funded research in CLCs^5-7 and builds on existing, evidence-based literature emphasizing the importance of strengths-based learning, collaborative problem solving, and structured observation.^8-13 The CONCERT mission is to support CLCs in ongoing QI efforts, providing guidance, training, and resources. This article summarizes the previous research on which CONCERT is based and describes its current activities, which focus on implementing a national team-based quality improvement initiative.

Earlier VA-funded CLC research included a VA Office of Patient Centered Care and Cultural Transformation local innovation project and 2 VA Office of Research and Development-funded research studies. The local innovation project focused on strengthening staff leadership and relational skills in 1 CLC by engaging leaders and staff in collaborative work to reduce stress. The goal was to build high-functioning team skills through shared projects that created positive work experiences and reduced job-related stress while also improving veteran experience and quality of care.^14,15 Over the course of a year, 2 national consultants in nursing home quality improvement worked with CLC leadership and staff, including conducting nine 4-day site visits. Using an approach designed to foster development of high-functioning teams, individual CLC neighborhoods (ie, units) developed and implemented neighborhood-initiated, neighborhood-based pilot projects, such as an individualized finger foods dining option for residents with dementia who became distressed when sitting at a table during a meal. Outcomes of these projects included improved staff communication and staff satisfaction, particularly psychological safety.

In the concurrently conducted pilot research study, a research team comprehensively assessed the person-centered care efforts of 3 CLCs prior to their construction of Green House-type (small house) homes. This mixed-methods study included more than 50 qualitative interviews conducted with VA medical center leadership and CLC staff and residents. Researchers also administered online employee surveys and conducted site visits, including more than 60 hours of direct observation of CLC life and team functioning. The local institutional review boards approved all study procedures, and researchers notified local unions.

Analyses highlighted 2 important aspects of person-centered care not captured by then-existing measurement instruments: the type, quality, and number of staff/resident interactions and the type, quality, and level of resident engagement. The team therefore developed a structured, systematic, observation-based instrument to measure these concepts.⁵ But while researchers found this instrument useful, it was too complex to be used by CLC staff for QI.

LOCK Quality Improvement

A later and larger research study addressed this issue. In the study, researchers worked with CLC staff to convert the complex observation-based research instrument into several structured tools that were easier for CLC staff to use.⁶ The researchers then incorporated their experience with the prior local innovation project and designed and implemented a QI program, which operationalized an evidence-based bundle of practices to implement the new tools in 6 CLCs. Researchers called the bundle of practices “LOCK”: (1) Learn from the bright spots; (2) Observe; (3) Collaborate in huddles; and (4) Keep it bite-sized.

Learn from the bright spots. Studies on strengths-based learning indicate that recognizing and sharing positive instances of ideal practice helps provide clear direction regarding what needs to be done differently to achieve success. Identifying and learning from outlying instances of successful practice encourages staff to continue those behaviors and gives staff tangible examples of how they may improve.^16-19 That is, concentrating on instances where a negative outcome was at risk of occurring but did not occur (ie, a positive outlier or “bright spot”) enables staff to analyze what facilitated the success and design and pilot strategies to replicate it.

Observe. Human factors engineering is built on the principle that integrated approaches for studying work systems can identify areas for improvement.⁸ Observation is a key tool in this approach. A recent review of 69 studies that used observation to assess clinical performance found it useful in identifying factors affecting quality and safety.⁹

Collaborate in huddles. A necessary component to overcoming barriers to successful QI is having high-functioning teams effectively coordinate work. In the theory of relational coordination, this is operationalized as high-quality interactions (frequent, timely, and accurate communication) and high-quality relationships (share knowledge, shared goals, and mutual respect).^10,11 Improved relational coordination can lead to higher quality of care outcomes and job satisfaction by enabling individuals to manage their tasks with less delay, more rapid and effective responses, fewer errors, and less wasted effort.¹²

Keep it bite-sized. Regular practice of a new behavior is one of the keys to making that new behavior part of an automatic routine (ie, a habit). To be successfully integrated into staff work routines, QI initiatives must be perceived as congruent with and easily integrated into care goals and workplace practices. Quick, focused, team-building and solution-oriented QI initiatives, therefore, have the greatest chance of success, particularly if staff feel they have little time for participating in new initiatives.¹³

Researchers designed the 4 LOCK practices to be interrelated and build on one another, creating a bundle to be used together to help facilitate positive change in resident/staff interactions and resident engagement.⁷ For 6 months, researchers studied the 6 CLCs’ use of the new structured observation tools as part of the LOCK-based QI program. The participating CLCs had such success in improving staff interactions with residents and residents’ engagement in CLC life that GEC, under the CONCERT umbrella, rolled out the LOCK bundle of practices to CLCs nationwide.²⁰

CONCERT’s current activities focus on helping CLCs implement the LOCK bundle nationwide as a relational coordination-based national QI initiative designed to improve quality of care and staff satisfaction. The CONCERT team began this implementation in FY 2017 using a train-the-trainer approach through a staggered veterans integrated service network (VISN) rollout. Each CLC sent 2 leaders to a VISN-wide training program at a host CLC site (the host site was able to have more participants attend). Afterward, the CONCERT team provided individualized phone support to help CLCs implement the program. A VA Pulse (intranet-based social media portal) site hosts all training materials, program videos, an active blog, community discussions, etc.

In FY 2018, the program shifted to a VISN-based support system, with a CONCERT team member assigned to each VISN and VISN-based webinars to facilitate information exchange, collaboration, and group learning. In FY 2018, the CONCERT team also conducted site visits to selected CLCs with strong implementation success records to learn about program facilitators and to disseminate the lessons learned. Spanning FYs 2018 and 2019, the CONCERT team also supports historically low-performing CLCs through a series of rapid-cycle learning intensives based on the Institute for Healthcare Improvement breakthrough collaborative series model for accelerated and sustained QI.²¹ These incorporate in-person or virtual learning sessions, in which participants learn about and share effective practices, and between-session learning assignments, to facilitate the piloting, implementation, and sustainment of system changes. As part of the CONCERT continuous QI process, the CONCERT team closely monitors the impact of the program and continues to pilot, adapt, and change practices as it learns more about how best to help CLCs improve.

Conclusion

A key CONCERT principle is that health care systems create health care outcomes. The CONCERT team uses the theory of relational coordination to support implementation of the LOCK bundle of practices to help CLCs change their systems to achieve high performance. Through implementation of the LOCK bundle of practices, CLC staff develop, pilot, and spread new systems for communication, teamwork, and collaborative problem solving, as well as developing skills to participate effectively in these systems. CONCERT represents just 1 way VA supports CLCs in their continual journeys toward ever-improved quality of veteran care.

Acknowledgments
The authors thank Barbara Frank and Cathie Brady for their contributions to the development of the CONCERT program.

US Department of Veterans Affairs (VA) Community Living Centers (CLCs) provide a dynamic array of long- and short-term health and rehabilitative services in a person-centered environment designed to meet the individual needs of veteran residents. The VA Office of Geriatrics and Extended Care (GEC) manages CLCs as part of its commitment to “optimizing the health and well-being of veterans with multiple chronic conditions, life-limiting illness, frailty or disability associated with chronic disease, aging or injury.”¹

CLCs are home to veterans who require short stays before going home, as well as those who require longer or permanent domicile. CLCs also are home to several special populations of veterans, including those with spinal cord injury and those who choose palliative or hospice care. CLCs have embraced cultural transformation, creating therapeutic environments that function as real homes, with the kitchen at the center, and daily activities scheduled around the veterans’ preferences. Data about CLC quality are now available to the public, highlighting the important role of support for and continual refinement to quality improvement (QI) processes in the CLC system. ^2,3

CONCERT Program

High-functioning teams are critical to achieving improvement in such processes.⁴ In fiscal year (FY) 2017, GEC launched a national center to engage and support CLC staff in creating high-functioning, relationship-based teams through specific QI practices, thereby aiming to improve veteran experience and quality of care. The center, known as the CLCs’ Ongoing National Center for Enhancing Resources and Training (CONCERT), is based on extensive VA-funded research in CLCs^5-7 and builds on existing, evidence-based literature emphasizing the importance of strengths-based learning, collaborative problem solving, and structured observation.^8-13 The CONCERT mission is to support CLCs in ongoing QI efforts, providing guidance, training, and resources. This article summarizes the previous research on which CONCERT is based and describes its current activities, which focus on implementing a national team-based quality improvement initiative.

Earlier VA-funded CLC research included a VA Office of Patient Centered Care and Cultural Transformation local innovation project and 2 VA Office of Research and Development-funded research studies. The local innovation project focused on strengthening staff leadership and relational skills in 1 CLC by engaging leaders and staff in collaborative work to reduce stress. The goal was to build high-functioning team skills through shared projects that created positive work experiences and reduced job-related stress while also improving veteran experience and quality of care.^14,15 Over the course of a year, 2 national consultants in nursing home quality improvement worked with CLC leadership and staff, including conducting nine 4-day site visits. Using an approach designed to foster development of high-functioning teams, individual CLC neighborhoods (ie, units) developed and implemented neighborhood-initiated, neighborhood-based pilot projects, such as an individualized finger foods dining option for residents with dementia who became distressed when sitting at a table during a meal. Outcomes of these projects included improved staff communication and staff satisfaction, particularly psychological safety.

In the concurrently conducted pilot research study, a research team comprehensively assessed the person-centered care efforts of 3 CLCs prior to their construction of Green House-type (small house) homes. This mixed-methods study included more than 50 qualitative interviews conducted with VA medical center leadership and CLC staff and residents. Researchers also administered online employee surveys and conducted site visits, including more than 60 hours of direct observation of CLC life and team functioning. The local institutional review boards approved all study procedures, and researchers notified local unions.

Analyses highlighted 2 important aspects of person-centered care not captured by then-existing measurement instruments: the type, quality, and number of staff/resident interactions and the type, quality, and level of resident engagement. The team therefore developed a structured, systematic, observation-based instrument to measure these concepts.⁵ But while researchers found this instrument useful, it was too complex to be used by CLC staff for QI.

LOCK Quality Improvement

A later and larger research study addressed this issue. In the study, researchers worked with CLC staff to convert the complex observation-based research instrument into several structured tools that were easier for CLC staff to use.⁶ The researchers then incorporated their experience with the prior local innovation project and designed and implemented a QI program, which operationalized an evidence-based bundle of practices to implement the new tools in 6 CLCs. Researchers called the bundle of practices “LOCK”: (1) Learn from the bright spots; (2) Observe; (3) Collaborate in huddles; and (4) Keep it bite-sized.

Learn from the bright spots. Studies on strengths-based learning indicate that recognizing and sharing positive instances of ideal practice helps provide clear direction regarding what needs to be done differently to achieve success. Identifying and learning from outlying instances of successful practice encourages staff to continue those behaviors and gives staff tangible examples of how they may improve.^16-19 That is, concentrating on instances where a negative outcome was at risk of occurring but did not occur (ie, a positive outlier or “bright spot”) enables staff to analyze what facilitated the success and design and pilot strategies to replicate it.

Observe. Human factors engineering is built on the principle that integrated approaches for studying work systems can identify areas for improvement.⁸ Observation is a key tool in this approach. A recent review of 69 studies that used observation to assess clinical performance found it useful in identifying factors affecting quality and safety.⁹

Collaborate in huddles. A necessary component to overcoming barriers to successful QI is having high-functioning teams effectively coordinate work. In the theory of relational coordination, this is operationalized as high-quality interactions (frequent, timely, and accurate communication) and high-quality relationships (share knowledge, shared goals, and mutual respect).^10,11 Improved relational coordination can lead to higher quality of care outcomes and job satisfaction by enabling individuals to manage their tasks with less delay, more rapid and effective responses, fewer errors, and less wasted effort.¹²

Keep it bite-sized. Regular practice of a new behavior is one of the keys to making that new behavior part of an automatic routine (ie, a habit). To be successfully integrated into staff work routines, QI initiatives must be perceived as congruent with and easily integrated into care goals and workplace practices. Quick, focused, team-building and solution-oriented QI initiatives, therefore, have the greatest chance of success, particularly if staff feel they have little time for participating in new initiatives.¹³

Researchers designed the 4 LOCK practices to be interrelated and build on one another, creating a bundle to be used together to help facilitate positive change in resident/staff interactions and resident engagement.⁷ For 6 months, researchers studied the 6 CLCs’ use of the new structured observation tools as part of the LOCK-based QI program. The participating CLCs had such success in improving staff interactions with residents and residents’ engagement in CLC life that GEC, under the CONCERT umbrella, rolled out the LOCK bundle of practices to CLCs nationwide.²⁰

CONCERT’s current activities focus on helping CLCs implement the LOCK bundle nationwide as a relational coordination-based national QI initiative designed to improve quality of care and staff satisfaction. The CONCERT team began this implementation in FY 2017 using a train-the-trainer approach through a staggered veterans integrated service network (VISN) rollout. Each CLC sent 2 leaders to a VISN-wide training program at a host CLC site (the host site was able to have more participants attend). Afterward, the CONCERT team provided individualized phone support to help CLCs implement the program. A VA Pulse (intranet-based social media portal) site hosts all training materials, program videos, an active blog, community discussions, etc.

In FY 2018, the program shifted to a VISN-based support system, with a CONCERT team member assigned to each VISN and VISN-based webinars to facilitate information exchange, collaboration, and group learning. In FY 2018, the CONCERT team also conducted site visits to selected CLCs with strong implementation success records to learn about program facilitators and to disseminate the lessons learned. Spanning FYs 2018 and 2019, the CONCERT team also supports historically low-performing CLCs through a series of rapid-cycle learning intensives based on the Institute for Healthcare Improvement breakthrough collaborative series model for accelerated and sustained QI.²¹ These incorporate in-person or virtual learning sessions, in which participants learn about and share effective practices, and between-session learning assignments, to facilitate the piloting, implementation, and sustainment of system changes. As part of the CONCERT continuous QI process, the CONCERT team closely monitors the impact of the program and continues to pilot, adapt, and change practices as it learns more about how best to help CLCs improve.

Conclusion

A key CONCERT principle is that health care systems create health care outcomes. The CONCERT team uses the theory of relational coordination to support implementation of the LOCK bundle of practices to help CLCs change their systems to achieve high performance. Through implementation of the LOCK bundle of practices, CLC staff develop, pilot, and spread new systems for communication, teamwork, and collaborative problem solving, as well as developing skills to participate effectively in these systems. CONCERT represents just 1 way VA supports CLCs in their continual journeys toward ever-improved quality of veteran care.

Acknowledgments
The authors thank Barbara Frank and Cathie Brady for their contributions to the development of the CONCERT program.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

PHILADELPHIA – The association between vitamin D insufficiency and multiple sclerosis (MS) outcome in children with acquired demyelinating syndromes (ADS) partly relates to skin pigmentation, according to research described at the annual meeting of the American Academy of Neurology. Future research will be required to understand the interactions between dietary vitamin D ingestion, sun exposure, pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and the genetic influences of vitamin D pathways with MS risk.

Race, vitamin D status, HLA-DRB1*15 genotype, and place of residence during childhood all affect the risk of MS. The place of residence also can affect exposure to ultraviolet radiation and, thus, dermal pigmentation.

Candice Dunn, a clinical research coordinator at the Children’s Hospital of Philadelphia, and colleagues conducted a prospective study to determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25[OH]D) levels measured at baseline, and skin tone are associated with MS outcome in children with ADS. They enrolled 259 children with incident ADS in a multisite study in Toronto and Philadelphia (latitudes 43° to 51°). The investigators measured non–sun-exposed upper inner arm melanin content using the DSM II ColorMeter device. They measured 25(OH)D concentrations in serum obtained within 60 days of symptom onset and compared them with laboratory-reported normative values. Vitamin D insufficiency was defined as 25(OH)D less than 75 nmol/L. Ms. Dunn and colleagues quantified HLA-DRB1*15 alleles using allele-specific polymerase chain reaction amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.

In all, 68 children were diagnosed with MS, 191 remained monophasic (monoADS). Approximately 46% of children with MS were HLA-DRB1*15-positive, compared with 29.9% of monoADS children. In addition, children with MS had significantly lower 25(OH)D levels (mean, 45.4 nmol/L) than monoADS children (mean, 61.9 nmol/L) at baseline. Non–sun-exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (mean melanin index, 46.4) and monoADS (mean melanin index, 43.5). Furthermore, 25(OH)D levels correlated with upper inner arm melanin index in the MS group, but not in children with monoADS.

Ms. Dunn had nothing to disclose, but various coauthors have received compensation from companies such as Novartis, Merck, Teva, Celgene, and Genentech.
 

[email protected]

SOURCE: Dunn C et al. AAN 2019, Abstract S19.007.

The Food and Drug Administration has approved tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) for the treatment of heart disease caused by transthyretin-mediated amyloidosis.

The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.

FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.

No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.

“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) for the treatment of heart disease caused by transthyretin-mediated amyloidosis.

The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.

FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.

No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.

“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved tafamidis meglumine (Vyndaqel) and tafamidis (Vyndamax) for the treatment of heart disease caused by transthyretin-mediated amyloidosis.

The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.

FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.

No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.

“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.

Find the full press release on the FDA website.

[email protected]

Many veterans of the Gulf War are experiencing deployment-related chronic illness, known as Gulf War illness (GWI). Symptoms of GWI include cognitive impairments (mood and memory), chronic fatigue, musculoskeletal pain, gastrointestinal (GI) disorders, respiratory problems, and skin rashes.^1-4 Three survey studies of the physical and mental health of a large cohort of Gulf War and Gulf era veterans, conducted by the US Department of Veterans Affairs (VA) Office of Public Health, established the increased prevalence of GWI in the decades that followed the end of the conflict.^5-7 Thus, GWI has become the signature adverse health-related outcome of the Gulf War. Quality improvement (QI) within the Veterans Health Administration (VHA) is needed in the diagnosis and treatment of GWI.

Background

GWI was first termed chronic multisymptom illness (CMI) by the Centers for Disease Control and Prevention (CDC). According to the CDC-10 case definition, CMI in veterans of the 1990-1991 Gulf War is defined as having ≥ 1 symptoms lasting ≥ 6 months in at least 2 of 3 categories: fatigue, depressed mood and altered cognition, and musculoskeletal pain.³ The Kansas case definition of GWI is more specific and is defined as having moderate-to-severe symptoms that are unexplained by any other diagnosis, in at least 3 of 6 categories: fatigue/sleep, somatic pain, neurologic/cognition/mood, GI, respiratory, and skin.⁴ Although chronic unexplained symptoms have occurred after other modern conflicts, the prevalence of GWI among Gulf War veterans has proven higher than those of prior conflicts.⁸

The Persian Gulf War Veterans Act of 1998 and the Veterans Programs Enhancement Act of 1998 mandated studies by the Institute of Medicine (IOM) on the biologic and chemical exposures that may have contributed to illness in the Kuwaiti theater of operations.⁹ However, elucidating the etiology and underlying pathophysiology of GWI has been a major research challenge. In the absence of objective diagnostic measures, an understanding of the fundamental pathophysiology, evidence-based treatments, a single case definition, and definitive guidelines for health care providers (HCPs) for the diagnosis and management of GWI has not been produced. As a result, veterans with GWI have struggled for nearly 3 decades to find a consistent diagnosis of and an effective treatment for their condition.

According to a report by the Government Accountability Office (GAO), the VA approved only 17% of claims for compensation for veterans with GWI from 2011 to 2015, about one-third the level of approval for all other claimed disabilities.¹⁰ Although the VA applied GAO recommendations to improve the compensation process, many veterans consider that their illness is treated as psychosomatic in clinical practice, despite emerging evidence of GWI-associated biomarkers.¹¹ Others think they have been forgotten due to their short 1-year period of service in the Gulf War.¹² To realign research, guidelines, clinical care, and the health care experience of veterans with GWI, focused QI within VHA is urgently needed.

Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) are experiencing similar CMI symptoms. A study of US Army Reserve OEF/OIF veterans found that > 60% met the CDC-10 case definition for GWI 1-year postdeployment.¹³ Thus, CMI is emerging as a serious health problem for post-9/11 veterans. The evidence of postdeployment CMI among veterans of recent conflicts underscores the need to increase efforts at a national level, beginning with the VHA. This report includes a summary of Gulf War veterans’ experiences at the Minneapolis VA Health Care System (MVAHCS) and a proposal for QI of MVAHCS processes focused on HCP education and clinical care.

Methods

To determine areas of GWI health care that needed QI at the MVAHCS, veterans with GWI were contacted for a telephone survey. These veterans had participated in the Gulf War Illness Inflammation Reduction Trial (ClinicalTrials.gov. Identifier: NCT02506192). Therefore, all met the Kansas case definition for GWI.⁴ The aim of the survey was to characterize veterans’ experiences seeking health care for chronic postdeployment symptoms.

Sixty Gulf War veterans were contacted by telephone and invited to participate in a 15-minute survey about their experience seeking diagnosis and treatment for GWI. They were informed that the survey was voluntary and confidential, that it was not part of the research trial in which they had been enrolled, and that their participation would not affect compensation received from VA. Verbal consent was requested, and 30 veterans agreed to participate in the survey.

The survey included questions about the course of illness, disability and service connection status, HCPs seen, and suggestions for improvement in their care (Table 1). 

Results

Of the 30 veterans who participated in the survey, most were male with only 2 female veterans. This proportion of female veterans (7%) is similar to the overall percentage of female veterans (6.7%) of the first Gulf War.² Ages ranged from 46 to 66 years with a mean age of 53. Mean duration of illness, defined as time elapsed since perceived onset of chronic systemic symptoms during or after deployment, was 22.8 years, with a range of 4 to 27 years. Most respondents reported symptom onset within a few years after the end of the conflict, while a few reported the onset within weeks of arriving in the Kuwaiti theater of operations. A little more than half the respondents considered themselves disabled due to their symptoms, while one-third reported losing the ability to work due to symptoms. Respondents described needing to reduce hours, retire early, or stop working altogether because of their symptoms.

Respondents attributed several common chronic symptoms to deployment in the Gulf Wars (Table 2). 

Most veterans surveyed were service connected for individual chronic symptoms. Some were service connected for systemic conditions such as fibromyalgia (FM), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS) (5 veterans were connected for each condition). Three of the 30 veterans had been diagnosed with GWI—2 by past VA physicians and 1 by a physician at a GWI research center in another state. Of those 3, only 1 was service connected for the condition. Three respondents were not service connected at all.

The most common VA HCPs seen were in primary care and neurology followed by psychiatry and psychology. Of non-VA HCPs, most respondents saw primary care providers (PCPs) followed by chiropractors (Table 4).

Before taking the Gulf War survey, a broad subjective question was posed. Respondents were asked whether VA HCPs were “supportive as you sought care for chronic postdeployment symptoms.” A majority of veterans reported that their VA HCPs were supportive. Reasons veterans gave for VA HCPs lack of support included feeling that HCPs did not believe them or trust their reported symptoms; did not care about their symptoms; refused to attribute their symptoms to Gulf War deployment; attributed symptoms to mental health issues; focused on doing things a certain way; or did not have the tools or information necessary to help.

Most non-VA HCPs were supportive. Reasons community HCPs were not supportive included “not looking at the whole picture,” not knowing veteran issues, not feeling comfortable with GWI, or not having much they could do.

Veterans were then asked whether they felt their HCPs were knowledgeable about GWI, and 13 respondents reported that their HCP was knowledgeable. Reasons respondents felt VA HCPs were not knowledgeable included denying that GWI exists, attributing symptoms to other conditions, not being aware of or familiar with GWI, needing education from the veteran, avoiding discussion about GWI or not caring to learn, or not knowing the latest research evidence to talk about GWI with authority. Compared with VA HCPs, veterans found community HCPs about half as likely to be knowledgeable about GWI. Many reported that community HCPs had not heard of GWI or had no knowledge about it.

Respondents also were asked what types of treatments they tried in order to typify the care received. The most common responses were pain medications, symptom-specific treatments, or “just putting up with it” (no treatment). Many patients were also self-medicating, trying lifestyle changes, or seeking alternative therapies.

Finally, respondents were asked on a scale of 0 (very unsatisfied) to 5 (very satisfied), how satisfied they were with their overall care at the VA. The majority were satisfied with their overall care, with two-thirds very satisfied (5 of 5) or pretty satisfied (4 of 5). Only 3 (10%) were unsatisfied or very unsatisfied. Respondents had the following comments about their care: “They treat me like I am important;” “I am very thankful even though they cannot figure it out;” “They are doing the best they can with no answers and not enough help;” “[I know] it is still a work in progress.” A number of respondents were satisfied with some HCPs or care for some but not all of their symptoms. Reasons respondents were less satisfied included desiring answers, feeling they were not respected, or feeling that their concerns were not addressed.

When asked for suggestions for improvement of GWI care, the most common response was providing up-to-date HCP education (Table 5).

Discussion

The veterans participating in this QI survey had similar demographics, symptomology, and exposures as did those in other studies.^1-7 Therefore, improvements based on their responses are likely applicable to the health care of veterans experiencing GWI-associated symptoms at other VA health care systems as well.

Veterans with GWI can lose significant functional capacity and productivity due to their symptoms. The symptoms are chronic and have afflicted many Gulf War veterans for nearly 3 decades. Furthermore, the prevalence of GWI in Gulf War veterans continues to increase.^5-7 These facts testify to the enormous health-related quality-of-life impact of GWI.

Veterans who meet the Kansas case definition for GWI were not diagnosed or service connected in a uniform manner. Only 3 of the 30 veterans in this study were given a unifying diagnosis that connected their chronic illness to Gulf War deployment. Under current guidelines, Gulf War veterans are able to receive compensation for chronic symptoms in 3 ways: (1) compensation for chronic unexplained symptoms existing for ≥ 6 months that appeared during active duty in the Southwest Asia theater or by December 31, 2021, and are ≥ 10% disabling; (2) the 1995 Persian Gulf War Veterans’ Act recognizes 3 multisymptom illnesses for which veterans can be service connected: FM, CFS, and functional GI disorders, including IBS; and (3) expansion to include any CMI of unknown etiology is underway. A uniform diagnostic protocol based on biomarkers and updated understanding of disease pathology would be helpful.

Respondents shared experiences that demonstrated perceived gaps in HCP support or knowledge. Overall, more respondents found their HCPs supportive. Many of the reasons respondents found HCPs unsupportive related to acknowledgment of symptoms. Also, more respondents found that both VA and non-VA HCPs lacked knowledge about GWI symptoms. These findings further highlight the need for HCP education within the VA and in community-based care.

The treatments tried by respondents also highlight potential areas for improvement. Most of the treatments were for pain; therefore, more involvement with pain clinics and specialists could be helpful. Symptom-specific medications also are appropriate, although only one-third of patients reported use. While medications are not necessarily markers of quality care, the fact that many patients self-medicate or go without treatment suggests that access to care could be improved. In 2014, the VA and the US Department of Defense (DoD) released the “VA/DoD Clinical Practice Guideline for the Management of Chronic Multisymptom Illness,” which recommended treatments for the global disease and specific symptoms.¹⁵

Since then, GWI research points to inflammatory and metabolic disease mechanisms.^11-14,16 As the underlying pathophysiology is further elucidated, practice guidelines will need to be updated to include anti-inflammatory and antioxidant treatments used in practice for GWI and similar chronic systemic illnesses (eg, CFS, FM, and IBS).^17-19

Randomized control trials are needed to determine the efficacy of such medications for the treatment of GWI. As new results emerge, disseminating and updating evidence-based guidelines in a coordinated manner will be required for veterans to receive appropriate treatment. Veterans also seek alternative or nonpharmaceutical interventions, such as physical therapy and diet changes. Improving access to integrative medicine, physical therapy, nutritionists, and other practitioners also could optimize veterans’ health and function.

HCP Education

The Gulf War veteran respondents who participated in the survey noted HCP education, research progress, and veteran inclusion as areas for improvement. Respondents requested dissemination of information on diagnosis and treatment of GWI for HCPs and updates on research and other actions. They suggested ways research could be more effective (such as subgrouping by exposure, which researchers have been doing) and could extend to veterans experiencing CMI from other conflicts as well.²⁰ Respondents also recommended team approaches or centers of excellence in order to receive more comprehensive care.

An asset of VHA is the culture of QI and education. The VA Employee Education System previously produced “Caring for Gulf War I Veterans,” a systemwide training module.²¹ In 2014, updated clinical practice guidelines for GWI were provided by the VA and the DoD, including evidence for each recommendation. In 2016, the VA in collaboration with the IOM produced a report summarizing conclusions and recommendations regarding associations between health concerns and Gulf War deployment.²² A concise guide for HCPs caring for veterans with GWI, updated in 2018, is available.²³ Updated treatment guidelines, based on evolving understanding of GWI pathophysiology, and continuing efforts to disseminate information will be essential.

Respondents most often presented to primary care, both within and outside of MVAHCS. Therefore, VA and community PCPs who see veterans should be equipped to recognize and diagnose GWI as well as be familiar with basic disease management and specialists whom they could refer their patients. Neurology was the second most common specialty seen by respondents. The most prominent symptoms of GWI are related to nervous system function in addition to evidence of underlying neuroinflammation.²⁰ Veterans may present to a neurologist with a variety of concerns, such as cognitive issues, sleep problems, migraines and headaches, and pain. Neurologists could best manage treatments targeting common neurologic GWI symptoms and neuroinflammation, especially as new treatments are discovered.

The next 2 most common specialty services seen were psychiatry and psychology (7 responses for each). Five respondents reported mental health issues as part of their chronic postdeployment symptoms. Population-based studies have indicated that rates of PTSD in Gulf War veterans is 3% to 6%, much lower than the prevalence of GWI.^8,20 The 2010 IOM study concluded that GWI symptoms cannot be ascribed to any known psychiatric disorder. Unfortunately, several surveyed veterans made it clear that they had been denied care due to HCPs attributing their symptoms solely to mental health issues. Therefore, psychiatrists and psychologists must be educated about GWI, mental health issues occurring in Gulf War veterans, and physiologic symptoms of GWI that may mimic or coincide with mental health issues. These HCPs also would be important to include in an interdisciplinary clinic for veterans with GWI.

Finally, respondents sought care from numerous other specialties, including gastroenterology, physical therapy, pulmonology, dermatology, and surgical subspecialties, such as orthopedics and otolaryngology. This wide range of specialists seen emphasizes the need for medical education, beginning in medical school. If provided education on GWI, these specialists would be able to treat veterans with GWI, know to look for updates on GWI management, or know to look for other common symptoms, such as chronic sinusitis in otolaryngology or recurring rashes in dermatology. We also recommend identifying HCPs in these specialties who could be part of an interdisciplinary clinic or be referrals for symptom management.

Protocol Implementation

HCP education and clinical care protocol implementation should be the initial focus of improving GWI management. A team of stakeholders within the different areas of MVAHCS, including education, HCPs, and administrative staff, will need to be developed. Reaching out to VA HCPs who have seen veterans with GWI will be an essential first step to equip them with updated education about the diagnosis and management of CMI. Providing integrated widespread education to current HCPs who are likely to encounter veterans with deployment-related CMI from the Gulf War, OND/OEF/OIF, or other deployments also will be necessary. Finally, educating medical trainees, including residents and medical students, will ensure continuous care for future veterans, post-9/11 veterans.

GWI presentations at medical grand rounds or at other medical community educational events could provide educational outlets. These events create face-to-face opportunities to discuss GWI/CMI education with HCPs, giving them the opportunity to offer feedback about their experiences and create relationships with other HCPs who have seen patients with GWI/CMI. At an educational event, a short postevent feedback form that indicates whether HCPs would like more information or get involved in a clinic for veterans with CMI could be included. This information would help identify key HCPs and areas within the local VA needing further improvements, such as creating a clinic for veterans with GWI.

Since 1946, the VA has worked with academic institutions to provide state-of-the-art health care to US veterans and train new HCPs to meet the health care needs of the nation. Every year, > 40,000 residents and 20,000 medical students receive medical training at VA facilities, making VA the largest single provider of medical education in the country. Therefore, providing detailed GWI/CMI education to medical students and residents as a standard part of the VA Talent Management System would be of value for all VA professionals.

GWI Clinics

Access to comprehensive care can be accomplished by organizing a clinic for veterans with GWI. The most likely effective location would be in primary care. PCPs who have seen veterans with GWI and/or expressed interest in learning more about GWI will be the initial point of contact. As the primary care service has connections to ancillary services, such as pharmacists, dieticians, psychologists, and social workers, organizing 1 day each week to see patients with GWI would improve care.

As the need for specialty care arises, the team also would need to identify specialists willing to receive referrals from HCPs of veterans with GWI. These specialists could be identified via feedback forms from educational events, surveys after an online educational training, or through relationships among VA physicians. As the clinic becomes established, it may be effective to have certain commonly seen specialists available in person, most likely neurology, psychiatry, gastroenterology, pulmonology, and dermatology. Also, relationships with a pain clinic, sleep medicine, and integrative medicine services should be established.

Measures of improvement in the veteran health care experience could include veterans’ perceptions of the supportiveness and knowledge of physicians about GWI as well as overall satisfaction. A follow-up survey on these measures of veterans involved in a GWI clinic and those not involved would be a way to determine whether these clinics better meet veterans’ needs and what additional QI is needed.

Conclusion

A significant number of Gulf War veterans experience chronic postdeployment symptoms that need to be better addressed. Physicians need to be equipped to recognize and manage GWI and similar postdeployment CMI among veterans of OEF/OIF/OND. We recommend creating an educational initiative about GWI among VA physicians and trainees, connecting physicians who see veterans with GWI, and establishing an interdisciplinary clinic with a referral system as the next steps to improve care for veterans. An additional goal would be to reach out to veteran networks to update them on GWI research, education, and available health care, as veterans are the essential stakeholders in the QI process.

Many veterans of the Gulf War are experiencing deployment-related chronic illness, known as Gulf War illness (GWI). Symptoms of GWI include cognitive impairments (mood and memory), chronic fatigue, musculoskeletal pain, gastrointestinal (GI) disorders, respiratory problems, and skin rashes.^1-4 Three survey studies of the physical and mental health of a large cohort of Gulf War and Gulf era veterans, conducted by the US Department of Veterans Affairs (VA) Office of Public Health, established the increased prevalence of GWI in the decades that followed the end of the conflict.^5-7 Thus, GWI has become the signature adverse health-related outcome of the Gulf War. Quality improvement (QI) within the Veterans Health Administration (VHA) is needed in the diagnosis and treatment of GWI.

Background

GWI was first termed chronic multisymptom illness (CMI) by the Centers for Disease Control and Prevention (CDC). According to the CDC-10 case definition, CMI in veterans of the 1990-1991 Gulf War is defined as having ≥ 1 symptoms lasting ≥ 6 months in at least 2 of 3 categories: fatigue, depressed mood and altered cognition, and musculoskeletal pain.³ The Kansas case definition of GWI is more specific and is defined as having moderate-to-severe symptoms that are unexplained by any other diagnosis, in at least 3 of 6 categories: fatigue/sleep, somatic pain, neurologic/cognition/mood, GI, respiratory, and skin.⁴ Although chronic unexplained symptoms have occurred after other modern conflicts, the prevalence of GWI among Gulf War veterans has proven higher than those of prior conflicts.⁸

The Persian Gulf War Veterans Act of 1998 and the Veterans Programs Enhancement Act of 1998 mandated studies by the Institute of Medicine (IOM) on the biologic and chemical exposures that may have contributed to illness in the Kuwaiti theater of operations.⁹ However, elucidating the etiology and underlying pathophysiology of GWI has been a major research challenge. In the absence of objective diagnostic measures, an understanding of the fundamental pathophysiology, evidence-based treatments, a single case definition, and definitive guidelines for health care providers (HCPs) for the diagnosis and management of GWI has not been produced. As a result, veterans with GWI have struggled for nearly 3 decades to find a consistent diagnosis of and an effective treatment for their condition.

According to a report by the Government Accountability Office (GAO), the VA approved only 17% of claims for compensation for veterans with GWI from 2011 to 2015, about one-third the level of approval for all other claimed disabilities.¹⁰ Although the VA applied GAO recommendations to improve the compensation process, many veterans consider that their illness is treated as psychosomatic in clinical practice, despite emerging evidence of GWI-associated biomarkers.¹¹ Others think they have been forgotten due to their short 1-year period of service in the Gulf War.¹² To realign research, guidelines, clinical care, and the health care experience of veterans with GWI, focused QI within VHA is urgently needed.

Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) are experiencing similar CMI symptoms. A study of US Army Reserve OEF/OIF veterans found that > 60% met the CDC-10 case definition for GWI 1-year postdeployment.¹³ Thus, CMI is emerging as a serious health problem for post-9/11 veterans. The evidence of postdeployment CMI among veterans of recent conflicts underscores the need to increase efforts at a national level, beginning with the VHA. This report includes a summary of Gulf War veterans’ experiences at the Minneapolis VA Health Care System (MVAHCS) and a proposal for QI of MVAHCS processes focused on HCP education and clinical care.

Methods

To determine areas of GWI health care that needed QI at the MVAHCS, veterans with GWI were contacted for a telephone survey. These veterans had participated in the Gulf War Illness Inflammation Reduction Trial (ClinicalTrials.gov. Identifier: NCT02506192). Therefore, all met the Kansas case definition for GWI.⁴ The aim of the survey was to characterize veterans’ experiences seeking health care for chronic postdeployment symptoms.

Sixty Gulf War veterans were contacted by telephone and invited to participate in a 15-minute survey about their experience seeking diagnosis and treatment for GWI. They were informed that the survey was voluntary and confidential, that it was not part of the research trial in which they had been enrolled, and that their participation would not affect compensation received from VA. Verbal consent was requested, and 30 veterans agreed to participate in the survey.

The survey included questions about the course of illness, disability and service connection status, HCPs seen, and suggestions for improvement in their care (Table 1). 

Results

Of the 30 veterans who participated in the survey, most were male with only 2 female veterans. This proportion of female veterans (7%) is similar to the overall percentage of female veterans (6.7%) of the first Gulf War.² Ages ranged from 46 to 66 years with a mean age of 53. Mean duration of illness, defined as time elapsed since perceived onset of chronic systemic symptoms during or after deployment, was 22.8 years, with a range of 4 to 27 years. Most respondents reported symptom onset within a few years after the end of the conflict, while a few reported the onset within weeks of arriving in the Kuwaiti theater of operations. A little more than half the respondents considered themselves disabled due to their symptoms, while one-third reported losing the ability to work due to symptoms. Respondents described needing to reduce hours, retire early, or stop working altogether because of their symptoms.

Respondents attributed several common chronic symptoms to deployment in the Gulf Wars (Table 2). 

Most veterans surveyed were service connected for individual chronic symptoms. Some were service connected for systemic conditions such as fibromyalgia (FM), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS) (5 veterans were connected for each condition). Three of the 30 veterans had been diagnosed with GWI—2 by past VA physicians and 1 by a physician at a GWI research center in another state. Of those 3, only 1 was service connected for the condition. Three respondents were not service connected at all.

The most common VA HCPs seen were in primary care and neurology followed by psychiatry and psychology. Of non-VA HCPs, most respondents saw primary care providers (PCPs) followed by chiropractors (Table 4).

Before taking the Gulf War survey, a broad subjective question was posed. Respondents were asked whether VA HCPs were “supportive as you sought care for chronic postdeployment symptoms.” A majority of veterans reported that their VA HCPs were supportive. Reasons veterans gave for VA HCPs lack of support included feeling that HCPs did not believe them or trust their reported symptoms; did not care about their symptoms; refused to attribute their symptoms to Gulf War deployment; attributed symptoms to mental health issues; focused on doing things a certain way; or did not have the tools or information necessary to help.

Most non-VA HCPs were supportive. Reasons community HCPs were not supportive included “not looking at the whole picture,” not knowing veteran issues, not feeling comfortable with GWI, or not having much they could do.

Veterans were then asked whether they felt their HCPs were knowledgeable about GWI, and 13 respondents reported that their HCP was knowledgeable. Reasons respondents felt VA HCPs were not knowledgeable included denying that GWI exists, attributing symptoms to other conditions, not being aware of or familiar with GWI, needing education from the veteran, avoiding discussion about GWI or not caring to learn, or not knowing the latest research evidence to talk about GWI with authority. Compared with VA HCPs, veterans found community HCPs about half as likely to be knowledgeable about GWI. Many reported that community HCPs had not heard of GWI or had no knowledge about it.

Respondents also were asked what types of treatments they tried in order to typify the care received. The most common responses were pain medications, symptom-specific treatments, or “just putting up with it” (no treatment). Many patients were also self-medicating, trying lifestyle changes, or seeking alternative therapies.

Finally, respondents were asked on a scale of 0 (very unsatisfied) to 5 (very satisfied), how satisfied they were with their overall care at the VA. The majority were satisfied with their overall care, with two-thirds very satisfied (5 of 5) or pretty satisfied (4 of 5). Only 3 (10%) were unsatisfied or very unsatisfied. Respondents had the following comments about their care: “They treat me like I am important;” “I am very thankful even though they cannot figure it out;” “They are doing the best they can with no answers and not enough help;” “[I know] it is still a work in progress.” A number of respondents were satisfied with some HCPs or care for some but not all of their symptoms. Reasons respondents were less satisfied included desiring answers, feeling they were not respected, or feeling that their concerns were not addressed.

When asked for suggestions for improvement of GWI care, the most common response was providing up-to-date HCP education (Table 5).

Discussion

The veterans participating in this QI survey had similar demographics, symptomology, and exposures as did those in other studies.^1-7 Therefore, improvements based on their responses are likely applicable to the health care of veterans experiencing GWI-associated symptoms at other VA health care systems as well.

Veterans with GWI can lose significant functional capacity and productivity due to their symptoms. The symptoms are chronic and have afflicted many Gulf War veterans for nearly 3 decades. Furthermore, the prevalence of GWI in Gulf War veterans continues to increase.^5-7 These facts testify to the enormous health-related quality-of-life impact of GWI.

Veterans who meet the Kansas case definition for GWI were not diagnosed or service connected in a uniform manner. Only 3 of the 30 veterans in this study were given a unifying diagnosis that connected their chronic illness to Gulf War deployment. Under current guidelines, Gulf War veterans are able to receive compensation for chronic symptoms in 3 ways: (1) compensation for chronic unexplained symptoms existing for ≥ 6 months that appeared during active duty in the Southwest Asia theater or by December 31, 2021, and are ≥ 10% disabling; (2) the 1995 Persian Gulf War Veterans’ Act recognizes 3 multisymptom illnesses for which veterans can be service connected: FM, CFS, and functional GI disorders, including IBS; and (3) expansion to include any CMI of unknown etiology is underway. A uniform diagnostic protocol based on biomarkers and updated understanding of disease pathology would be helpful.

Respondents shared experiences that demonstrated perceived gaps in HCP support or knowledge. Overall, more respondents found their HCPs supportive. Many of the reasons respondents found HCPs unsupportive related to acknowledgment of symptoms. Also, more respondents found that both VA and non-VA HCPs lacked knowledge about GWI symptoms. These findings further highlight the need for HCP education within the VA and in community-based care.

The treatments tried by respondents also highlight potential areas for improvement. Most of the treatments were for pain; therefore, more involvement with pain clinics and specialists could be helpful. Symptom-specific medications also are appropriate, although only one-third of patients reported use. While medications are not necessarily markers of quality care, the fact that many patients self-medicate or go without treatment suggests that access to care could be improved. In 2014, the VA and the US Department of Defense (DoD) released the “VA/DoD Clinical Practice Guideline for the Management of Chronic Multisymptom Illness,” which recommended treatments for the global disease and specific symptoms.¹⁵

Since then, GWI research points to inflammatory and metabolic disease mechanisms.^11-14,16 As the underlying pathophysiology is further elucidated, practice guidelines will need to be updated to include anti-inflammatory and antioxidant treatments used in practice for GWI and similar chronic systemic illnesses (eg, CFS, FM, and IBS).^17-19

Randomized control trials are needed to determine the efficacy of such medications for the treatment of GWI. As new results emerge, disseminating and updating evidence-based guidelines in a coordinated manner will be required for veterans to receive appropriate treatment. Veterans also seek alternative or nonpharmaceutical interventions, such as physical therapy and diet changes. Improving access to integrative medicine, physical therapy, nutritionists, and other practitioners also could optimize veterans’ health and function.

HCP Education

The Gulf War veteran respondents who participated in the survey noted HCP education, research progress, and veteran inclusion as areas for improvement. Respondents requested dissemination of information on diagnosis and treatment of GWI for HCPs and updates on research and other actions. They suggested ways research could be more effective (such as subgrouping by exposure, which researchers have been doing) and could extend to veterans experiencing CMI from other conflicts as well.²⁰ Respondents also recommended team approaches or centers of excellence in order to receive more comprehensive care.

An asset of VHA is the culture of QI and education. The VA Employee Education System previously produced “Caring for Gulf War I Veterans,” a systemwide training module.²¹ In 2014, updated clinical practice guidelines for GWI were provided by the VA and the DoD, including evidence for each recommendation. In 2016, the VA in collaboration with the IOM produced a report summarizing conclusions and recommendations regarding associations between health concerns and Gulf War deployment.²² A concise guide for HCPs caring for veterans with GWI, updated in 2018, is available.²³ Updated treatment guidelines, based on evolving understanding of GWI pathophysiology, and continuing efforts to disseminate information will be essential.

Respondents most often presented to primary care, both within and outside of MVAHCS. Therefore, VA and community PCPs who see veterans should be equipped to recognize and diagnose GWI as well as be familiar with basic disease management and specialists whom they could refer their patients. Neurology was the second most common specialty seen by respondents. The most prominent symptoms of GWI are related to nervous system function in addition to evidence of underlying neuroinflammation.²⁰ Veterans may present to a neurologist with a variety of concerns, such as cognitive issues, sleep problems, migraines and headaches, and pain. Neurologists could best manage treatments targeting common neurologic GWI symptoms and neuroinflammation, especially as new treatments are discovered.

The next 2 most common specialty services seen were psychiatry and psychology (7 responses for each). Five respondents reported mental health issues as part of their chronic postdeployment symptoms. Population-based studies have indicated that rates of PTSD in Gulf War veterans is 3% to 6%, much lower than the prevalence of GWI.^8,20 The 2010 IOM study concluded that GWI symptoms cannot be ascribed to any known psychiatric disorder. Unfortunately, several surveyed veterans made it clear that they had been denied care due to HCPs attributing their symptoms solely to mental health issues. Therefore, psychiatrists and psychologists must be educated about GWI, mental health issues occurring in Gulf War veterans, and physiologic symptoms of GWI that may mimic or coincide with mental health issues. These HCPs also would be important to include in an interdisciplinary clinic for veterans with GWI.

Finally, respondents sought care from numerous other specialties, including gastroenterology, physical therapy, pulmonology, dermatology, and surgical subspecialties, such as orthopedics and otolaryngology. This wide range of specialists seen emphasizes the need for medical education, beginning in medical school. If provided education on GWI, these specialists would be able to treat veterans with GWI, know to look for updates on GWI management, or know to look for other common symptoms, such as chronic sinusitis in otolaryngology or recurring rashes in dermatology. We also recommend identifying HCPs in these specialties who could be part of an interdisciplinary clinic or be referrals for symptom management.

Protocol Implementation

HCP education and clinical care protocol implementation should be the initial focus of improving GWI management. A team of stakeholders within the different areas of MVAHCS, including education, HCPs, and administrative staff, will need to be developed. Reaching out to VA HCPs who have seen veterans with GWI will be an essential first step to equip them with updated education about the diagnosis and management of CMI. Providing integrated widespread education to current HCPs who are likely to encounter veterans with deployment-related CMI from the Gulf War, OND/OEF/OIF, or other deployments also will be necessary. Finally, educating medical trainees, including residents and medical students, will ensure continuous care for future veterans, post-9/11 veterans.

GWI presentations at medical grand rounds or at other medical community educational events could provide educational outlets. These events create face-to-face opportunities to discuss GWI/CMI education with HCPs, giving them the opportunity to offer feedback about their experiences and create relationships with other HCPs who have seen patients with GWI/CMI. At an educational event, a short postevent feedback form that indicates whether HCPs would like more information or get involved in a clinic for veterans with CMI could be included. This information would help identify key HCPs and areas within the local VA needing further improvements, such as creating a clinic for veterans with GWI.

Since 1946, the VA has worked with academic institutions to provide state-of-the-art health care to US veterans and train new HCPs to meet the health care needs of the nation. Every year, > 40,000 residents and 20,000 medical students receive medical training at VA facilities, making VA the largest single provider of medical education in the country. Therefore, providing detailed GWI/CMI education to medical students and residents as a standard part of the VA Talent Management System would be of value for all VA professionals.

GWI Clinics

Access to comprehensive care can be accomplished by organizing a clinic for veterans with GWI. The most likely effective location would be in primary care. PCPs who have seen veterans with GWI and/or expressed interest in learning more about GWI will be the initial point of contact. As the primary care service has connections to ancillary services, such as pharmacists, dieticians, psychologists, and social workers, organizing 1 day each week to see patients with GWI would improve care.

As the need for specialty care arises, the team also would need to identify specialists willing to receive referrals from HCPs of veterans with GWI. These specialists could be identified via feedback forms from educational events, surveys after an online educational training, or through relationships among VA physicians. As the clinic becomes established, it may be effective to have certain commonly seen specialists available in person, most likely neurology, psychiatry, gastroenterology, pulmonology, and dermatology. Also, relationships with a pain clinic, sleep medicine, and integrative medicine services should be established.

Measures of improvement in the veteran health care experience could include veterans’ perceptions of the supportiveness and knowledge of physicians about GWI as well as overall satisfaction. A follow-up survey on these measures of veterans involved in a GWI clinic and those not involved would be a way to determine whether these clinics better meet veterans’ needs and what additional QI is needed.

Conclusion

A significant number of Gulf War veterans experience chronic postdeployment symptoms that need to be better addressed. Physicians need to be equipped to recognize and manage GWI and similar postdeployment CMI among veterans of OEF/OIF/OND. We recommend creating an educational initiative about GWI among VA physicians and trainees, connecting physicians who see veterans with GWI, and establishing an interdisciplinary clinic with a referral system as the next steps to improve care for veterans. An additional goal would be to reach out to veteran networks to update them on GWI research, education, and available health care, as veterans are the essential stakeholders in the QI process.

Many veterans of the Gulf War are experiencing deployment-related chronic illness, known as Gulf War illness (GWI). Symptoms of GWI include cognitive impairments (mood and memory), chronic fatigue, musculoskeletal pain, gastrointestinal (GI) disorders, respiratory problems, and skin rashes.^1-4 Three survey studies of the physical and mental health of a large cohort of Gulf War and Gulf era veterans, conducted by the US Department of Veterans Affairs (VA) Office of Public Health, established the increased prevalence of GWI in the decades that followed the end of the conflict.^5-7 Thus, GWI has become the signature adverse health-related outcome of the Gulf War. Quality improvement (QI) within the Veterans Health Administration (VHA) is needed in the diagnosis and treatment of GWI.

Background

GWI was first termed chronic multisymptom illness (CMI) by the Centers for Disease Control and Prevention (CDC). According to the CDC-10 case definition, CMI in veterans of the 1990-1991 Gulf War is defined as having ≥ 1 symptoms lasting ≥ 6 months in at least 2 of 3 categories: fatigue, depressed mood and altered cognition, and musculoskeletal pain.³ The Kansas case definition of GWI is more specific and is defined as having moderate-to-severe symptoms that are unexplained by any other diagnosis, in at least 3 of 6 categories: fatigue/sleep, somatic pain, neurologic/cognition/mood, GI, respiratory, and skin.⁴ Although chronic unexplained symptoms have occurred after other modern conflicts, the prevalence of GWI among Gulf War veterans has proven higher than those of prior conflicts.⁸

The Persian Gulf War Veterans Act of 1998 and the Veterans Programs Enhancement Act of 1998 mandated studies by the Institute of Medicine (IOM) on the biologic and chemical exposures that may have contributed to illness in the Kuwaiti theater of operations.⁹ However, elucidating the etiology and underlying pathophysiology of GWI has been a major research challenge. In the absence of objective diagnostic measures, an understanding of the fundamental pathophysiology, evidence-based treatments, a single case definition, and definitive guidelines for health care providers (HCPs) for the diagnosis and management of GWI has not been produced. As a result, veterans with GWI have struggled for nearly 3 decades to find a consistent diagnosis of and an effective treatment for their condition.

According to a report by the Government Accountability Office (GAO), the VA approved only 17% of claims for compensation for veterans with GWI from 2011 to 2015, about one-third the level of approval for all other claimed disabilities.¹⁰ Although the VA applied GAO recommendations to improve the compensation process, many veterans consider that their illness is treated as psychosomatic in clinical practice, despite emerging evidence of GWI-associated biomarkers.¹¹ Others think they have been forgotten due to their short 1-year period of service in the Gulf War.¹² To realign research, guidelines, clinical care, and the health care experience of veterans with GWI, focused QI within VHA is urgently needed.

Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) are experiencing similar CMI symptoms. A study of US Army Reserve OEF/OIF veterans found that > 60% met the CDC-10 case definition for GWI 1-year postdeployment.¹³ Thus, CMI is emerging as a serious health problem for post-9/11 veterans. The evidence of postdeployment CMI among veterans of recent conflicts underscores the need to increase efforts at a national level, beginning with the VHA. This report includes a summary of Gulf War veterans’ experiences at the Minneapolis VA Health Care System (MVAHCS) and a proposal for QI of MVAHCS processes focused on HCP education and clinical care.

Methods

To determine areas of GWI health care that needed QI at the MVAHCS, veterans with GWI were contacted for a telephone survey. These veterans had participated in the Gulf War Illness Inflammation Reduction Trial (ClinicalTrials.gov. Identifier: NCT02506192). Therefore, all met the Kansas case definition for GWI.⁴ The aim of the survey was to characterize veterans’ experiences seeking health care for chronic postdeployment symptoms.

Sixty Gulf War veterans were contacted by telephone and invited to participate in a 15-minute survey about their experience seeking diagnosis and treatment for GWI. They were informed that the survey was voluntary and confidential, that it was not part of the research trial in which they had been enrolled, and that their participation would not affect compensation received from VA. Verbal consent was requested, and 30 veterans agreed to participate in the survey.

The survey included questions about the course of illness, disability and service connection status, HCPs seen, and suggestions for improvement in their care (Table 1). 

Results

Of the 30 veterans who participated in the survey, most were male with only 2 female veterans. This proportion of female veterans (7%) is similar to the overall percentage of female veterans (6.7%) of the first Gulf War.² Ages ranged from 46 to 66 years with a mean age of 53. Mean duration of illness, defined as time elapsed since perceived onset of chronic systemic symptoms during or after deployment, was 22.8 years, with a range of 4 to 27 years. Most respondents reported symptom onset within a few years after the end of the conflict, while a few reported the onset within weeks of arriving in the Kuwaiti theater of operations. A little more than half the respondents considered themselves disabled due to their symptoms, while one-third reported losing the ability to work due to symptoms. Respondents described needing to reduce hours, retire early, or stop working altogether because of their symptoms.

Respondents attributed several common chronic symptoms to deployment in the Gulf Wars (Table 2). 

Most veterans surveyed were service connected for individual chronic symptoms. Some were service connected for systemic conditions such as fibromyalgia (FM), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS) (5 veterans were connected for each condition). Three of the 30 veterans had been diagnosed with GWI—2 by past VA physicians and 1 by a physician at a GWI research center in another state. Of those 3, only 1 was service connected for the condition. Three respondents were not service connected at all.

The most common VA HCPs seen were in primary care and neurology followed by psychiatry and psychology. Of non-VA HCPs, most respondents saw primary care providers (PCPs) followed by chiropractors (Table 4).

Before taking the Gulf War survey, a broad subjective question was posed. Respondents were asked whether VA HCPs were “supportive as you sought care for chronic postdeployment symptoms.” A majority of veterans reported that their VA HCPs were supportive. Reasons veterans gave for VA HCPs lack of support included feeling that HCPs did not believe them or trust their reported symptoms; did not care about their symptoms; refused to attribute their symptoms to Gulf War deployment; attributed symptoms to mental health issues; focused on doing things a certain way; or did not have the tools or information necessary to help.

Most non-VA HCPs were supportive. Reasons community HCPs were not supportive included “not looking at the whole picture,” not knowing veteran issues, not feeling comfortable with GWI, or not having much they could do.

Veterans were then asked whether they felt their HCPs were knowledgeable about GWI, and 13 respondents reported that their HCP was knowledgeable. Reasons respondents felt VA HCPs were not knowledgeable included denying that GWI exists, attributing symptoms to other conditions, not being aware of or familiar with GWI, needing education from the veteran, avoiding discussion about GWI or not caring to learn, or not knowing the latest research evidence to talk about GWI with authority. Compared with VA HCPs, veterans found community HCPs about half as likely to be knowledgeable about GWI. Many reported that community HCPs had not heard of GWI or had no knowledge about it.

Respondents also were asked what types of treatments they tried in order to typify the care received. The most common responses were pain medications, symptom-specific treatments, or “just putting up with it” (no treatment). Many patients were also self-medicating, trying lifestyle changes, or seeking alternative therapies.

Finally, respondents were asked on a scale of 0 (very unsatisfied) to 5 (very satisfied), how satisfied they were with their overall care at the VA. The majority were satisfied with their overall care, with two-thirds very satisfied (5 of 5) or pretty satisfied (4 of 5). Only 3 (10%) were unsatisfied or very unsatisfied. Respondents had the following comments about their care: “They treat me like I am important;” “I am very thankful even though they cannot figure it out;” “They are doing the best they can with no answers and not enough help;” “[I know] it is still a work in progress.” A number of respondents were satisfied with some HCPs or care for some but not all of their symptoms. Reasons respondents were less satisfied included desiring answers, feeling they were not respected, or feeling that their concerns were not addressed.

When asked for suggestions for improvement of GWI care, the most common response was providing up-to-date HCP education (Table 5).

Discussion

The veterans participating in this QI survey had similar demographics, symptomology, and exposures as did those in other studies.^1-7 Therefore, improvements based on their responses are likely applicable to the health care of veterans experiencing GWI-associated symptoms at other VA health care systems as well.

Veterans with GWI can lose significant functional capacity and productivity due to their symptoms. The symptoms are chronic and have afflicted many Gulf War veterans for nearly 3 decades. Furthermore, the prevalence of GWI in Gulf War veterans continues to increase.^5-7 These facts testify to the enormous health-related quality-of-life impact of GWI.

Veterans who meet the Kansas case definition for GWI were not diagnosed or service connected in a uniform manner. Only 3 of the 30 veterans in this study were given a unifying diagnosis that connected their chronic illness to Gulf War deployment. Under current guidelines, Gulf War veterans are able to receive compensation for chronic symptoms in 3 ways: (1) compensation for chronic unexplained symptoms existing for ≥ 6 months that appeared during active duty in the Southwest Asia theater or by December 31, 2021, and are ≥ 10% disabling; (2) the 1995 Persian Gulf War Veterans’ Act recognizes 3 multisymptom illnesses for which veterans can be service connected: FM, CFS, and functional GI disorders, including IBS; and (3) expansion to include any CMI of unknown etiology is underway. A uniform diagnostic protocol based on biomarkers and updated understanding of disease pathology would be helpful.

Respondents shared experiences that demonstrated perceived gaps in HCP support or knowledge. Overall, more respondents found their HCPs supportive. Many of the reasons respondents found HCPs unsupportive related to acknowledgment of symptoms. Also, more respondents found that both VA and non-VA HCPs lacked knowledge about GWI symptoms. These findings further highlight the need for HCP education within the VA and in community-based care.

The treatments tried by respondents also highlight potential areas for improvement. Most of the treatments were for pain; therefore, more involvement with pain clinics and specialists could be helpful. Symptom-specific medications also are appropriate, although only one-third of patients reported use. While medications are not necessarily markers of quality care, the fact that many patients self-medicate or go without treatment suggests that access to care could be improved. In 2014, the VA and the US Department of Defense (DoD) released the “VA/DoD Clinical Practice Guideline for the Management of Chronic Multisymptom Illness,” which recommended treatments for the global disease and specific symptoms.¹⁵

Since then, GWI research points to inflammatory and metabolic disease mechanisms.^11-14,16 As the underlying pathophysiology is further elucidated, practice guidelines will need to be updated to include anti-inflammatory and antioxidant treatments used in practice for GWI and similar chronic systemic illnesses (eg, CFS, FM, and IBS).^17-19

Randomized control trials are needed to determine the efficacy of such medications for the treatment of GWI. As new results emerge, disseminating and updating evidence-based guidelines in a coordinated manner will be required for veterans to receive appropriate treatment. Veterans also seek alternative or nonpharmaceutical interventions, such as physical therapy and diet changes. Improving access to integrative medicine, physical therapy, nutritionists, and other practitioners also could optimize veterans’ health and function.

HCP Education

The Gulf War veteran respondents who participated in the survey noted HCP education, research progress, and veteran inclusion as areas for improvement. Respondents requested dissemination of information on diagnosis and treatment of GWI for HCPs and updates on research and other actions. They suggested ways research could be more effective (such as subgrouping by exposure, which researchers have been doing) and could extend to veterans experiencing CMI from other conflicts as well.²⁰ Respondents also recommended team approaches or centers of excellence in order to receive more comprehensive care.

An asset of VHA is the culture of QI and education. The VA Employee Education System previously produced “Caring for Gulf War I Veterans,” a systemwide training module.²¹ In 2014, updated clinical practice guidelines for GWI were provided by the VA and the DoD, including evidence for each recommendation. In 2016, the VA in collaboration with the IOM produced a report summarizing conclusions and recommendations regarding associations between health concerns and Gulf War deployment.²² A concise guide for HCPs caring for veterans with GWI, updated in 2018, is available.²³ Updated treatment guidelines, based on evolving understanding of GWI pathophysiology, and continuing efforts to disseminate information will be essential.

Respondents most often presented to primary care, both within and outside of MVAHCS. Therefore, VA and community PCPs who see veterans should be equipped to recognize and diagnose GWI as well as be familiar with basic disease management and specialists whom they could refer their patients. Neurology was the second most common specialty seen by respondents. The most prominent symptoms of GWI are related to nervous system function in addition to evidence of underlying neuroinflammation.²⁰ Veterans may present to a neurologist with a variety of concerns, such as cognitive issues, sleep problems, migraines and headaches, and pain. Neurologists could best manage treatments targeting common neurologic GWI symptoms and neuroinflammation, especially as new treatments are discovered.

The next 2 most common specialty services seen were psychiatry and psychology (7 responses for each). Five respondents reported mental health issues as part of their chronic postdeployment symptoms. Population-based studies have indicated that rates of PTSD in Gulf War veterans is 3% to 6%, much lower than the prevalence of GWI.^8,20 The 2010 IOM study concluded that GWI symptoms cannot be ascribed to any known psychiatric disorder. Unfortunately, several surveyed veterans made it clear that they had been denied care due to HCPs attributing their symptoms solely to mental health issues. Therefore, psychiatrists and psychologists must be educated about GWI, mental health issues occurring in Gulf War veterans, and physiologic symptoms of GWI that may mimic or coincide with mental health issues. These HCPs also would be important to include in an interdisciplinary clinic for veterans with GWI.

Finally, respondents sought care from numerous other specialties, including gastroenterology, physical therapy, pulmonology, dermatology, and surgical subspecialties, such as orthopedics and otolaryngology. This wide range of specialists seen emphasizes the need for medical education, beginning in medical school. If provided education on GWI, these specialists would be able to treat veterans with GWI, know to look for updates on GWI management, or know to look for other common symptoms, such as chronic sinusitis in otolaryngology or recurring rashes in dermatology. We also recommend identifying HCPs in these specialties who could be part of an interdisciplinary clinic or be referrals for symptom management.

Protocol Implementation

HCP education and clinical care protocol implementation should be the initial focus of improving GWI management. A team of stakeholders within the different areas of MVAHCS, including education, HCPs, and administrative staff, will need to be developed. Reaching out to VA HCPs who have seen veterans with GWI will be an essential first step to equip them with updated education about the diagnosis and management of CMI. Providing integrated widespread education to current HCPs who are likely to encounter veterans with deployment-related CMI from the Gulf War, OND/OEF/OIF, or other deployments also will be necessary. Finally, educating medical trainees, including residents and medical students, will ensure continuous care for future veterans, post-9/11 veterans.

GWI presentations at medical grand rounds or at other medical community educational events could provide educational outlets. These events create face-to-face opportunities to discuss GWI/CMI education with HCPs, giving them the opportunity to offer feedback about their experiences and create relationships with other HCPs who have seen patients with GWI/CMI. At an educational event, a short postevent feedback form that indicates whether HCPs would like more information or get involved in a clinic for veterans with CMI could be included. This information would help identify key HCPs and areas within the local VA needing further improvements, such as creating a clinic for veterans with GWI.

Since 1946, the VA has worked with academic institutions to provide state-of-the-art health care to US veterans and train new HCPs to meet the health care needs of the nation. Every year, > 40,000 residents and 20,000 medical students receive medical training at VA facilities, making VA the largest single provider of medical education in the country. Therefore, providing detailed GWI/CMI education to medical students and residents as a standard part of the VA Talent Management System would be of value for all VA professionals.

GWI Clinics

Access to comprehensive care can be accomplished by organizing a clinic for veterans with GWI. The most likely effective location would be in primary care. PCPs who have seen veterans with GWI and/or expressed interest in learning more about GWI will be the initial point of contact. As the primary care service has connections to ancillary services, such as pharmacists, dieticians, psychologists, and social workers, organizing 1 day each week to see patients with GWI would improve care.

As the need for specialty care arises, the team also would need to identify specialists willing to receive referrals from HCPs of veterans with GWI. These specialists could be identified via feedback forms from educational events, surveys after an online educational training, or through relationships among VA physicians. As the clinic becomes established, it may be effective to have certain commonly seen specialists available in person, most likely neurology, psychiatry, gastroenterology, pulmonology, and dermatology. Also, relationships with a pain clinic, sleep medicine, and integrative medicine services should be established.

Measures of improvement in the veteran health care experience could include veterans’ perceptions of the supportiveness and knowledge of physicians about GWI as well as overall satisfaction. A follow-up survey on these measures of veterans involved in a GWI clinic and those not involved would be a way to determine whether these clinics better meet veterans’ needs and what additional QI is needed.

Conclusion

A significant number of Gulf War veterans experience chronic postdeployment symptoms that need to be better addressed. Physicians need to be equipped to recognize and manage GWI and similar postdeployment CMI among veterans of OEF/OIF/OND. We recommend creating an educational initiative about GWI among VA physicians and trainees, connecting physicians who see veterans with GWI, and establishing an interdisciplinary clinic with a referral system as the next steps to improve care for veterans. An additional goal would be to reach out to veteran networks to update them on GWI research, education, and available health care, as veterans are the essential stakeholders in the QI process.

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

[email protected]

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

[email protected]

MILWAUKEE – Individuals with chronic pain frequently have disrupted sleep and also may be at risk for opioid use disorder. However, even with advanced monitoring, it’s not clear how sleep modulates pain and opioid cravings.

Sleep has an impact on positive and negative affect, but new research shows that the link between sleep and mood states that may contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain Society, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD).

Affective function, mesolimbic system function, and pain modulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models.

Finally, two “proximal indicators” of relapse risk, affect and heroin craving, might be affected by both sleep and pain, and Dr. Finan and collaborators sought to explore that association.

The work was part of a larger study looking at the natural history of OUD and OUD with comorbid chronic pain. To participate in this parent study, adults with OUD had to be seeking treatment or currently enrolled in methadone or buprenorphine maintenance treatment, and without current major depressive disorder. Also, patients could not have a history of significant mental illness, cognitive impairment, or a medical condition that would interfere with study participation. A total of 56 patients participated, and 20 of these individuals also had chronic pain.

Those with OUD and chronic pain qualified if they had pain (not related to opioid withdrawal) averaging above 3 on a 0-10 pain rating scale over the past week; additional criteria included pain for at least the past 3 months, with 10 or more days per month of pain.

Pain ratings were captured via a smartphone app that prompted participants to enter a pain rating at three random times during each day. Each evening, patients also completed a sleep diary giving information about bedtime, sleep onset latency, waking after sleep onset, and wake time for the preceding day.

A self-applied ambulatory electroencephalogram applied to the forehead was used for up to 7 consecutive nights to capture sleep continuity estimates; the device has been validated against polysomnography data in other work. Participants were given incentives to use the device, and this “yielded strong adherence,” with an average of 5 nights of use per participant, Dr. Finan said.

Patients were an average age of about 49 years, and were 75% male. African American participants made up just over half of the cohort, and 43% were white. Participants were roughly evenly divided in the type of maintenance therapy they were taking. Overall, 39% of participants had a positive urine toxicology screen.

For patients with chronic pain, 45% of all momentary pain reports had a pain score over zero, with a mean of 32 days of pain. Looking at the data another way, 58% of all patient-days had at least one momentary report of pain greater than zero, said Dr. Finan. On average, participants recorded a pain score of 2.27.

Brief Pain Inventory scores at baseline showed a mean severity of 5, and a pain interference score of 5.07.

Participants with OUD and chronic pain did not differ across any EEG-recorded sleep measures, compared with those with OUD alone. However, subjective reports of sleep were actually better overall for those with chronic pain than the objective EEG reports. The EEG recordings captured an average of 9.11 minutes more of waking after sleep onset (P less than .001). Also, total sleep time was 10.37 minutes shorter as recorded by the EEG than by self-report (P less than .001). Overall sleep efficiency was also worse by 5.96 minutes according to the EEG, compared with self-report (P less than .001).

“Sleep is objectively poor but subjectively ‘normal’ and variable in opioid use disorder patients,” Dr. Finan said. In aggregate, however, neither diary-based subjective nor EEG-based objective sleep measures differed between those with and without chronic pain in the research cohort. This phenomenon of sleep efficiency being self-reported as higher than objective measures capture sleep has also been seen in those newly abstinent from cocaine, Dr. Finan said, adding that it’s possible individuals with substance use disorder who are new to treatment simply feel better than they have in some time along many dimensions, with sleep being one such domain.

Pain on a given day didn’t predict poor sleep on that night, except that sleep onset took slightly longer (P = .01), said Dr. Finan. He noted that “there was no substantive effect on other sleep continuity parameters.”

Looking at how negative affect mediated craving for heroin, Dr. Finan and colleagues found that negative affect–related craving was significantly greater for those with chronic pain (P less than .001). Unlike findings in patients without OUD, having disrupted sleep continuity was more associated with increased daily negative affect, rather than decreased positive affect. And this increased negative affect was associated with heroin cravings, said Dr. Finan. “In the past few years, we’ve seen quite a few studies that have found some abnormalities in the reward system in patients with chronic pain.” Whether poor sleep is a mediator of these abnormalities deserves further study.

The study was supported by the National Institutes of Health. Dr. Finan reported no outside sources of funding.

[email protected]