A computer-based, self-administered test for cognitive impairment could be used to screen for cognitive impairment in adults with systemic lupus erythematosus, new research suggests.

In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).

First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.

“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”

The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.

A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).

The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.

“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.

The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.

The composite index performed similarly well among patients with or without neuropsychiatric lupus.

“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.

The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”

The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.

SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.

A computer-based, self-administered test for cognitive impairment could be used to screen for cognitive impairment in adults with systemic lupus erythematosus, new research suggests.

In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).

First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.

“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”

The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.

A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).

The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.

“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.

The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.

The composite index performed similarly well among patients with or without neuropsychiatric lupus.

“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.

The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”

The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.

SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.

A computer-based, self-administered test for cognitive impairment could be used to screen for cognitive impairment in adults with systemic lupus erythematosus, new research suggests.

In a paper published in Arthritis Care & Research, researchers assessed the validity of the Automated Neuropsychological Assessment Metrics (ANAM) test in 211 adult patients with systemic lupus erythematosus (SLE).

First author Oshrat E. Tayer-Shifman, MD, of the University of Toronto Lupus Clinic and coauthors wrote that current assessment of cognitive impairment in adults with SLE is done using the American College of Rheumatology neuropsychological battery (ACR-NB). However, this approach involves protected tests that require specialized personnel and takes around 1 hour to administer, as well as time for scoring and interpretation.

“For many clinics, these are notable barriers to accessing CI [cognitive impairment] assessment, as health care payers do not cover these costs,” the investigators wrote. And although briefer cognitive screening tools, such as the Montreal Cognitive Assessment, the Controlled Oral Word Association Test, and the Hopkins Verbal Learning Test–Revised, have been examined in studies of patients with SLE, “they also require specialized personnel for administration and interpretation and cannot be self-administered. In addition, their validity for the screening for CI in SLE has not been well established. Thus, there is an unmet need for a screening assessment for CI that is validated for SLE and that can be applied in an ambulatory clinic setting without specialized personnel.”

The full ANAM battery requires about 40 minutes and has been used to screen cognitive performance in a range of clinical contexts.

A total of 96 patients (46%) had CI and 52 (25%) did not, according to the ACR-NB, while the results were indeterminate in the remaining 63 (30%).

The study showed that patients without CI performed significantly better on the majority of the ANAM subtests in comparison with patients who have cognitive impairment. This was particularly evident on mean reaction time and the number of correct responses per minute (a measure of cognitive efficiency), but less so for percentage of correct responses and consistency of response speed.

“Three of the most affected cognitive domains in the CI patients in this cohort, as well as in previous studies, were learning and memory, visual spatial construction, and simple attention and speed of processing,” the researchers wrote.

The investigators created testing models using the subtests that were most discriminative for CI. The two best models included one encompassing the percentage of correct responses, consistency of response speed, and mean reaction time, as well as one encompassing these three factors as well as the number of correct responses per minute. The investigators then derived candidate ANAM composite indices from these two models. For one composite index that used 8 of the 15 ANAM subtests and included five of the six cognitive domains tested on the ACR-NB, a high and a low cutoff value gave an area under the curve of 79%, sensitivity of 80%-89%, specificity of 54%-70%, positive predictive value of 78%-83%, and negative predictive value of 65%-74%.

The composite index performed similarly well among patients with or without neuropsychiatric lupus.

“This approach not only enables us to use a cost-effective screening approach without specialized personnel, but we have reduced the duration of the ANAM battery itself. The ANAM [version 4 General Neuropsychological Screening] full battery requires approximately 40 minutes to administer, while our analyses enable us to limit the number of ANAM subtests used, shortening the testing duration to 20 minutes,” they wrote.

The investigators noted that the study included only individuals with sufficient English language ability to complete the tests, and they also excluded patients with indeterminate cognitive status. “We reasoned that they represented a nonhomogeneous group, and without a clear consensus on the definition of CI in SLE patients, we chose to concentrate on the more clearly defined CI SLE patients.”

The study was supported by grants from the Arthritis Society of Canada, Physician’s Services, the Kathi and Peter Kaiser Family, and the Lou and Marissa Rocca Family. One author was supported by the Arthritis Society and the Canadian Rheumatology Association. No conflicts of interest were declared.

SOURCE: Tayer-Shifman OE et al. Arthritis Care Res. 2019 Oct 18. doi: 10.1002/acr.24096.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.^1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.² The etiology remains unclear.² Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.^2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.³

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.^2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.⁵ But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.⁵

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.^7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).^2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.⁴ IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.^2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.⁹ Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.^2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).^9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.¹² A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.¹³ Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.¹⁴ However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.¹⁵

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.¹⁴ Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.⁷

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.¹⁶ The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.¹⁶

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.¹⁷ However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.¹⁸ In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.⁸

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.¹⁹ In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.^20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.^1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.² The etiology remains unclear.² Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.^2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.³

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.^2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.⁵ But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.⁵

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.^7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).^2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.⁴ IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.^2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.⁹ Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.^2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).^9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.¹² A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.¹³ Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.¹⁴ However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.¹⁵

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.¹⁴ Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.⁷

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.¹⁶ The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.¹⁶

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.¹⁷ However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.¹⁸ In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.⁸

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.¹⁹ In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.^20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

Adiposis dolorosa (AD), or Dercum disease, is a rare disorder that was first described in 1888 and characterized by the National Organization of Rare Disorders (NORD) as a chronic pain condition of the adipose tissue generally found in patients who are overweight or obese.^1,2 AD is more common in females aged 35 to 50 years and proposed to be a disease of postmenopausal women, though no prevalence studies exist.² The etiology remains unclear.² Several theories have been proposed, including endocrine and nervous system dysfunction, adipose tissue dysregulation, or pressure on peripheral nerves and chronic inflammation.^2-4 Genetic, autoimmune, and trauma also have been proposed as a mechanism for developing the disease. Treatment modalities focusing on narcotic analgesics have been ineffective in long-term management.³

The objective of the case presentation is to report a variety of approaches for AD and their relative successes at pain control in order to assist other medical professionals who may come across patients with this rare condition.

Case Presentation

A 53-year-old male with a history of blast exposure-related traumatic brain injury, subsequent stroke with residual left hemiparesis, and seizure disorder presented with a 10-year history of nodule formation in his lower extremities causing restriction of motion and pain. The patient had previously undergone lower extremity fasciotomies for compartment syndrome with minimal pain relief. In addition, nodules over his abdomen and chest wall had been increasing over the past 5 years. He also experienced worsening fatigue, cramping, tightness, and paresthesias of the affected areas during this time. Erythema and temperature allodynia were noted in addition to an 80-pound weight gain. From the above symptoms and nodule excision showing histologic signs of lipomatous growth, a diagnosis of AD was made.

The following constitutes the approximate timetable of his treatments for 9 years. He was first diagnosed incidentally at the beginning of this period with AD during an electrodiagnostic examination. He had noticed the lipomas when he was in his 30s, but initially they were not painful. He was referred for treatment of pain to the physical medicine and rehabilitation department.

For the next 3 years, he was treated with prolotherapy. Five percent dextrose in water was injected around many of the painful lipomas in the upper extremities. He noted after the second round of neural prolotherapy that he had reduced swelling of his upper extremities and the lipomas decreased in size. He experienced mild improvement in pain and functional usage of his arms.

He continued to receive neural prolotherapy into the nodules in the arms, legs, abdomen, and chest wall. The number of painful nodules continued to increase, and the patient was started on hydrocodone 10 mg/acetaminophen 325 mg (1 tablet every 6 hours as needed) and methadone for pain relief. He was initially started on 5 mg per day of methadone and then was increased in a stepwise, gradual fashion to 10 mg in the morning and 15 mg in the evening. He transitioned to morphine sulfate, which was increased to a maximum dose of 45 mg twice daily. This medication was slowly tapered due to adverse effects (AEs), including sedation.

After weaning off morphine sulfate, the patient was started on lidocaine infusions every 3 months. Each infusion provided at least 50% pain reduction for 6 to 8 weeks. He was approved by the US Department of Veterans Affairs (VA) to have Vaser (Bausch Health, Laval, Canada) minimally invasive ultrasound liposuction treatment, performed at an outside facility. The patient was satisfied with the pain relief that he received and noted that the number of lipomas greatly diminished. However, due to funding issues, this treatment was discontinued after several months.

The patient had moderately good pain relief with methadone 5 mg in the morning, and 15 mg in the evening. However, the patient reported significant somnolence during the daytime with the regimen. Attempts to wean the patient off methadone was met with uncontrollable daytime pain. With suboptimal oral pain regimen, difficulty obtaining Vaser treatments, and limitation in frequency of neural prolotherapy, the decision was made to initiate 12 treatments of Calmare (Fairfield, CT) cutaneous electrostimulation.

During his first treatment, he had the electrodes placed on his lower extremities. The pre- and posttreatment 10-point visual analog scale (VAS) scores were 9 and 0, respectively, after the first visit. The position of the electrodes varied, depending on the location of his pain, including upper extremities and abdominal wall. During the treatment course, the patient experienced an improvement in subjective functional status. He was able to sleep in the same bed as his wife, shake hands without severe pain, and walk .25 mile, all of which he was unable to do before the electrostimulative treatment. He also reported overall improvement in emotional well-being, resumption of his hobbies (eg, playing the guitar), and social engagement. Methadone was successfully weaned off during this trial without breakthrough pain. This improvement in pain and functional status continued for several weeks; however, he had an exacerbation of his pain following a long plane flight. Due to uncertain reliability of pain relief with the procedure, the pain management service initiated a regimen of methadone 10 mg twice daily to be initiated when a procedure does not provide the desired duration of pain relief and gradually discontinued following the next interventional procedure.

The patient continued a regimen that included lidocaine infusions, neural prolotherapy, Calmare electrostimulative therapy, as well as lymphedema massage. Additionally, he began receiving weekly acupuncture treatments. He started with traditional full body acupuncture and then transitioned to battlefield acupuncture (BFA). Each acupuncture treatment provided about 50% improvement in pain on the VAS, and improved sleep for 3 days posttreatment.

However, after 18 months of the above treatment protocol, the patient experienced a general tonic-clonic seizure at home. Due to concern for the lowered seizure threshold, lidocaine infusions and methadone were discontinued. Long-acting oral morphine was initiated. The patient continued Calmare treatments and neural prolotherapy after a seizure-free interval. This regimen provided the patient with temporary pain relief but for a shorter duration than prior interventions.

Ketamine infusions were eventually initiated about 5 years after the diagnosis of AD was made, with postprocedure pain as 0/10 on the VAS. Pain relief was sustained for 3 months, with the notable AEs of hallucinations in the immediate postinfusion period. Administration consisted of the following: 500 mg of ketamine in a 500 mL bag of 0.9% NaCl. A 60-mg slow IV push was given followed by 60 mg/h increased every 15 min by 10 mg/h for a maximum dose of 150 mg/h. In a single visit the maximum total dose of ketamine administered was 500 mg. The protocol, which usually delivered 200 mg in a visit but was increased to 500 mg because the 200-mg dose was ineffective, was based on protocols at other institutions to accommodate the level of monitoring available in the Interventional Pain Clinic. The clinic also developed an infusion protocol with at least 1 month between treatments. The patient continues to undergo scheduled ketamine infusions every 14 weeks in addition to monthly BFA. The patient reported near total pain relief for about a month following ketamine infusion, with about 3 months of sustained pain relief. Each BFA session continues to provide 3 days of relief from insomnia. Calmare treatments and the neural prolotherapy regimen continue to provide effective but temporary relief from pain.

Discussion

Currently there is no curative treatment for AD. The majority of the literature is composed of case reports without summaries of potential interventions and their efficacies. AD therapies focus on symptom relief and mainly include pharmacologic and surgical intervention. In this case report several novel treatment modalities have been shown to be partially effective.

Surgical Intervention

Liposuction and lipoma resection have been described as effective only in the short term for AD.^2,4-6 Hansson and colleagues suggested liposuction avulsion for sensory nerves and a portion of the proposed abnormal nerve connections between the peripheral nervous system and sensory nerves as a potential therapy for pain improvement.⁵ But the clinical significance of pain relief from liposuction is unclear and is contraindicated in recurrent lipomas.⁵

Pharmaceutical Approach

Although relief with nonsteroidal anti-inflammatory drugs and narcotic analgesics have been unpredictable, Herbst and Asare-Bediako described significant pain relief in a subset of patients with AD with a variety of oral analgesics.^7,8 However, the duration of this relief was not clearly stated, and the types or medications or combinations were not discussed. Other pharmacologic agents trialed in the treatment of AD include methotrexate, infliximab, Interferon α-2b, and calcium channel modulators (pregabalin and oxcarbazepine).^2,9-11 However, the mechanism and significance of pain relief from these medications remain unclear.

Subanesthesia Therapy

Lidocaine has been used as both a topical agent and an IV infusion in the treatment of chronic pain due to AD for decades. Desai and colleagues described 60% sustained pain reduction in a patient using lidocaine 5% transdermal patches.⁴ IV infusion of lidocaine has been described in various dosages, though the mechanism of pain relief is ambiguous, and the duration of effect is longer than the biologic half-life.^2-4,9 Kosseifi and colleagues describe a patient treated with local injections of lidocaine 1% and obtained symptomatic relief for 3 weeks.⁹ Animal studies suggest the action of lidocaine involves the sodium channels in peripheral nerves, while another study suggested there may be an increase in sympathetic nervous system activity after the infusion of lidocaine.^2,9

Ketamine infusions not previously described in the treatment of AD have long been used to treat other chronic pain syndromes (chronic cancer pain, complex regional pain syndrome [CRPS], fibromyalgia, migraine, ischemic pain, and neuropathic pain).^9,12,13 Ketamine has been shown to decrease pain intensity and reduce the amount of opioid analgesic necessary to achieve pain relief, likely through the antagonism of N-methyl-D-aspartate receptors.¹² A retrospective review by Patil and Anitescu described subanesthetic ketamine infusions used as a last-line therapy in refractory pain syndromes. They found ketamine reduced VAS scores from mean 8.5 prior to infusion to 0.8 after infusion in patients with CRPS and from 7.0 prior to infusion to 1.0 in patient with non-CRPS refractory pain syndromes.¹³ Hypertension and sedation were the most frequent AEs of ketamine infusion, though a higher incidence of hallucination and confusion were noted in non-CRPS patients. Hocking and Cousins suggest that psychotomimetic AEs of ketamine infusion may be more likely in patients with anxiety.¹⁴ However, it is important to note that ketamine infusion studies have been heterogeneous in their protocol, and only recently have standardization guidelines been proposed.¹⁵

Physical Modalities

Manual lymphatic massage has been described in multiple reports for symptom relief in patients with cancer with malignant growth causing outflow lymphatic obstruction. This technique also has been used to treat the obstructive symptoms seen with the lipomatous growths of AD. Lange and colleagues described a case as providing reduction in pain and the diameter of extremities with twice weekly massage.¹⁴ Herbst and colleagues noted that patients had an equivocal response to massage, with some patients finding that it worsened the progression of lipomatous growths.⁷

Electrocutaneous Stimulation

In a case study by Martinenghi and colleagues, a patient with AD improved following transcutaneous frequency rhythmic electrical modulation system (FREMS) treatment.¹⁶ The treatment involved 4 cycles of 30 minutes each for 6 months. The patient had an improvement of pain on the VAS from 6.4 to 1.7 and an increase from 12 to 18 on the 100-point Barthel index scale for performance in activities of daily living, suggesting an improvement of functional independence as well.¹⁶

The MC5-A Calmare is another cutaneous electrostimulation modality that previously has been used for chronic cancer pain management. This FDA-cleared device is indicated for the treatment of various chronic pain syndromes. The device is proposed to stimulate 5 separate pain areas via cutaneous electrodes applied beyond and above the painful areas in order to “scramble” pain information and reduce perception of chronic pain intensity. Ricci and colleagues included cancer and noncancer subjects in their study and observed reduction in pain intensity by 74% (on numeric rating scale) in the entire subject group after 10 days of treatments. Further, no AEs were reported in either group, and most of the subjects were willing to continue treatment.¹⁷ However, this modality was limited by concerns with insurance coverage, access to a Calmare machine, operator training, and reproducibility of electrode placement to achieve “zero pain” as is the determinant of device treatment cycle output by the manufacturer.

Perineural Injection/Prolotherapy

Perineural injection therapy (PIT) involves the injection of dextrose solution into tissues surrounding an inflamed nerve to reduce neuropathic inflammation. The proposed source of this inflammation is the stimulation of the superficial branches of peptidergic peripheral nerves. Injections are SC and target the affected superficial nerve pathway. Pain relief is usually immediate but requires several treatments to ensure a lasting benefit. There have been no research studies or case reports on the use of PIT or prolotherapy and AD. Although there is a paucity of published literature on the efficacy of PIT, it remains an alternative modality for treatment of chronic pain syndromes. In a systematic review of prolotherapy for chronic musculoskeletal pain, Hauser and colleagues supported the use of dextrose prolotherapy to treat chronic tendinopathies, osteoarthritis of finger and knee joints, spinal and pelvic pain if conservative measures had failed. However, the efficacy on acute musculoskeletal pain was uncertain.¹⁸ In addition to the paucity of published literature, prolotherapy is not available to many patients due to lack of insurance coverage or lack of providers able to perform the procedure.

Hypobaric Pressure Therapy

Hypobaric pressure therapy has been offered as an alternative “touch-free” method for treatment of pain associated with edema. Herbst and Rutledge describe a pilot study focusing on hypobaric pressure therapy in patients with AD using a cyclic altitude conditioning system, which significantly decreased the Pain Catastrophizing Scale (tendency to catastrophize pain symptoms) in patients with AD after 5 days of therapy. VAS scores also demonstrated a linear decrease over 5 days.⁸

Acupuncture

There have been no research studies or case reports regarding the use of either traditional full body acupuncture or BFA in management of AD. However, prior studies have been performed that suggest that acupuncture can be beneficial in chronic pain relief. For examples, a Cochrane review by Manheimer and colleagues showed that acupuncture had a significant benefit in pain relief in subjects with peripheral joint arthritis.¹⁹ In another Cochrane review there was low-to-moderate level evidence compared with no treatment in pain relief, but moderate-level evidence that the effect of acupuncture does not differ from sham (placebo) acupuncture.^20,21

Conclusion

Current therapeutic approaches to AD focus on invasive surgical intervention, chronic opiate and oral medication management. However, we have detailed several additional approaches to AD treatment. Ketamine infusions, which have long been a treatment in other chronic pain syndromes may present a viable alternative to lidocaine infusions in patients with AD. Electrocutaneous stimulation is a validated treatment of chronic pain syndromes, including chronic neuropathic pain and offers an alternative to surgical or pharmacologic management. Further, PIT offers another approach to neuropathic pain management, which has yet to be fully explored. As no standard treatment approach exists for patients with AD, multimodal therapies should be considered to optimize pain management and reduce dependency on opiate mediations.

Acknowledgments
Hunter Holmes McGuire Research Institute and the Physical Medicine and Rehabilitation Department provided the resources and facilities to make this work possible.

Osteoporosis is a disease characterized by the loss of bone density.¹ Bone is normally porous and is in a state of flux due to changes in regeneration caused by osteoclast or osteoblast activity. However, age and other factors can accelerate loss in bone density and lead to decreased bone strength and an increased risk of fracture. In men, bone mineral density (BMD) can begin to decline as early as age 30 to 40 years. By age 80 years, 25% of total bone mass may be lost.²

Of the 44 million Americans with low BMD or osteoporosis, 20% are men.¹ This group accounts for up to 40% of all osteoporotic fractures. About 1 in 4 men aged ≥ 50 years may experience a lifetime fracture. Fractures may lead to chronic pain, disability, increased dependence, and potentially death. These complications cause expenditures upward of $4.1 billion annually in North America alone.^3,4 About 80,000 US men will experience a hip fracture each year, one-third of whom will die within that year. This constitutes a mortality rate 2 to 3 times higher than that of women. Osteoporosis often goes undiagnosed and untreated due to a lack of symptoms until a fracture occurs, underlining the potential benefit of preemptive screening.

In 2007, Shekell and colleagues outlined how the US Department of Veterans Affairs (VA) screened men for osteoporosis.⁵ At the time, 95% of the VA population was male, though it has since dropped to 91%.⁶ Shekell and colleagues estimated that about 200,0000 to 400,0000 male veterans had osteoporosis.⁵ Osteoporotic risk factors deemed specific to veterans were excessive alcohol use, spinal cord injury and lack of weight-bearing exercise, prolonged corticosteroid use, and androgen deprivation therapy in prostate cancer. Different screening techniques were assessed, and the VA recommended the Osteoporosis Self-Assessment Tool (OST).⁵ Many organizations have developed clinical guidance, including who should be screened; however, screening for men remains a controversial area due to a lack of any strong recommendations (Table 1).

Endocrine Society screening guidelines for men are the most specific: testing BMD in men aged ≥ 70 years, or if aged 50 to 69 years with an additional risk factor (eg, low body weight, smoking, chronic obstructive pulmonary disease, chronic steroid use).¹ The Fracture Risk Assessment tool (FRAX) score is often cited as a common screening tool. It is a free online questionnaire that provides a 10-year probability risk of hip or major osteoporotic fracture.¹¹ However, this tool is limited by age, weight, and the assumption that all questions are answered accurately. Some of the information required includes the presence of a number of risk factors, such as alcohol use, glucocorticoids, and medical history of rheumatoid arthritis, among others (Table 2). The OST score, on the other hand, is a calculation that does not take into account other risk factors (Figure 1). This tool categorizes the patient into low, moderate, or high risk for osteoporosis.⁸

In a study of 4,000 men aged ≥ 70 years, Diem and colleagues found that OST performed better than FRAX in identifying men who were osteoporotic as well as reducing the proportion of men referred for dual-energy X-ray absorptiometry (DEXA) scan vs universal screening.¹² The mean study participant was aged 76 years, overweight, and had a history of smoking; the majority were white. An OST score of < 2 captured 64% of the total population, 82% of whom had a T-score of < 2.5, which is a diagnostic for osteoporosis. A FRAX score of 9.3% captured 42% of the total population, but only 59% of patients with a T-score of < 2.5.

A 2017 VA Office of Rural Health study examined the utility of OST to screen referred patients aged > 50 years to receive DEXA scans in patient aligned care team (PACT) clinics at 3 different VA locations.¹³ The study excluded patients who had been screened previously or treated for osteoporosis, were receiving hospice care; 1 site excluded patients aged > 88 years. Two of the sites also reviewed the patient’s medications to screen for agents that may contribute to increased fracture risk. Veterans identified as high risk were referred for education and offered a DEXA scan and treatment. In total, 867 veterans were screened; 19% (168) were deemed high risk, and 6% (53) underwent DEXA scans. The study noted that only 15 patients had reportable DEXA scans and 10 were positive for bone disease.

As there has been documented success in the PACT setting in implementing standardized protocols for screening and treating veterans, it is reasonable to extend the concept into other VA services. The home-based primary care (HBPC) population is especially vulnerable due to the age of patients, limited weight-bearing exercise to improve bone strength, and limited access to DEXA scans due to difficulty traveling outside of the home. Despite these issues, a goal of the HBPC service is to provide continual care for veterans and improve their health so they may return to the community setting. As a result, patients are followed frequently, providing many opportunities for interventions. This study aims to determine the proportion of HBPC patients who are at high risk for osteoporosis and can receive a DEXA scan for evaluation.

Methods

This study was a retrospective chart analysis using descriptive statistics. It was reviewed and approved by the institutional review board at Captain James A. Lovell Federal Health Care Center (FHCC). Patients were included in the study if they were enrolled in the HBPC program at FHCC. Patients were excluded if they were receiving hospice or palliative care, had a limited life expectancy per the HBPC provider, or had a diagnosis of osteoporosis that was being managed by a VA endocrinologist, rheumatologist, or non-VA provider.

The study was conducted from February 1, 2018, through November 30, 2018. All chart reviews were done through the FHCC electronic health record. A minimum of 80 and maximum of 150 charts were reviewed as this was the typical patient volume in the HBPC program. Basic demographic information was collected and analyzed by calculating FRAX and OST scores. With the results, patients were classified as low or high risk of developing osteoporosis, and whether a DEXA scan should be recommended.

Results

After chart review, 83 patients were enrolled in the FHCC HBPC program during the study period. Out of these, 5 patients were excluded due to hospice or palliative care status, limited life expectancy, or had their osteoporosis managed by another non-HBPC provider. As a result, 78 patients were analyzed to determine their risk of osteoporosis (Figure 2). Most of the patients were white males with a median age of 82 years. A majority of the patients did not have any current or previous treatment with bisphosphonates, 77% had normal vitamin D levels, and only 13% (10) were current smokers; of the male patients only 21% (15) had a previous DEXA scan (Table 3).

The FRAX and OST scores for each male patient were calculated (Table 4). Half the patients were low risk for osteoporosis. Just 20% (14) of the patients were at high risk for osteoporosis, and only 6 of those had DEXA scans. However, if expanding the criteria to OST scores of < 2, then only 24% (10) received DEXA scans. When calculating FRAX scores, 30% (21) had ≥ 9.3% for major osteoporotic fracture risk, and only 19% (4) had received a DEXA scan.

Discussion

Based on the collected data, many of the male HBPC patients have not had an evaluation for osteoporosis despite being in a high-risk population and meeting some of the screening guidelines by various organizations.¹ Based on Diem and colleagues and the 2007 VA report, utilizing OST scores could help capture a subset of patients that would be referred for DEXA scans.^5,12 Of the 60% (42) of patients that met OST scores of < 2, 76% (32) of them could have been referred for DEXA scans for osteoporosis evaluation. However, at the time of publication of this article, 50% (16) of the patients have been discharged from the service without interventions. Of the remaining 16 patients, only 2 were referred for a DEXA scan, and 1 patient had confirmed osteoporosis. Currently, these results have been reviewed by the HBPC provider, and plans are in place for DEXA scan referrals for the remaining patients. In addition, for new patients admitted to the program and during annual reviews, the plan is to use OST scores to help screen for osteoporosis.

Limitations

The HBPC population is often in flux due to discharges as patients pass away, become eligible for long-term care, advance to hospice or palliative care status, or see an improvement in their condition to transition back into the community. Along with patients who are bed-bound, have poor prognosis, and barriers to access (eg, transportation issues), interventions for DEXA scan referrals are often not clinically indicated. During calculations of the FRAX score, documentation is often missing from a patient’s medical chart, making it difficult to answer all questions on the questionnaire. This does increase the utility of the OST score as the calculation is much easier and does not rely on other osteoporotic factors. Despite these restrictions for offering DEXA scans, the HBPC service has a high standard of excellence in preventing falls, a major contributor to fractures. Physical therapy services are readily available, nursing visits are frequent and as clinically indicated, vitamin D levels are maintained within normal limits via supplementation, and medication management is performed at least quarterly among other interventions.

Conclusions

The retrospective chart review of patients in the HBPC program suggests that there may be a lack of standardized screening for osteoporosis in the male patient population. As seen within the data, there is great potential for interventions as many of the patients would be candidates for screening based on the OST score. The tool is easy to use and readily accessible to all health care providers and staff. By increasing screening of eligible patients, it also increases the identification of those who would benefit from osteoporosis treatment. While the HBPC population has access limitations (eg, homebound, limited life expectancy), the implementation of a protocol and extension of concepts from this study can be extrapolated into other PACT clinics at VA facilities. Osteoporosis in the male population is often overlooked, but screening procedures can help reduce health care expenditures.

Osteoporosis is a disease characterized by the loss of bone density.¹ Bone is normally porous and is in a state of flux due to changes in regeneration caused by osteoclast or osteoblast activity. However, age and other factors can accelerate loss in bone density and lead to decreased bone strength and an increased risk of fracture. In men, bone mineral density (BMD) can begin to decline as early as age 30 to 40 years. By age 80 years, 25% of total bone mass may be lost.²

Of the 44 million Americans with low BMD or osteoporosis, 20% are men.¹ This group accounts for up to 40% of all osteoporotic fractures. About 1 in 4 men aged ≥ 50 years may experience a lifetime fracture. Fractures may lead to chronic pain, disability, increased dependence, and potentially death. These complications cause expenditures upward of $4.1 billion annually in North America alone.^3,4 About 80,000 US men will experience a hip fracture each year, one-third of whom will die within that year. This constitutes a mortality rate 2 to 3 times higher than that of women. Osteoporosis often goes undiagnosed and untreated due to a lack of symptoms until a fracture occurs, underlining the potential benefit of preemptive screening.

In 2007, Shekell and colleagues outlined how the US Department of Veterans Affairs (VA) screened men for osteoporosis.⁵ At the time, 95% of the VA population was male, though it has since dropped to 91%.⁶ Shekell and colleagues estimated that about 200,0000 to 400,0000 male veterans had osteoporosis.⁵ Osteoporotic risk factors deemed specific to veterans were excessive alcohol use, spinal cord injury and lack of weight-bearing exercise, prolonged corticosteroid use, and androgen deprivation therapy in prostate cancer. Different screening techniques were assessed, and the VA recommended the Osteoporosis Self-Assessment Tool (OST).⁵ Many organizations have developed clinical guidance, including who should be screened; however, screening for men remains a controversial area due to a lack of any strong recommendations (Table 1).

Endocrine Society screening guidelines for men are the most specific: testing BMD in men aged ≥ 70 years, or if aged 50 to 69 years with an additional risk factor (eg, low body weight, smoking, chronic obstructive pulmonary disease, chronic steroid use).¹ The Fracture Risk Assessment tool (FRAX) score is often cited as a common screening tool. It is a free online questionnaire that provides a 10-year probability risk of hip or major osteoporotic fracture.¹¹ However, this tool is limited by age, weight, and the assumption that all questions are answered accurately. Some of the information required includes the presence of a number of risk factors, such as alcohol use, glucocorticoids, and medical history of rheumatoid arthritis, among others (Table 2). The OST score, on the other hand, is a calculation that does not take into account other risk factors (Figure 1). This tool categorizes the patient into low, moderate, or high risk for osteoporosis.⁸

In a study of 4,000 men aged ≥ 70 years, Diem and colleagues found that OST performed better than FRAX in identifying men who were osteoporotic as well as reducing the proportion of men referred for dual-energy X-ray absorptiometry (DEXA) scan vs universal screening.¹² The mean study participant was aged 76 years, overweight, and had a history of smoking; the majority were white. An OST score of < 2 captured 64% of the total population, 82% of whom had a T-score of < 2.5, which is a diagnostic for osteoporosis. A FRAX score of 9.3% captured 42% of the total population, but only 59% of patients with a T-score of < 2.5.

A 2017 VA Office of Rural Health study examined the utility of OST to screen referred patients aged > 50 years to receive DEXA scans in patient aligned care team (PACT) clinics at 3 different VA locations.¹³ The study excluded patients who had been screened previously or treated for osteoporosis, were receiving hospice care; 1 site excluded patients aged > 88 years. Two of the sites also reviewed the patient’s medications to screen for agents that may contribute to increased fracture risk. Veterans identified as high risk were referred for education and offered a DEXA scan and treatment. In total, 867 veterans were screened; 19% (168) were deemed high risk, and 6% (53) underwent DEXA scans. The study noted that only 15 patients had reportable DEXA scans and 10 were positive for bone disease.

As there has been documented success in the PACT setting in implementing standardized protocols for screening and treating veterans, it is reasonable to extend the concept into other VA services. The home-based primary care (HBPC) population is especially vulnerable due to the age of patients, limited weight-bearing exercise to improve bone strength, and limited access to DEXA scans due to difficulty traveling outside of the home. Despite these issues, a goal of the HBPC service is to provide continual care for veterans and improve their health so they may return to the community setting. As a result, patients are followed frequently, providing many opportunities for interventions. This study aims to determine the proportion of HBPC patients who are at high risk for osteoporosis and can receive a DEXA scan for evaluation.

Methods

This study was a retrospective chart analysis using descriptive statistics. It was reviewed and approved by the institutional review board at Captain James A. Lovell Federal Health Care Center (FHCC). Patients were included in the study if they were enrolled in the HBPC program at FHCC. Patients were excluded if they were receiving hospice or palliative care, had a limited life expectancy per the HBPC provider, or had a diagnosis of osteoporosis that was being managed by a VA endocrinologist, rheumatologist, or non-VA provider.

The study was conducted from February 1, 2018, through November 30, 2018. All chart reviews were done through the FHCC electronic health record. A minimum of 80 and maximum of 150 charts were reviewed as this was the typical patient volume in the HBPC program. Basic demographic information was collected and analyzed by calculating FRAX and OST scores. With the results, patients were classified as low or high risk of developing osteoporosis, and whether a DEXA scan should be recommended.

Results

After chart review, 83 patients were enrolled in the FHCC HBPC program during the study period. Out of these, 5 patients were excluded due to hospice or palliative care status, limited life expectancy, or had their osteoporosis managed by another non-HBPC provider. As a result, 78 patients were analyzed to determine their risk of osteoporosis (Figure 2). Most of the patients were white males with a median age of 82 years. A majority of the patients did not have any current or previous treatment with bisphosphonates, 77% had normal vitamin D levels, and only 13% (10) were current smokers; of the male patients only 21% (15) had a previous DEXA scan (Table 3).

The FRAX and OST scores for each male patient were calculated (Table 4). Half the patients were low risk for osteoporosis. Just 20% (14) of the patients were at high risk for osteoporosis, and only 6 of those had DEXA scans. However, if expanding the criteria to OST scores of < 2, then only 24% (10) received DEXA scans. When calculating FRAX scores, 30% (21) had ≥ 9.3% for major osteoporotic fracture risk, and only 19% (4) had received a DEXA scan.

Discussion

Based on the collected data, many of the male HBPC patients have not had an evaluation for osteoporosis despite being in a high-risk population and meeting some of the screening guidelines by various organizations.¹ Based on Diem and colleagues and the 2007 VA report, utilizing OST scores could help capture a subset of patients that would be referred for DEXA scans.^5,12 Of the 60% (42) of patients that met OST scores of < 2, 76% (32) of them could have been referred for DEXA scans for osteoporosis evaluation. However, at the time of publication of this article, 50% (16) of the patients have been discharged from the service without interventions. Of the remaining 16 patients, only 2 were referred for a DEXA scan, and 1 patient had confirmed osteoporosis. Currently, these results have been reviewed by the HBPC provider, and plans are in place for DEXA scan referrals for the remaining patients. In addition, for new patients admitted to the program and during annual reviews, the plan is to use OST scores to help screen for osteoporosis.

Limitations

The HBPC population is often in flux due to discharges as patients pass away, become eligible for long-term care, advance to hospice or palliative care status, or see an improvement in their condition to transition back into the community. Along with patients who are bed-bound, have poor prognosis, and barriers to access (eg, transportation issues), interventions for DEXA scan referrals are often not clinically indicated. During calculations of the FRAX score, documentation is often missing from a patient’s medical chart, making it difficult to answer all questions on the questionnaire. This does increase the utility of the OST score as the calculation is much easier and does not rely on other osteoporotic factors. Despite these restrictions for offering DEXA scans, the HBPC service has a high standard of excellence in preventing falls, a major contributor to fractures. Physical therapy services are readily available, nursing visits are frequent and as clinically indicated, vitamin D levels are maintained within normal limits via supplementation, and medication management is performed at least quarterly among other interventions.

Conclusions

The retrospective chart review of patients in the HBPC program suggests that there may be a lack of standardized screening for osteoporosis in the male patient population. As seen within the data, there is great potential for interventions as many of the patients would be candidates for screening based on the OST score. The tool is easy to use and readily accessible to all health care providers and staff. By increasing screening of eligible patients, it also increases the identification of those who would benefit from osteoporosis treatment. While the HBPC population has access limitations (eg, homebound, limited life expectancy), the implementation of a protocol and extension of concepts from this study can be extrapolated into other PACT clinics at VA facilities. Osteoporosis in the male population is often overlooked, but screening procedures can help reduce health care expenditures.

Osteoporosis is a disease characterized by the loss of bone density.¹ Bone is normally porous and is in a state of flux due to changes in regeneration caused by osteoclast or osteoblast activity. However, age and other factors can accelerate loss in bone density and lead to decreased bone strength and an increased risk of fracture. In men, bone mineral density (BMD) can begin to decline as early as age 30 to 40 years. By age 80 years, 25% of total bone mass may be lost.²

Of the 44 million Americans with low BMD or osteoporosis, 20% are men.¹ This group accounts for up to 40% of all osteoporotic fractures. About 1 in 4 men aged ≥ 50 years may experience a lifetime fracture. Fractures may lead to chronic pain, disability, increased dependence, and potentially death. These complications cause expenditures upward of $4.1 billion annually in North America alone.^3,4 About 80,000 US men will experience a hip fracture each year, one-third of whom will die within that year. This constitutes a mortality rate 2 to 3 times higher than that of women. Osteoporosis often goes undiagnosed and untreated due to a lack of symptoms until a fracture occurs, underlining the potential benefit of preemptive screening.

In 2007, Shekell and colleagues outlined how the US Department of Veterans Affairs (VA) screened men for osteoporosis.⁵ At the time, 95% of the VA population was male, though it has since dropped to 91%.⁶ Shekell and colleagues estimated that about 200,0000 to 400,0000 male veterans had osteoporosis.⁵ Osteoporotic risk factors deemed specific to veterans were excessive alcohol use, spinal cord injury and lack of weight-bearing exercise, prolonged corticosteroid use, and androgen deprivation therapy in prostate cancer. Different screening techniques were assessed, and the VA recommended the Osteoporosis Self-Assessment Tool (OST).⁵ Many organizations have developed clinical guidance, including who should be screened; however, screening for men remains a controversial area due to a lack of any strong recommendations (Table 1).

Endocrine Society screening guidelines for men are the most specific: testing BMD in men aged ≥ 70 years, or if aged 50 to 69 years with an additional risk factor (eg, low body weight, smoking, chronic obstructive pulmonary disease, chronic steroid use).¹ The Fracture Risk Assessment tool (FRAX) score is often cited as a common screening tool. It is a free online questionnaire that provides a 10-year probability risk of hip or major osteoporotic fracture.¹¹ However, this tool is limited by age, weight, and the assumption that all questions are answered accurately. Some of the information required includes the presence of a number of risk factors, such as alcohol use, glucocorticoids, and medical history of rheumatoid arthritis, among others (Table 2). The OST score, on the other hand, is a calculation that does not take into account other risk factors (Figure 1). This tool categorizes the patient into low, moderate, or high risk for osteoporosis.⁸

In a study of 4,000 men aged ≥ 70 years, Diem and colleagues found that OST performed better than FRAX in identifying men who were osteoporotic as well as reducing the proportion of men referred for dual-energy X-ray absorptiometry (DEXA) scan vs universal screening.¹² The mean study participant was aged 76 years, overweight, and had a history of smoking; the majority were white. An OST score of < 2 captured 64% of the total population, 82% of whom had a T-score of < 2.5, which is a diagnostic for osteoporosis. A FRAX score of 9.3% captured 42% of the total population, but only 59% of patients with a T-score of < 2.5.

A 2017 VA Office of Rural Health study examined the utility of OST to screen referred patients aged > 50 years to receive DEXA scans in patient aligned care team (PACT) clinics at 3 different VA locations.¹³ The study excluded patients who had been screened previously or treated for osteoporosis, were receiving hospice care; 1 site excluded patients aged > 88 years. Two of the sites also reviewed the patient’s medications to screen for agents that may contribute to increased fracture risk. Veterans identified as high risk were referred for education and offered a DEXA scan and treatment. In total, 867 veterans were screened; 19% (168) were deemed high risk, and 6% (53) underwent DEXA scans. The study noted that only 15 patients had reportable DEXA scans and 10 were positive for bone disease.

As there has been documented success in the PACT setting in implementing standardized protocols for screening and treating veterans, it is reasonable to extend the concept into other VA services. The home-based primary care (HBPC) population is especially vulnerable due to the age of patients, limited weight-bearing exercise to improve bone strength, and limited access to DEXA scans due to difficulty traveling outside of the home. Despite these issues, a goal of the HBPC service is to provide continual care for veterans and improve their health so they may return to the community setting. As a result, patients are followed frequently, providing many opportunities for interventions. This study aims to determine the proportion of HBPC patients who are at high risk for osteoporosis and can receive a DEXA scan for evaluation.

Methods

This study was a retrospective chart analysis using descriptive statistics. It was reviewed and approved by the institutional review board at Captain James A. Lovell Federal Health Care Center (FHCC). Patients were included in the study if they were enrolled in the HBPC program at FHCC. Patients were excluded if they were receiving hospice or palliative care, had a limited life expectancy per the HBPC provider, or had a diagnosis of osteoporosis that was being managed by a VA endocrinologist, rheumatologist, or non-VA provider.

The study was conducted from February 1, 2018, through November 30, 2018. All chart reviews were done through the FHCC electronic health record. A minimum of 80 and maximum of 150 charts were reviewed as this was the typical patient volume in the HBPC program. Basic demographic information was collected and analyzed by calculating FRAX and OST scores. With the results, patients were classified as low or high risk of developing osteoporosis, and whether a DEXA scan should be recommended.

Results

After chart review, 83 patients were enrolled in the FHCC HBPC program during the study period. Out of these, 5 patients were excluded due to hospice or palliative care status, limited life expectancy, or had their osteoporosis managed by another non-HBPC provider. As a result, 78 patients were analyzed to determine their risk of osteoporosis (Figure 2). Most of the patients were white males with a median age of 82 years. A majority of the patients did not have any current or previous treatment with bisphosphonates, 77% had normal vitamin D levels, and only 13% (10) were current smokers; of the male patients only 21% (15) had a previous DEXA scan (Table 3).

The FRAX and OST scores for each male patient were calculated (Table 4). Half the patients were low risk for osteoporosis. Just 20% (14) of the patients were at high risk for osteoporosis, and only 6 of those had DEXA scans. However, if expanding the criteria to OST scores of < 2, then only 24% (10) received DEXA scans. When calculating FRAX scores, 30% (21) had ≥ 9.3% for major osteoporotic fracture risk, and only 19% (4) had received a DEXA scan.

Discussion

Based on the collected data, many of the male HBPC patients have not had an evaluation for osteoporosis despite being in a high-risk population and meeting some of the screening guidelines by various organizations.¹ Based on Diem and colleagues and the 2007 VA report, utilizing OST scores could help capture a subset of patients that would be referred for DEXA scans.^5,12 Of the 60% (42) of patients that met OST scores of < 2, 76% (32) of them could have been referred for DEXA scans for osteoporosis evaluation. However, at the time of publication of this article, 50% (16) of the patients have been discharged from the service without interventions. Of the remaining 16 patients, only 2 were referred for a DEXA scan, and 1 patient had confirmed osteoporosis. Currently, these results have been reviewed by the HBPC provider, and plans are in place for DEXA scan referrals for the remaining patients. In addition, for new patients admitted to the program and during annual reviews, the plan is to use OST scores to help screen for osteoporosis.

Limitations

The HBPC population is often in flux due to discharges as patients pass away, become eligible for long-term care, advance to hospice or palliative care status, or see an improvement in their condition to transition back into the community. Along with patients who are bed-bound, have poor prognosis, and barriers to access (eg, transportation issues), interventions for DEXA scan referrals are often not clinically indicated. During calculations of the FRAX score, documentation is often missing from a patient’s medical chart, making it difficult to answer all questions on the questionnaire. This does increase the utility of the OST score as the calculation is much easier and does not rely on other osteoporotic factors. Despite these restrictions for offering DEXA scans, the HBPC service has a high standard of excellence in preventing falls, a major contributor to fractures. Physical therapy services are readily available, nursing visits are frequent and as clinically indicated, vitamin D levels are maintained within normal limits via supplementation, and medication management is performed at least quarterly among other interventions.

Conclusions

The retrospective chart review of patients in the HBPC program suggests that there may be a lack of standardized screening for osteoporosis in the male patient population. As seen within the data, there is great potential for interventions as many of the patients would be candidates for screening based on the OST score. The tool is easy to use and readily accessible to all health care providers and staff. By increasing screening of eligible patients, it also increases the identification of those who would benefit from osteoporosis treatment. While the HBPC population has access limitations (eg, homebound, limited life expectancy), the implementation of a protocol and extension of concepts from this study can be extrapolated into other PACT clinics at VA facilities. Osteoporosis in the male population is often overlooked, but screening procedures can help reduce health care expenditures.

Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

Digitalization of patient-specific information over the past 2 decades has dramatically altered health care delivery. Nonetheless, this technology has yet to live up to its promise of improving patient outcomes, in part due to data storage challenges as well as the emphasis on data entry to support administrative and financial goals of the institution.^1-4 Substantially less emphasis has been placed on the retrieval of information required for accurate diagnosis.

A new search engine, Voogle, is now available through Microsoft Internet Explorer (Redmond, WA) to all providers in the US Department of Veterans Affairs (VA) on any intranet-enabled computer behind the VA firewall. Voogle facilitates rapid query-based search and retrieval of patient-specific data in the VA Corporate Data Warehouse (CDW).

Case Example

A veteran presented requesting consideration for implantation of a new device for obstructive sleep apnea. Guidelines for implantation of the new device specify a narrow therapeutic window, so determination of his apnea-hypopnea index (AHI) was critical. The patient had received care at more than 20 VA facilities and knew the approximate year the test had been performed at a non-VA facility.

A health care provider (HCP) using Voogle from his VA computer indexed all Veterans Information Systems and Technology Architecture (VistA) notes for the desired date range. The indexing of > 200 notes was completed in seconds. The HCP opened the indexed records with Voogle and entered a query for “sleep apnea,” which displayed multiple instances of the term within the patient record notes. A VA HCP had previously entered the data from the outside sleep study into a note shortly after the study.

This information was found immediately by sorting the indexed notes by date. The total time required by Voogle to find and display the critical information from the sleep study entered at a different VA more than a dozen years earlier was about 1 minute. These data provided the information needed for decision making at the time of the current patient encounter, without which repeat (and unnecessary) testing would have been required.

Information Overload

Electronic health records (EHRs) such as VistA, upload, store, collate, and present data in near real-time across multiple locations. Although the availability of these data can potentially reduce the risk of error due to missing critical information, its sheer volume limits its utility for point-of-care decision making. Much patient-specific text data found in clinical notes are recorded for administrative, financial, and business purposes rather than to support patient care decision making.^1-3 The majority of data documents processes of care rather than HCP observations, assessment of current status, or plans for care. Much of this text is inserted into templates, consists of imported structured data elements, and may contain repeated copy-and-paste free text.

Data uploaded to the CDW are aggregated from multiple hospitals, each with its own “instance” of VistA. Often the CDW contains thousands of text notes for a single patient. This volume of text may conceal critical historical information needed for patient care mixed with a plethora of duplicated or extraneous text entered to satisfy administrative requirements. The effects of information overload and poor system usability have been studied extensively in other disciplines, but this science has largely not been incorporated into EHR design.^1,3,4

A position paper published recently by the American College of Physicians notes that physician cognitive work is adversely impacted by the incorporation of nonclinical information into the EHR for use by other administrative and financial functions.²

Information Chaos

Beasley and colleagues noted that information in an EHR needed for optimal care may be unavailable, inadequate, scattered, conflicting, lost, or inaccurate, a condition they term information chaos.⁵ Smith and colleagues reported that decision making in 1 of 7 primary care visits was impaired by missing critical information. Surveyed HCPs estimated that 44% of patients with missing information may receive compromised care as a result, including delayed or erroneous diagnosis and increased costs due to duplication of diagnostic testing.⁶

Even when technically available, the usability of patient-specific data needed for accurate diagnosis is compromised if the HCP cannot find the information. In most systems data storage paradigms mirror database design rather than provider cognitive models. Ultimately, the design of current EHR interaction paradigms squanders precious cognitive resources and time, particularly during patient encounters, leaving little available for the cognitive tasks necessary for accurate diagnosis and treatment decisions.^1,3,4,7

VA Corporate Data Warehouse

VistA was implemented as a decentralized system with 130 instances, each of which is a freestanding EHR. However, as all systems share common data structures, the data can be combined from multiple instances when needed. The VA established a CDW more than 15 years ago in order to collate information from multiple sites to support operations as well as to seek new insights. The CDW currently updates nightly from all 130 EHR instances and is the only location in which patient information from all treating sites is combined. Voogle can access the CDW through the Veterans Informatics and Computing Infrastructure (VINCI), which is a mirror of the CDW databases and was established as a secure research environment.

The CDW contains information on 25 million veterans, with about 15 terabytes of text data. Approximately 4 billion data points, including 1 million text notes, are accrued nightly. The Integrated Control Number (ICN), a unique patient identifier, is assigned to each CDW record and is cross-indexed in the master patient index. All CDW data are tied to the ICN, facilitating access to and attribution of all patient data from all VA sites. Voogle relies on this identifier to build indexed files, or domains (which are document collections), of requested specific patient information to support its search algorithm.

Structured Data

Most of the data accrued in an EHR are structured data (such as laboratory test results and vital signs) and stored in a defined database framework. Voogle uses iFind (Intersystems Inc, Cambridge, MA) to index, count, and then search for requested information within structured data fields.

Unstructured Text

In contrast to structured data, text notes are stored as documents that are retrievable by patient, author, date, clinic, as well as numerous other fields. Unstructured (free) text notes are more information rich than either structured data or templated notes since their narrative format more closely parallels providers’ cognitive processes.^1,7 The value of the narrative becomes even more critical in understanding complex clinical scenarios with multiple interacting disease processes. Narratives emphasize important details, reducing cognitive overload by reducing the salience of detail the author deems to be less critical. Narrative notes simultaneously assure availability through the use of unstandardized language, often including specialty and disease-specific abbreviations.¹ Information needed for decision making in the illustrative case in this report was present only in HCP-entered free-text notes, as the structured data from which the free text was derived were not available.

Search

The introduction of search engines can be considered one of the major technologic disruptors of the 21st century.⁸ However, this advance has not yet made significant inroads into health care, despite advances in other domains. As of 2019, EHR users are still required to be familiar with the system’s data and menu structure in order to find needed information (or enter orders, code visits, or any of a number of tasks). Anecdotally, one of the authors (David Eibling) observed that the most common question from his trainees is “How do you . . .?” referring not to the care of the patient but rather to interaction with the EHR.

What is needed is a simple query-based application that finds the data on request. In addition to Voogle, other advances are being made in this arena such as the EMERSE, medical record search engine (project-emerse.org). Voogle was released to VA providers in 2017 and is available through the Internet Explorer browser on VA computers with VA intranet access. The goal of Voogle is to reduce HCP cognitive load by reducing the time and effort needed to seek relevant information for the care of a specific patient.

Natural Language Processing

Linguistic analysis of text seeking to understand its meaning constitutes a rapidly expanding field, with current heavy emphasis on the role of artificial intelligence and machine learning.¹ Advances in processing both structured data and free-text notes in the health care domain is in its infancy, despite the investment of considerable resources. Undoubtedly, advances in this arena will dramatically change provider cognitive work in the next decades.

VistA is coded in MUMPS (Massachusetts General Hospital Utility Multi-Programming System, also known as M), which has been in use for more than 50 years. Voogle employs iKnow, a novel natural language processing (NLP) application that resides in Caché (Intersystems, Boston, MA), the vendor-supported MUMPS infrastructure VistA uses to perform text analysis. iKnow does not attempt to interpret the meaning of text as do other common NLP applications, but instead relies on the expert user to interpret the meaning of the analyzed text. iKnow initially divides sentences into relations (usually verbs) and concepts, and then generates an index of these entities. The efficiency of iKnow results in very rapid indexing—often several thousand notes (not an uncommon number) can be indexed in 20 to 30 seconds. iKnow responds to a user query by searching for specific terms or similar terms within the indexed text, and then displays these terms within the original source documents, similar to well-known commercial search engines. Structured data are indexed by the iFind program simultaneously with free-text indexing (Figure 1).

Security

Maintaining high levels of security of Health Insurance Portability and Accountability (HIPAA)-compliant information in an online application such as Voogle is critical to ensure trust of veterans and HCPs. All patient data accessed by Voogle reside within the secure firewall-protected VINCI environment. All moving information is protected with high-level encryption protocols (transport layer security [TLS]), and data at rest are also encrypted. As the application is online, no data are stored on the accessing device. Voogle uses a secure Microsoft Windows logon using VA Active Directory coupled with VistA authorization to regulate who can see the data and use the application. All access is audited, not only for “sensitive patients,” but also for specific data types. Users are reminded of this Voogle attribute on the home screen.

Accessing Voogle

Voogle is available on the VA intranet to all authorized users at https://voogle.vha.med.va.gov/voogle. To assure high-level security the application can only be accessed with the Internet Explorer browser using established user identification protocols to avoid unauthorized access or duplicative log-in tasks.

Indexing

Indexing is user-driven and is required prior to patient selection and term query. The user is prompted for a patient identifier and a date range. The CDW unique patient identifier is used for all internal processing. However, a social security number look-up table is incorporated to facilitate patient selection. The date field defaults to 3 years but can be extended to approximately the year 2000.

Queries

Entering the patient name in Lastname, Firstname (no space) format will yield a list of indexed patients. All access is audited in order to deter unauthorized queries. Data from a demonstration patient are displayed in Figures 2, 3, 4, 5,
and 6.

Structured Data Searches

Structured data categories that contain the queried term, as well as a term count, are displayed after the “Structured Data” toggle is selected (Figure 2). After the desired category (Figure 2: “Outpatient Rx”) is selected, Voogle accesses the data file and displays it as a grid (medication list, Figure 3). Filter and sort functions enable display of specific medications, drug classes, or date ranges (Figure 4).

Display of Terms Within Text Notes

Selecting a term from the drop-down list (Figure 5) opens a grid with the term highlighted in a snippet of text (Figure 6). Opening the document displays the context of the term, along with negation terms (ie, not, denies, no, etc) in red font if present. Voogle, unlike other NLP tools that attempt to interpret medical notes, relies on interpretation by the HCP user. Duplicate note fragments will be displayed in multiple notes, often across multiple screens, vividly demonstrating the pervasive use of the copy-and-paste text-entry strategy. Voogle satisfies 2 of the 4 recommendations of the recent report on copy-and-paste by Tsou and colleagues.⁹ The Voogle text display grid identifies copy-and-pasted text as well as establishes the provenance of the text (by sorting on the date column). Text can be copied from Voogle into an active Computerized Patient Record System (CPRS) note if needed for active patient care. Reindexing the following day and then repeating the search will demonstrate the newly copied-and-pasted text appended to the sequence.

Limitations

Voogle is unable to access all VA patient data currently. There are a dozen or so clinical domains that are indexed by Voogle that include prescriptions, problem lists, health factors, and others. More domains can be added with minimal effort and would then be available for fast search. The most critical deficiency is its inability to access, index, or query text reports stored as images within VistA Imaging. This includes nearly all reports from outside HCPs, emergency department visits or discharge summaries from unlinked hospitals, anesthesia reports, intensive care unit flow sheets, electrocardiograms, as well as numerous other text reports such as pulmonary function reports or sleep studies. Information that is transcribed by the provider into VistA as text (as in the case presented) is available within the CDW and can be found and displayed by Voogle search.

Voogle requires that the user initiates the indexing process prior to initiating the search process. Although Voogle defaults to 3 years prior to the current date, the user can specify a start date extending to close to the year 2000. The volume of data flowing into the CDW precludes automatic indexing of all patient data, as well as automatic updating of previously indexed data. We have explored the feasibility of queueing scheduled appointments for the following day, and although the strategy shows some promise, avoiding conflict with user-requested on-demand indexing remains challenging.

The current VA network architecture updates the CDW every night, resulting in up to a 24-hour delay in data availability. However, this delay should be reduced to several minutes after implementation of real-time data feeds accompanying the coming transition to a new EHR platform.

Conclusions

The recent introduction of the Joint Legacy Viewer (JLV) to the VA EHR desktop has enhanced the breadth of patient-specific information available to any VHA clinician, with recent enhancements providing access to some community care notes from outside HCPs. Voogle builds on this capability by enabling rapid search of text notes and structured data from multiple VA sites, over an extended time frame, and perhaps entered by hundreds of authors, as demonstrated in the case example. Formal usability and workload studies have not been performed; however, anecdotal reports indicate the application dramatically reduces the time required to search for critical information needed for care of complex patients who have been treated in multiple different VA hospitals and clinics.

The Voogle paradigm of leveraging patient information stored within a large enterprise-wide data warehouse through NLP techniques may be applicable to other systems as well, and warrants exploration. We believe that replacing traditional data search paradigms that require knowledge of data structure with a true query-based paradigm is a potential game changer for health information systems. Ultimately this strategy may help provide an antidote for the information chaos impacting HCP cognition. Moreover, reducing HCP cognitive load and time on task may lessen overall health care costs, reduce provider burn-out, and improve the quality of care received by patients.

Near real-time data feeds and adding additional clinical domains will potentially provide other benefits to patient care. For example, the authors plan to investigate whether sampling incoming data may assist with behind-the-scenes continuous monitoring of indicators of patient status to facilitate early warning of impending physiologic collapse.¹⁰ Other possible applications could include real-time scans for biosurveillance or other population screening requirements.

Acknowledgments
The authors express their sincere appreciation to Leslie DeYoung for documentation and Justin Wilson who constructed much of the graphical user interface for the Voogle application and design. Without their expertise, passion, and commitment the application would not be available as it is now.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

On the 11th day of the 11th month, we celebrate Veterans Day (no apostrophe because it is not a day that veterans possess or that belongs to any individual veteran).^2,3 Interestingly, the US Department of Defense (DoD) and the US Department of Veterans Affairs (VA) have web pages correcting any confusion about the meaning of Memorial Day and Veterans Day so that the public understands the unique purpose of each holiday. Memorial Day commemorates all those who lost their lives in the line of duty to the nation, whereas Veterans Day commemorates all those who have honorably served their country as service members. While Memorial Day is a solemn occasion of remembering and respect for those who have died, Veterans Day is an event of gratitude and appreciation focused on veterans still living. The dual mission of the 2 holidays is to remind the public of the debt of remembrance and reverence we owe all veterans both those who have gone before us and those who remain with us.

Memory is what most intrinsically unites the 2 commemorations. In fact, in Great Britain, Canada, and Australia, November 11 is called Remembrance Day.² Yet memory is a double-edged sword that can be raised in tribute to service members or can deeply lacerate them. Many of the wounds that cause the most prolonged and deepest suffering are not physical—they are mental. Disturbances of memory are among the criteria for posttraumatic stress disorder (PTSD). Under its section on intrusive cluster, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) lists “recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).” The avoidance cluster underscores how the afflicted mind tries to escape itself: “Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).”⁴

PTSD was first recognized as a psychiatric diagnosis in DSM-III in 1980, and since then VA and DoD have devoted enormous resources to developing effective treatments for the disorder, most notably evidence-based psychotherapies. Sadly ironic, the only psychiatric disorder whose etiology is understood has proved to be the most difficult to treat much less cure. As with most serious mental illnesses, some cases become chronic and refractory to the best of care. These tormented individuals live as if in a twilight zone between the past and the present.

Memory and war have a long history in literature, poetry, and history. Haunting memories of PTSD are found in the ancient epics of Homer. On the long treacherous journey home from sacking Troy, Odysseus and his army arrive in the land of the Lotus-eaters, where native sweet fruit induces a state of timeless forgetfulness in which torment and tragedy dissolve along with motivation and meaning.⁵ Jonathan Shay, VA psychiatrist and pioneer of the Homer-PTSD connection, suggested the analogy between the land of the Lotus-eaters and addiction: Each is a self-medication of the psychic aftermath of war.⁶

But what if those devastating memories could be selectively erased or even better blocked before they were formed? Although this solution may seem like science fiction, research into these possibilities is in reality science fact. Over the past decades, the DoD and the VA have sought such a neuroscience jewel in the lotus. Studies in rodents and humans have looked at the ability of a number of medications, most recently β blockers, such as propranolol, to interfere with the consolidation of emotionally traumatic memories (memory erasure) and disrupting their retention once consolidated (memory extinction).⁷ While researchers cannot yet completely wipe out a selected memory, like in the movie Star Trek, it has been shown that medications at least in study settings do reduce fear and can attenuate the development of PTSD when combined with psychotherapy. Neuroscientists call these more realistic alterations of recall memory dampening. Though these medications are not ready for regular clinical application, the unprecedented pace of neuroscience makes it nearly inevitable that in the not so distant future some significant blunting of traumatic memory will be possible.

Once science answers in the affirmative the question, “Is this intervention something we could conceivably do?” The next question belongs to ethics, “Is this intervention something we should do even if we can?” As early as 2001, the President’s Council on Bioethics answered the latter with “probably not.”

Use of memory-blunters at the time of traumatic events could interfere with the normal psychic work and adaptive value of emotionally charged memory....Thus, by blunting the emotional impact of events, beta-blockers or their successors would concomitantly weaken our recollection of the traumatic events we have just experienced. Yet often it is important in the after of such events that at least someone remember them clearly. For legal reasons, to say nothing of deeper social and personal ones, the wisdom of routinely interfering with the memories of traumatic survivors and witnesses is highly questionable.⁸

Many neuroscientists and neuroethicists objected to the perspective of the Bioethics Council as being too puritanical and its position overly pessimistic:

Whereas memory dampening has its drawbacks, such may be the price we pay in order to heal immense suffering. In some contexts, there may be steps that ought to be taken to preserve valuable factual or emotional information contained in memory, even when we must delay or otherwise impose limits on access to memory dampening. None of these concerns, however, even if they find empirical support, are strong enough to justify brushed restrictions on memory dampening.⁹

The proponents of the 2 views propose and oppose the contrarian position on issues both philosophical and practical, such as the function of traumatic experience in personal growth; how the preservation of memory is related to the integrity of the person and authenticity of the life lived; how blunting of memories of especially combat trauma may normalize our reactions to suffering and evil; and most important for this Veterans Day essay, whether remembering is an ethical duty and if so whose is it to discharge, the individual, his family, community, or country.

More pragmatic, there would be a need to refine our understanding of the risk factors for chronic and disabling PTSD; to determine when in the course of the trauma experience to pharmacologically interfere with memory and to what degree and scope; how to protect the autonomy of the service member to consent or to refuse the procedure within the recognized confines of military ethics; and most important for this essay, how to prevent governments, corporations, or any other entity from exploiting neurobiologic discoveries for power or profit.

Elie Wiesel is an important modern prophet of the critical role of memory in the survival of civilization. His prophecy is rooted in the incomprehensible anguish and horror he personally and communally witnessed in the Holocaust. He suggests in this editorial’s epigraph that there are deep and profound issues to be pondered about memory and its inextricable link to suffering. Meditations offer thoughts, not answers, and I encourage readers to spend a few minutes considering the solemn ones presented here this Veterans Day.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

When we studied the knowledge and practice of e-cigarette use among pregnant women in one of our outpatient practices, we found that 43% of more than 300 survey participants believed e-cigarettes are less harmful to a fetus than traditional cigarettes. Just over half – 57% – believed that e-cigarettes contain nicotine.

This study from 5 years ago demonstrated the need for more patient education.¹ Today, we have even more clarity that, while there may be health benefits of switching to noncombustible forms of nicotine consumption outside of pregnancy, these potential benefits do not extend to pregnancy. Both human and animal studies have demonstrated that nicotine itself is harmful to the developing fetus; the Centers for Disease Control and Prevention warns against the use of e-cigarettes in pregnancy for this reason.

A 2018 literature review on the use of e-cigarettes in pregnancy and the effects on perinatal/neonatal outcomes reported that the amount of nicotine consumed by e-cigarette users is similar to that of cigarette smokers and that most animal studies suggest a potential danger to the fetus, primarily because of the nicotine.² Effects on the immune system, neural development, lung function, and cardiac function were all noted in the review. Other research has shown that e-cigarette fluid can contain formaldehyde and other harmful substances.

A new analysis of data from the 2014-2017 National Health Interview Survey shows a significantly lower prevalence of conventional cigarette use among pregnant women than in nonpregnant women, and an almost identical prevalence of e-cigarette use among pregnant and nonpregnant women of reproductive age.³ This discrepancy again suggests that women may not be aware of the potential harms of e-cigarettes in pregnancy, which is not surprising considering that prenatal care clinicians often are not appropriately screening or counseling regarding e-cigarette use.⁴

We must specifically ask about vaping and e-cigarette use as part of our prenatal care and counsel women that the use of e-cigarettes is not a safer alternative to cigarette smoking. I urge patients who have switched to e-cigarettes as a means of smoking cessation or as a choice they perceive to be safer to work together with me to find another way to reduce potential harm to their baby.

References

1. J Addict Med. 2015 Jul-Aug;9(4):266-72.

2. Obstet Gynecol Surv. 2018 Sep;73(9):544-9.

3. JAMA Pediatr. 2019 Jun 1;173(6):600-2.

4. Am J Obstet Gynecol. 2014 Dec;211(6):695.e1-7.

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

We know that the environment significantly impacts our health. People who live in areas prone to industrial waste, poor air or water quality, and crime have higher risks for cardiovascular disease, severe asthma, and stress-induced illnesses. Children who grow up under these conditions can experience a failure to thrive.

As ob.gyns., we also recognize that the intrauterine environment plays a key role in influencing embryonic and fetal development. For this reason, we counsel our pregnant patients to eat well-balanced diets, drink healthy amounts of water, get plenty of rest, and incorporate physical activity into their daily routines. Indeed, the seminal work by Sir David Barker demonstrated that the roots of chronic diseases – including hypertension, stroke, and type 2 diabetes – begin in utero. We truly are where we live – from before birth up through adulthood.

Because the womb environment, where we spend the first critical 9 months of life, dramatically affects our lifelong health, we advise against the use of certain medications and other substances during pregnancy. Some of these recommendations seem clear-cut: Don’t smoke and significantly reduce or abstain from alcohol consumption; illicit drugs – such as cocaine or heroin – should never be used. However, gray areas exist. For example, although anticonvulsants carry higher risks for congenital malformations, patients who experience seizures may need to continue taking antiepileptic drugs during pregnancy, especially those with long safety records.

One of the newer challenges the medical community in general must face is the broadened use and wider societal acceptance of cannabis. Currently legal in 33 U.S. states and Washington, D.C., medical marijuana now is viewed as another legitimate tool in the health care arsenal, rather than the off-limits, off-label substance it was less than a generation ago.

Although proponents may tout the health benefits of cannabis and related products like cannabidiol, it remains unclear what the long-term effects of routine use may have on development, especially fetal development. Research in this area still is relatively new, but data indicate that more harm than good may come from cannabis exposure during pregnancy. However, how we as ob.gyns. navigate conversations with our patients around substance use remains crucial to our delivery of the best possible prenatal care.

We have invited Katrina S. Mark, MD, associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, to examine use of cannabis in pregnancy and the need for maintaining trust in the patient-practitioner relationship when discussing substance use during prenatal counseling.
 

Dr. Reece, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland School of Medicine as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He is the medical editor of this column. He said he had no relevant financial disclosures. Contact him at [email protected].

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

A flurry of research papers published this year has simultaneously documented a rise in the use of cannabis during pregnancy and offered more data about its potential harms. This confluence of findings is concerning and highlights the importance of screening our patients for cannabis use and engaging with them in a way in which we can maintain their trust and their commitment to prenatal care.

Stuart Jenner/Thinkstock

A retrospective cohort study involving 661,617 women in Ontario found a significant association between self-reported cannabis use in pregnancy and an increased risk of preterm birth (relative risk, 1.41), as well as a greater likelihood of small-for-gestational-age babies (RR, 1.53), placental abruption (RR, 1.72), and transfer to neonatal intensive care (RR, 1.40).¹ The study, reported in JAMA in July 2019, carefully matched users with nonusers who had the same characteristics – for example, tobacco use or not.

This new information builds upon other meta-analyses that have demonstrated a decrease in birth weight and greater admittance to the neonatal ICU associated with cannabis use in pregnancy – and it supplements what some research suggests about long-term neurologic development and a potentially increased risk of attention and behavioral problems. Other outcomes that have been noted in long-term neurologic studies of children who were exposed to cannabis in utero include impaired visual acuity, verbal reasoning and comprehension, and short-term memory.²

Increases in use were recently documented in two studies. One, an analysis of data from the National Survey on Drug Use and Health (NSDUH) published in JAMA in June 2019, showed that, between 2002-2003 and 2016-2017, the use of cannabis “in the past month” increased from 3.4% to 7.0% among pregnant women overall, and from 6% to 12% during the first trimester.³

The use of cannabis on a daily or near-daily basis, moreover, increased from 0.9% to 3% among pregnant women overall and from 2% to 5% during the first trimester. The data were collected during face-to-face interviews and were adjusted for age, race/ethnicity, and family income.

In the second study – a cross-sectional study of 367,403 pregnancies among women who filled out a questionnaire on cannabis use during standard prenatal care at Kaiser Permanente Northern California – the adjusted prevalence of use in the year before pregnancy increased from 7% in 2009 to 13% in 2017, and the adjusted prevalence during pregnancy increased from 2% to 3%.⁴

As in the NSDUH analysis, daily use increased most rapidly (compared with weekly or monthly) such that, by 2017, 25% of those who reported using cannabis in the year before pregnancy – and 21% of those who used cannabis during pregnancy – were daily users. It is notable that Kaiser’s population is diverse in all respects, and that the annual relative rates of increase in cannabis use before and during pregnancy (at each level of frequency) were consistent across racial/ethnic and household income groups.

It’s also worth noting that, in earlier research covering a similar time period (2009-2016), the investigators found significant increases in use via urine toxicology testing that occurs at the first prenatal visit at Kaiser. The increase found through questionnaires, therefore, reflects more than a greater willingness to self-report.

Choosing a screening tool

Universal prenatal substance use screening is recommended by the American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention, but we don’t have any specific recommendations on what this means. Who should be screening, and what should that screening look like? Should we use a biologic screen, a standardized screening tool, or simply ask patients whether they use illicit substances?

Screening tools seem advantageous in that they are low cost, noninvasive, potentially comprehensive, and not subject to false-positive results as biologic screens can be – but which tool or tools are best? There are several validated screening tools that can be used outside of pregnancy to determine an individual’s use of illicit substances and whether or not that use is problematic, but previous studies have not used biologic markers to validate substance use screeners in pregnancy. Nor have studies compared screeners in pregnancy.

In our prenatal population in Baltimore, we have not been getting the answers we want using various nonvalidated screening tools. Approximately 30% of patients are positive for cannabis by urine screen, but only half tell us about their use.

Through research in our two prenatal care practices (one serving mostly privately insured and the other serving primarily Medicaid-eligible patients), we assessed both the accuracy and the acceptability of three substance use screening tools that are brief and that have been validated (for the general population) by the World Health Organization for screening of multiple substances: the 4P’s Plus (Parents, Partner, Past, and Pregnancy), the National Institute on Drug Abuse Quick Screen–ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile–Pregnancy) scale.

In one study, published in May 2019 in Obstetrics & Gynecology, we recruited 500 pregnant women and administered these three tests to each of them.⁵ We then compared results with those of urine and hair drug testing, and checked the test-retest reliability of each test by readministering them (albeit by telephone) a week later. Although hair testing is not an indicator of current substance use, we used it to validate the screening tools on less-recent use.

The tests with the highest sensitivity and negative predictive values – the qualities we most want for screening – were the SURP-P and the 4P’s Plus (sensitivity of 92.4% and 90.2%, respectively). Overall they were highly sensitive screening tools across all trimesters, races, and age groups, making them more ideal screening tests than the NIDA Quick Screen–ASSIST.

Of the two tests, the 4P’s Plus screening tool was the one preferred by staff from both practices. In a companion qualitative study, we conducted focus-group discussions with 40 practice staff who were responsible for administering or overseeing patient screening.⁶ The staff, who were unaware of the sensitivity findings, were asked what they thought about the acceptability to patients of each of the three tools and their usability in practice.

Most of the participating staff preferred the 4P’s Plus screening tool for several reasons: It is easy to understand, is brief and to the point, and it has nonjudgmental language and tone. The screener first asks the patient about her parents’ and her partner’s use of alcohol and drugs, and then asks the patient about her own use of alcohol and tobacco. Affirmative responses to these questions lead to additional questions.

The premise is that one’s genetics, history, and current exposures – as well as one’s own use of tobacco and alcohol – are significantly associated with the use of illicit substances. If the patient reports no parental history or partner usage, and has never drank or smoked before, it’s extremely unlikely that she is using other drugs. The progression of questions does indeed seem less judgmental than immediately asking: “Do you use drugs?”

For us, the insight from this staff perception study combined with the findings on accuracy mean that the 4P’s Plus may be the most useful and acceptable screening tool for routine use in prenatal care.

Talking with our patients

The increase in the use of cannabis before and after pregnancy parallels the movement toward state legalization and decriminalization. Historically, clinicians often have relied on illegality as their main focus of counseling when giving recommendations for cessation and abstinence in pregnancy.² This approach not only leads to punitive counseling, which can fracture the doctor-patient relationship, but increasingly it is no longer valid. In our changing legal climate, we need to provide medically based counseling and be very clear with our patients that legalization does not equate to safety.

It is important that we neither minimize nor overstate the risks. The evidence base for adverse birth outcomes of cannabis use in pregnancy is quite robust, but the associations can be subtle and are moderated by other behaviors and environmental factors that continue to challenge researchers.

As with alcohol, there likely are dose-or trimester-dependent differences in perinatal outcomes, and it’s quite possible that different cannabis products and routes of consumption have different effects. At this point, however, we don’t know the full story, nor do we know the extent to which the literature is biased toward positive correlations – the reporting of adverse effects – compared with negative findings. It is our job as medical care providers to be comfortable in that gray area and to still counsel patients on what we do know, providing the best-possible medical advice based on the information available to us.

In talking with patients, I explain that cannabis may cause a spectrum of problems and that there certainly are risks. I also tell them that we’re uncertain about the conditions and magnitude of that risk and that some babies who are exposed to cannabis in utero may have no perceivable consequences. Such honesty is important for maintaining trust, especially as some patients may see friends and relatives who also are cannabis users have normal pregnancy outcomes.

Much of my concern about cannabis in pregnancy centers on its effect on the developing brain and on long-term neurologic development. I share this with patients – I tell them that cannabis crosses the placenta and may well affect their baby’s brain as it is developing. I explain that I do not know whether this effect would be big or small, but that it’s not a chance I’m willing to take for their baby.

It is also important to educate patients that cannabis products are untested and unregulated and that they may be contaminated with heavy metals, pesticides, and other toxins that may be harmful to themselves and their babies. Patients also should know that the potency of cannabis has been dramatically increasing; research shows that the tetrahydrocannabinol – the psychoactive component – concentration has tripled over the past 2 decades.⁷

Research tells us that women who use illicit drugs and alcohol categorically engage in some form of harm reduction once they learn they are pregnant, and the same is true for cannabis. This is seen in dramatically different rates of first- and third-trimester use in the new analysis of NSDUH data; third-trimester use is approximately halved.

Some women will not be able to discontinue use, however, or they may try to quit and fail in their attempts. As we should with substance use more broadly, we must meet patients where they are, view cannabis use as a chronic medical problem, offer our assistance in helping them reduce harms of their use, and understand that quitting is a process.

Screening for mental health disorders and trauma is, of course, especially important in patients who use cannabis and other substances recreationally. In cases of medical marijuana usage, I recommend, as ACOG and other have done, that we discuss the risks and benefits of continuing cannabis versus shifting to alternative medications if options exist.

In any case, we must guard against cannabis use dominating all conversations throughout our prenatal care. All patients should be welcomed, congratulated on their pregnancy and on coming for prenatal care, and engaged in the overall process of optimizing their health and the health of their baby. Like any other health issue during pregnancy, cannabis use needs to be screened for and treated in an evidence-based manner, but it does not define the trajectory or success of a woman’s pregnancy or her ability to be a successful parent.

Dr. Mark is associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine.

References

1. JAMA. 2019 Jul 9;322(2):145-52.

2. Preventive Medicine 2017 May 18;104:46-9.

3. JAMA. 2019 Jul 9;322(2):167-9.

4. JAMA Netw Open. 2019 Jul 3;2(7):e196471.

5. Obstet Gynecol. 2019 May;133(5):952-61.

6. J. Addict Med. 2019 May 10. doi: 10.1097/ADM.0000000000000543.

7. Biol Psychiatry. 2016 Apr 1;79(7):613-9.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Antifungal prophylaxis with caspofungin led to a lower incidence of invasive fungal disease, compared with fluconazole, in children and young adults with acute myeloid leukemia (AML), according to new study findings.

National Institutes of Health/Wikimedia Commons/Public Domain

The results suggest caspofungin may be an appropriate prophylactic strategy to prevent invasive fungal disease in younger patients with newly diagnosed AML, reported Brian T. Fisher, DO, of the University of Pennsylvania, Philadelphia, and colleagues. The study was published in JAMA.

The randomized, open-label study included 517 children, adolescents, and young adults with de novo, relapsed, or secondary AML. Study patients received treatment in 115 centers throughout United States and Canada. The median age of patients in the study was 9 years (range, 0-26 years); 56% were male and approximately 69% were white.

Study subjects were randomly assigned to receive antifungal prophylaxis with 70 mg/m² (maximum dose 70 mg/day) of intravenous caspofungin on day 1, followed by 50 mg/m² per day (maximum dose 50 mg/day) thereafter, or age-dosed intravenous or oral fluconazole.

Prophylactic therapy was initiated 24-72 hours after the completion of each chemotherapy cycle, and was maintained until the end of the neutropenic period following each cycle.

At 5-month follow-up, the cumulative incidence rate of probable or proven invasive fungal disease was 3.1% (95% confidence interval, 1.3%-7.0%) in the caspofungin arm, compared with 7.2% (95% CI, 4.4%-11.8%) in the fluconazole arm (overall P = .03).

In addition, the 5-month cumulative incidence rate of probable or proven invasive aspergillosis infection was 0.5% (95%CI, 0.1%-3.5%) in patients who received caspofungin, compared with 3.1% (95% CI, 1.4%-6.9%) in patients who received fluconazole (overall P = .046).

“No statistically significant differences in empirical antifungal therapy or 2-year overall survival were observed,” they reported.

With respect to safety, the most frequently reported adverse events were hypokalemia (22 events in the caspofungin arm vs. 13 in the fluconazole arm), respiratory failure (6 events in the caspofungin arm vs. 9 in the fluconazole arm), and elevated alanine transaminase (4 events in the caspofungin arm vs. 8 in the fluconazole arm).

The researchers acknowledged a key limitation of the study was the short duration of follow-up. As a result, the precision of some comparative measures may have been reduced.

The National Cancer Institute funded the study. The authors reported financial affiliations with Astellas, Celgene, Leadiant Biosciences, Merck, Nabriva Therapeutics, Novartis, Pfizer, Shire, and T2 Biosystems.

SOURCE: Fisher BT et al. JAMA. 2019;322(17):1673-81.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

[email protected]

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

[email protected]

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.

Requests for crowd diagnosis of sexually transmitted diseases were frequent on a social media website, new research found.

The social media website Reddit, which currently has 330 million monthly active users, is home to more than 230 health-related subreddits, including r/STD, a forum that allows users to publicly share “stories, concerns, and questions” about “anything and everything STD related,” Alicia L. Nobles, PhD, of the department of medicine at the University of California, San Diego, and associates wrote in a research letter published in JAMA.

Dr. Noble and associates conducted an analysis of all posts published to r/STD from the subreddit’s inception during November 2010–February 2019, a total of 16,979 posts. Three coauthors independently coded each post, recording whether or not a post requested a crowd diagnosis, and if so, whether that request was made to obtain a second opinion after a visit to a health care professional.

About 58% of posts requested a crowd diagnosis, 31% of which included an image of the physical signs. One-fifth of the requests for a crowd diagnosis were seeking a second opinion after a previous diagnosis by a health care professional. Nearly 90% of all crowd-diagnosis requests received at least one reply (mean responses, 1.7), with a median response time of 3.04 hours. About 80% of requests were answered in less than 1 day.

While crowd diagnoses do seem to be popular and have the benefits of anonymity, rapid response, and multiple opinions, the accuracy of crowd diagnoses is unknown given the limited information responders operate with and the potential lack of responder medical training, the study authors noted. Misdiagnosis could allow further disease transmission, and third parties viewing posts could incorrectly self-diagnose their own condition.

“Health care professionals could partner with social media outlets to promote the potential benefits of crowd diagnosis while suppressing potential harms, for example by having trained professionals respond to posts to better diagnose and make referrals to health care centers,” Dr. Nobles and associates concluded.

One coauthor reported receiving personal fees from Bloomberg and Good Analytics, and another reported receiving grants from the National Institutes of Health; no other disclosures were reported.

[email protected]

SOURCE: Nobles AL et al. JAMA. 2019 Nov 5;322(17):1712-3.