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Sleep disorders in children with ADHD treated with off-label medications
Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.
“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.
Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.
The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.
The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.
Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).
Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.
Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.
Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.
especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.
This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.
“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.
They reported having no disclosures.
SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.
Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.
“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.
Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.
The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.
The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.
Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).
Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.
Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.
Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.
especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.
This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.
“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.
They reported having no disclosures.
SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.
Sleep problems in children diagnosed with attention-deficit/hyperactivity disorder are treated with a variety of medications, many off label for sleep and unstudied for safety and effectiveness in children, a study of Medicaid prescriptions has found.
“Sleep disorders coexist with attention-deficit/hyperactivity disorder (ADHD) for many children and are associated with neuropsychiatric, physiologic, and medication-related outcomes,” wrote Tracy Klein, PhD, of Washington State University, Vancouver, and her colleagues. The report is in the Journal of Pediatric Health Care. These patients can have sleep disordered breathing and behavioral issues occurring around bedtime. Known adverse effects of the stimulant and nonstimulant medications used to treat ADHD can include sleep disturbance, delayed circadian rhythm, insomnia, and somnolence. Yet, research on both sleep problems in children with ADHD and prescribing patterns is scanty, according to the investigators.
Dr. Klein and her colleagues conducted a study aimed at identifying the off-label medications being prescribed to potentiate sleep in children with ADHD, and the characteristics of the children and their prescribers. They used 5 years of pharmacy claims for children in Oregon insured through Medicaid and had a provider diagnosis of ADHD during Jan. 1, 2012, to Dec. 31, 2016. The children were aged 3-18 years and the prescriptions measured were the number of 30-day prescriptions. Prescribers were identified by national provider identifier taxonomies (nurse, physician, other prescriber), and classified as either generalist or specialist. The medications were classified as controlled or uncontrolled as determined by Title 21 of the U.S. Controlled Substances Act.
The data yielded 14,567 prescriptions for 2,518 children for a 30-day supply of medication known to potentiate sleep but off-label for children. Children aged 3-11 years comprised about 38% of these patients. Some children were prescribed more than one of these medications. Medications specifically on label for sleep but not indicated for children were not included. Those medications indicated for comorbid conditions and those indicated for ADHD that specifically cause somnolence were excluded.
The uncontrolled medications prescribed in this sample were amitriptyline, doxepin, hydroxyzine, low-dose quetiapine, and trazodone. The controlled medications identified were clonazepam and lorazepam, and a few prescriptions for phenobarbital.
Most of the prescriptions (63.8%) went to older children aged 12-18 years and most prescriptions (66.3%) went to males. The most commonly prescribed noncontrolled medication was trazodone (5,190 prescriptions), followed by hydroxyzine (2,539), and quetiapine (2,402). The most frequently prescribed controlled medication was clonazepam (2,145), followed by lorazepam (534).
Specialist prescribers wrote most of the prescriptions for this patient group, but no differences were found in prescribing patterns between specialists and generalists.
Dr. Klein and her colleagues noted that 871 unique children were prescribed 5,190 30-day−supply prescriptions for trazodone, including 23 children under age 5. Trazodone is a serotonin modulator indicated for the treatment of major depressive disorder, but has not been studied for safety and efficacy in children and has no Food and Drug Administration indication for children. “Hydroxyzine, quetiapine, and amitriptyline also were prescribed for a large number of children, including some for children as young as 3 years, despite lack of approval for use to induce to sleep and increased potential for significant adverse reactions in children,” they wrote.
Dr. Klein suggested that prescribers receive pressure from families to “do something” for their children, who may be disruptive day and night. “Prescribers may be unaware that trazodone, which is commonly used in practice, has never been approved for treatment of insomnia in children or adults. Insurance may not adequately fund other options, such as extensive behavioral therapy,” she stated in an interview. These medications come with some risk for children, Dr. Klein noted.
especially if their reaction to it is behavioral.” There is also potential for unanticipated drug interactions between off-label medications prescribed for sleep and drugs prescribed to treat ADHD.
This study has limitations related to the absence of detailed clinical explanatory information found in claims data. Information on adherence to treatment and adverse events, for example, is not contained in claims data. The study does not address the overall rates of sleep disorders in children with ADHD nor the percentage of children with ADHD who are prescribed any medication to potentiate sleep but looks at which off-label drugs are being prescribed, to which children, and by whom.
“Most medications prescribed in this study, used to induce sleep or treat insomnia, have not been studied for safety and efficacy in children, and their use should not be extrapolated from adult studies,” the researchers concluded.
They reported having no disclosures.
SOURCE: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.
FROM THE JOURNAL OF PEDIATRIC HEALTH CARE
Key clinical point: The most commonly prescribed off-label medications prescribed to children were trazodone (5,190), hydroxyzine (2,539), quetiapine (2,402), and clonazepam (2,145).
Major finding: Most of the prescriptions (63.8%) went to older children aged 12-18 years, and most prescriptions (66.3%) went to males.
Study details: Medicaid claims data for Jan. 1, 2012, to Dec. 31, 2016, yielding 14,567 prescriptions of off-label medications for 2,518 children.
Disclosures: The investigators reported no disclosures.
Source: Klein T et al. J Pediatr Health Care. 2018 Jan 8. doi: 10.1016/j.pedhc.2018.10.002.
Treprostinil improves function for complex PAH patients
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Treprostinil is a safe and effective nonsurgical treatment option for severe CTEPH patients.
Major finding: After 24 weeks, 6-minute walk distance improved by 44.98 m from baseline in the high-dose group compared with an increase of 4.29 m from baseline in the low-dose group.
Study details: The data come from a randomized trial of 105 adults with confirmed CTEPH.
Disclosures: The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
Source: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
A prescription for ‘deprescribing’: A case report
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
In 2016, Swapnil Gupta, MD, and John Daniel Cahill, MD, PhD, challenged the field of psychiatry to reexamine our prescribing patterns. They warned against our use of polypharmacy when not attached to improvement in functioning for our patients.1 They were concerned about the lack of evidence for those treatment regimens and for our diagnostic criteria. In their inspiring article, they described how psychiatrists might proceed in the process of “deprescribing” – which they define as a process of pharmacologic regimen optimization through reducing or ending medications for which “benefits no longer outweigh risks.”1
In my practice, I routinely confront medication regimens that I have never encountered in the literature. The evidence for two psychotropics is limited but certainly available, in particular adjunct treatment of antidepressants2 and mood stabilizers.3 The evidence supporting the use of more than two psychotropics, however, is quite sparse. Yet, patients often enter my office on more than five psychotropics. I am also confronted with poorly defined diagnostic labels – which present more as means to justify polypharmacy than a thorough review of the patient’s current state.
Dr. Gupta and Dr. Cahill recommend a series of steps aimed at attempting the deprescription of psychotropics. Those steps include timeliness, knowledge of the patient’s current regimen, discussion about the risk of prescriptions, discussion about deprescribing, choosing the right medications to stop, a plan for describing, and monitoring. In the case presented below, I used some of those steps in an effort to provide the best care for the patient. Key details of the case have been changed, including the name, to protect the patient’s confidentiality.
Overview of the case
Rosalie Bertin is a 54-year-old female who has been treated for depression by a variety of primary care physicians for the better part of the last 30 years. She had tried an array of antidepressants, including sertraline, citalopram, duloxetine, and mirtazapine, over that time. Each seemed to provide some benefit when reviewing the notes, but there is no mention of why she was continued on those medications despite the absence of continuing symptoms. Occasionally, Rosalie would present to her clinician tearful and endorsing sadness, though the record did not comment on reports of energy, concentration, sleep, appetite, and interest.
In 2014, Rosalie’s husband passed away from lung cancer. His death was fairly quick, and initially, Rosalie did not mention any significant emotional complaints. However, when visiting her primary care physician 4 months later, she was noted to experience auditory hallucinations. “Sometimes I hear my husband when I am alone in my home,” she said. Rosalie was referred to a psychiatrist with a diagnosis of “psychosis not otherwise specified.”
When discussing her condition with the psychiatrist, Rosalie mentioned experiencing low mood, and having diminished interest in engaging in activities. “I miss Marc when I go places; I used to do everything with him.” She reported hearing him often but only when at her home. He would say things like, “I miss you,” or ask her about her day. She was diagnosed with “major depressive disorder with psychotic features.” Risperidone was added to the escitalopram, buspirone, and gabapentin that had been started by her primary care physician.
After several months of psychotropic management, the dose of risperidone was titrated to 8 mg per day. Her mood symptoms were unchanged, but she now was complaining of poor concentration and memory. The psychiatrist performed a Mini-Mental State Examination (MMSE). It was noted that taking the MMSE engendered significant anxiety for the patient. Rosalie received a score suggesting mild cognitive impairment. She was started on donepezil for the memory complaint, quetiapine for the continued voices, and recommended for disability.
Once on short-term disability, the patient relocated to live closer to her mother in San Diego and subsequently contacted me about continuing psychiatric care.
Initial visit
Rosalie is a petite white woman, raised in the Midwest, who married her high school sweetheart, and subsequently became an administrative assistant. Rosalie and Marc were unable to have children. Marc was an engineer, and a longtime smoker. She describes their lives as simple – “few friends, few vacations, few problems, few regrets.” She states she misses her husband and often cries when thinking about him.
When asked about psychiatric diagnoses, she answered: “I have psychosis. … My doctor said maybe schizophrenia, but he is not sure yet.” She described schizophrenia as hearing voices. Rosalie also mentioned having memory problems: “They cannot tell if it is Alzheimer’s disease until I die and they look at my brain, but the medication should delay the progression.”
She reported no significant effect from her prior antidepressant trials: “I am not sure if or how they helped.” Rosalie could not explain the role of the medication. “I take medications as prescribed by my doctor,” she said.
When discussing her antipsychotics, she mentioned: “Those are strong medications; it is hard for me to stay awake with them.” She declared having had no changes in the voices while on the risperidone but said they went away since also being on the quetiapine: “I wonder if the combination of the two really fixed my brain imbalance.”
Assessment
I admit that I have a critical bias against the overuse of psychotropics, and this might have painted how I interpreted Rosalie’s story. Nonetheless, I was honest with her and told her of my concerns. I informed her that her diagnosis was not consistent with my understanding of mood and thought disorders. Her initial reports of depression neither met the DSM criteria for depression nor felt consistent with my conceptualization of the illness. She had retained appropriate functioning and seemed to be responding with the sadness expected when facing difficult challenges like grief.
Her subsequent reports of auditory hallucinations were not associated with delusions or forms of disorganization that I would expect in someone with a thought disorder. Furthermore, the context of the onset gave me the impression that this was part of her process of grief. Her poor result in the dementia screen was most surprising and inconsistent with my evaluation. I told her that I suspected that she was not suffering from Alzheimer’s but from being overmedicated and from anxiety at the time of the testing.
She was excited and hesitant about my report. She was surprised by the length of our visit and interested in hearing more from me. Strangely, I wished she had challenged my different approach. I think that I was hoping she would question my conceptualization, the way I hoped she would have done with her prior clinicians. Nonetheless, she agreed to make a plan with me.
Treatment plan
We decided to review each of her medications and discuss their benefits and risks over a couple of visits. She was most eager to discontinue the donepezil, which had caused diarrhea. She was concerned when I informed her of the potential side effects of antipsychotics. “My doctor asked me if I had any side effects at each visit; I answered that I felt nothing wrong; I had not realized that side effects could appear later.”
She was adamant about staying on buspirone, as she felt it helped her the most with her anxiety at social events. She voiced concern about discontinuing the antipsychotics despite being unsettled by my review of their risks. She asked that we taper them slowly.
In regard to receiving psychosocial support throughout this period of deprescribing, Rosalie declined weekly psychotherapy. She reported having a good social network in San Diego that she wanted to rely on.
Outcome
I often worry about consequences of stopping a medication, especially when I was not present at the time of its initiation. I agonize that the patient might relapse from my need to carry out my agenda on deprescribing. I try to remind myself that the evidence supports my decision making. The risks of psychotropics often are slow to show up, making the benefit of deprescribing less tangible. However, this case was straightforward.
Rosalie quickly improved. Tapering the antipsychotics was astonishing to her: “I can think clearly again.” Within 6 months, she was on buspirone only – though willing to discuss its discontinuation. She had a lead for a job and was hoping to return to work soon. Rosalie continued to miss her husband but had not heard him in some time. She has not had symptoms of psychosis or depression. Her cognition and mood were intact on my clinical assessment.
Discussion
Sadly and shockingly, cases like that of Rosalie are common. In my practice, I routinely see patients on multiple psychotropics – often on more than one antipsychotic. Their diagnoses are vague and dubious, and include diagnoses such as “unspecified psychosis” and “cognitive impairments.” Clinicians occasionally worry about relapse and promote a narrative that treatment must be not only long term but lifelong.4 There is some evidence for this perspective in a research context, but the clinical world also is filled with patients like Rosalie.
Her reports of auditory hallucinations were better explained by her grief than by a psychotic process.5 Her memory complaints were better explained by anxiety at the time of her testing while suffering from the side effects from her numerous psychotropics.6 Her depressive complaints were better explained by appropriate sadness in response to stressors. Several months later with fewer diagnoses and far fewer psychotropics, she is functioning better.
Take-home points
- Polypharmacy can lead to psychiatric symptoms and functional impairment.
- Patients often are unaware of the complete risks of psychotropics.
- Psychiatric symptoms are not always associated with a psychiatric disorder.
- Deprescribing can be performed safely and effectively.
- Deprescribing can be performed with the patient’s informed consent and agreement.
References
1. Psychiatr Serv. 2016 Aug 1;67(8):904-7.
2. Focus. 2016 Apr 13; doi: 10.1176/appi.focus.20150041.
3. Bipolar Disord. 2016 Dec;18(8):684-91.
4. Am J Psychiatry. 2017 Sep 1;174(9):840-9.
5. World Psychiatry. 2009 Jun;8(2):67-74.
6. Hosp Community Psychiatry. 1983 Sep;34(9):830-5.
Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Among his writings is chapter 7 in the new book “Critical Psychiatry: Controversies and Clinical Implications” (Springer, 2019).
*This column was updated 1/11/2019.
Dealing with difficult people
Dealing with difficult people is not a new problem. As long as there are at least two people, the potential for conflict will arise. Unfortunately, the workplace or hospital is not immune from tragedies that are born out of poor conflict resolution. Before we go further, please do not ignore the fact that more than 1 million workers are assaulted each year, and more than 60% of Americans are aware of some type of abusive conduct occurring on the job.
Who are those difficult people we may encounter? Anyone and everyone. Difficult people may include our significant others, family members, supervisors, department chairs, colleagues, competitors, trainees, patients and their families, and ancillary personnel. Looking at this list, it is amazing that we aren’t either stymied by never-ending conflict resolution seminars, or rendered completely ineffective in all aspects of life. Daily conflicts can vary in intensity and degree. At one end one can be disgruntled at the person who secured the last doughnut in the break room, and at the other extreme end one is committed to moving forward with a multimillion dollar lawsuit against the company.
Conflicts arise because of a multiplicity of reasons – work style differences, background differences, attitude difference, personality types, and competitive versus cooperative differences. To be effective, each of us must realize that we are more alike than different, and it is our differences that should fuel our passion for providing excellent patient care and customer service.
In particular, be aware of things that can accelerate the potential for conflicts – performance ratings, evaluations, recommendation for promotion, absence of role models or mentors, lack of support amongst colleagues, and failures on the part of leadership to keep promises, appreciate people, maintain personal integrity, or take responsibility for their own errors.
When conflict arises – deal with it! Identify the problem, and if it is legitimate address it as soon as possible. Always remember to document the details in writing; never forget the old adage most of us learned during training: “If it’s not written/documented it wasn’t done or didn’t happen.” More than likely you won’t need to retrieve your written documents concerning a particular conflict, but if the conflict escalates, this type of documentation will prove invaluable.
Communicate with the person or persons with whom you have the conflict – it is essential that you have the “difficult” conversation. This conversation must be done face-to-face and in private. Never communicate by email, social media, or through gossip. Remain calm, professional, and show respect even if the other person does not. At this meeting detail the problem, but also come prepared with suggestions as to how the conflict might be resolved.
Take responsibility – you can’t control situations or people – but you can choose how you will respond to every situation. This is the appropriate time to establish boundaries; avoid any behavior that might be considered bullying or harassment. Redirect negativity that emanates from the person with whom you have the conflict as well as any potentially self-imposed negativity. Make every effort to avoid statements that include “you never” and “you always,” as there are very few absolutes in life. Consider the other person’s perspective as well; try to see it from their point of view because your “personal truth” is not the only “truth.” Our individual personal life experiences form the foundation for much of our opinions and views; therefore, it should be obvious that persons from widely varied backgrounds and cultures will differ in their approaches. If at all possible, give the person another chance; even the most difficult person has good attributes.
Once you have had the “difficult” conversation and there is still no resolution in sight you should take it to management. Everyone has a boss – even the Boss! There is much to gain from involving an impartial party or mediator. This impartial individual is able to understand the viewpoint of all parties involved and frequently that person’s solution may be considered acceptable because it is coming from someone not directly affected by the conflict.
Unresolved conflicts result in many negative effects – interference with one’s career is foremost – and that alone can be a source of undue stress. Other negative effects are the development of a hostile work environment, diminished productivity, low morale, and high employee turnover. Physicians in particular are prone to experiencing an increase in medical errors, litigation claims, and poor patient care when there are unresolved conflicts on the table.
In an ideal world, there are no difficult people; there are either no conflicts or all conflicts are resolved immediately without any lasting deleterious effects. Unfortunately, the world abounds in conflict at varying stages of resolution. As a final bit of advice, in dealing with difficult persons, do not allow conflicts to obscure your goals for successful patient care and/or customer service. Focus on why you decided to join your place of employment and realize that everyone has a role in making the team work! If you are dedicated to addressing conflicts as they arise, and utilizing the strategies outlined, you will often find that foes can truly become friends.
Dr. Cole is associate section chief, gastroenterology, and chief, GI endoscopy, Michael E. DeBakey VA Medical Center; and associate professor, internal medicine, Baylor College of Medicine, Houston.
Dealing with difficult people is not a new problem. As long as there are at least two people, the potential for conflict will arise. Unfortunately, the workplace or hospital is not immune from tragedies that are born out of poor conflict resolution. Before we go further, please do not ignore the fact that more than 1 million workers are assaulted each year, and more than 60% of Americans are aware of some type of abusive conduct occurring on the job.
Who are those difficult people we may encounter? Anyone and everyone. Difficult people may include our significant others, family members, supervisors, department chairs, colleagues, competitors, trainees, patients and their families, and ancillary personnel. Looking at this list, it is amazing that we aren’t either stymied by never-ending conflict resolution seminars, or rendered completely ineffective in all aspects of life. Daily conflicts can vary in intensity and degree. At one end one can be disgruntled at the person who secured the last doughnut in the break room, and at the other extreme end one is committed to moving forward with a multimillion dollar lawsuit against the company.
Conflicts arise because of a multiplicity of reasons – work style differences, background differences, attitude difference, personality types, and competitive versus cooperative differences. To be effective, each of us must realize that we are more alike than different, and it is our differences that should fuel our passion for providing excellent patient care and customer service.
In particular, be aware of things that can accelerate the potential for conflicts – performance ratings, evaluations, recommendation for promotion, absence of role models or mentors, lack of support amongst colleagues, and failures on the part of leadership to keep promises, appreciate people, maintain personal integrity, or take responsibility for their own errors.
When conflict arises – deal with it! Identify the problem, and if it is legitimate address it as soon as possible. Always remember to document the details in writing; never forget the old adage most of us learned during training: “If it’s not written/documented it wasn’t done or didn’t happen.” More than likely you won’t need to retrieve your written documents concerning a particular conflict, but if the conflict escalates, this type of documentation will prove invaluable.
Communicate with the person or persons with whom you have the conflict – it is essential that you have the “difficult” conversation. This conversation must be done face-to-face and in private. Never communicate by email, social media, or through gossip. Remain calm, professional, and show respect even if the other person does not. At this meeting detail the problem, but also come prepared with suggestions as to how the conflict might be resolved.
Take responsibility – you can’t control situations or people – but you can choose how you will respond to every situation. This is the appropriate time to establish boundaries; avoid any behavior that might be considered bullying or harassment. Redirect negativity that emanates from the person with whom you have the conflict as well as any potentially self-imposed negativity. Make every effort to avoid statements that include “you never” and “you always,” as there are very few absolutes in life. Consider the other person’s perspective as well; try to see it from their point of view because your “personal truth” is not the only “truth.” Our individual personal life experiences form the foundation for much of our opinions and views; therefore, it should be obvious that persons from widely varied backgrounds and cultures will differ in their approaches. If at all possible, give the person another chance; even the most difficult person has good attributes.
Once you have had the “difficult” conversation and there is still no resolution in sight you should take it to management. Everyone has a boss – even the Boss! There is much to gain from involving an impartial party or mediator. This impartial individual is able to understand the viewpoint of all parties involved and frequently that person’s solution may be considered acceptable because it is coming from someone not directly affected by the conflict.
Unresolved conflicts result in many negative effects – interference with one’s career is foremost – and that alone can be a source of undue stress. Other negative effects are the development of a hostile work environment, diminished productivity, low morale, and high employee turnover. Physicians in particular are prone to experiencing an increase in medical errors, litigation claims, and poor patient care when there are unresolved conflicts on the table.
In an ideal world, there are no difficult people; there are either no conflicts or all conflicts are resolved immediately without any lasting deleterious effects. Unfortunately, the world abounds in conflict at varying stages of resolution. As a final bit of advice, in dealing with difficult persons, do not allow conflicts to obscure your goals for successful patient care and/or customer service. Focus on why you decided to join your place of employment and realize that everyone has a role in making the team work! If you are dedicated to addressing conflicts as they arise, and utilizing the strategies outlined, you will often find that foes can truly become friends.
Dr. Cole is associate section chief, gastroenterology, and chief, GI endoscopy, Michael E. DeBakey VA Medical Center; and associate professor, internal medicine, Baylor College of Medicine, Houston.
Dealing with difficult people is not a new problem. As long as there are at least two people, the potential for conflict will arise. Unfortunately, the workplace or hospital is not immune from tragedies that are born out of poor conflict resolution. Before we go further, please do not ignore the fact that more than 1 million workers are assaulted each year, and more than 60% of Americans are aware of some type of abusive conduct occurring on the job.
Who are those difficult people we may encounter? Anyone and everyone. Difficult people may include our significant others, family members, supervisors, department chairs, colleagues, competitors, trainees, patients and their families, and ancillary personnel. Looking at this list, it is amazing that we aren’t either stymied by never-ending conflict resolution seminars, or rendered completely ineffective in all aspects of life. Daily conflicts can vary in intensity and degree. At one end one can be disgruntled at the person who secured the last doughnut in the break room, and at the other extreme end one is committed to moving forward with a multimillion dollar lawsuit against the company.
Conflicts arise because of a multiplicity of reasons – work style differences, background differences, attitude difference, personality types, and competitive versus cooperative differences. To be effective, each of us must realize that we are more alike than different, and it is our differences that should fuel our passion for providing excellent patient care and customer service.
In particular, be aware of things that can accelerate the potential for conflicts – performance ratings, evaluations, recommendation for promotion, absence of role models or mentors, lack of support amongst colleagues, and failures on the part of leadership to keep promises, appreciate people, maintain personal integrity, or take responsibility for their own errors.
When conflict arises – deal with it! Identify the problem, and if it is legitimate address it as soon as possible. Always remember to document the details in writing; never forget the old adage most of us learned during training: “If it’s not written/documented it wasn’t done or didn’t happen.” More than likely you won’t need to retrieve your written documents concerning a particular conflict, but if the conflict escalates, this type of documentation will prove invaluable.
Communicate with the person or persons with whom you have the conflict – it is essential that you have the “difficult” conversation. This conversation must be done face-to-face and in private. Never communicate by email, social media, or through gossip. Remain calm, professional, and show respect even if the other person does not. At this meeting detail the problem, but also come prepared with suggestions as to how the conflict might be resolved.
Take responsibility – you can’t control situations or people – but you can choose how you will respond to every situation. This is the appropriate time to establish boundaries; avoid any behavior that might be considered bullying or harassment. Redirect negativity that emanates from the person with whom you have the conflict as well as any potentially self-imposed negativity. Make every effort to avoid statements that include “you never” and “you always,” as there are very few absolutes in life. Consider the other person’s perspective as well; try to see it from their point of view because your “personal truth” is not the only “truth.” Our individual personal life experiences form the foundation for much of our opinions and views; therefore, it should be obvious that persons from widely varied backgrounds and cultures will differ in their approaches. If at all possible, give the person another chance; even the most difficult person has good attributes.
Once you have had the “difficult” conversation and there is still no resolution in sight you should take it to management. Everyone has a boss – even the Boss! There is much to gain from involving an impartial party or mediator. This impartial individual is able to understand the viewpoint of all parties involved and frequently that person’s solution may be considered acceptable because it is coming from someone not directly affected by the conflict.
Unresolved conflicts result in many negative effects – interference with one’s career is foremost – and that alone can be a source of undue stress. Other negative effects are the development of a hostile work environment, diminished productivity, low morale, and high employee turnover. Physicians in particular are prone to experiencing an increase in medical errors, litigation claims, and poor patient care when there are unresolved conflicts on the table.
In an ideal world, there are no difficult people; there are either no conflicts or all conflicts are resolved immediately without any lasting deleterious effects. Unfortunately, the world abounds in conflict at varying stages of resolution. As a final bit of advice, in dealing with difficult persons, do not allow conflicts to obscure your goals for successful patient care and/or customer service. Focus on why you decided to join your place of employment and realize that everyone has a role in making the team work! If you are dedicated to addressing conflicts as they arise, and utilizing the strategies outlined, you will often find that foes can truly become friends.
Dr. Cole is associate section chief, gastroenterology, and chief, GI endoscopy, Michael E. DeBakey VA Medical Center; and associate professor, internal medicine, Baylor College of Medicine, Houston.
Glucocorticoid Treatment of Symptomatic Sarcoidosis in 2 Morbidly Obese Patients
Corticosteroid management for patients with sarcoidosis requires the need for close monitoring to detect and manage any complications that may arise during treatment.
Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.1
Diagnosis
A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.
Symptoms
Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.2 Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.2 Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).3
Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.1 Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.2-4
Sarcoidosis in Obese Patients
Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.8 Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.9 As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.
Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.10,11 Higher doses are suggested for involvement of other organs, such as the heart.2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.13 No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.
Case 1: Pulmonary Sarcoidosis
A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).
The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.
Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.
Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.
Case 2: Cardiac Sarcoidosis
A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H2O while sleeping.
On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO2 blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.
The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.
Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.
One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA1c) of 6.4%. He began treatment with glipizide 5 mg daily.
After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.
Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.
Discussion
These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.
Sarcoidosis/Obesity Relationship
Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.5-7 Although the mechanism of association is unclear, several possibilities have been proposed.
Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.14 This was investigated in one of our patients.
Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.15 Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.15 Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.16 These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.15
Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.5
Management of Comorbid Sarcoidosis and Obesity
Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.18
For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.19 In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.20
Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.27 Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.28-30
Our Prescription Model
We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.
Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.
Conclusion
Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.
We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.
Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.
1. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-2165.
2. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Sarcoidosis. Lancet. 2014;383 (9923):1155-1167.
3. Lal C, Medarov BI, Judson MA. Interrelationship between sleep-disordered breathing and sarcoidosis. Chest. 2015;148(4):1105-1114.
4. Dobarro D, Schreiber BE, Handler C, Beynon H, Denton CP, Coghlan JG. Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data. Am J Cardiol. 2013;111(2):278-285.
5. Cozier YC, Coogan PF, Govender P, Berman JS, Palmer JR, Rosenberg L. Obesity and weight gain in relation to incidence of sarcoidosis in US black women: data from the Black Women’s Health Study. Chest. 2015;147(4):1086-1093.
6. Harpsoe MC, Basit S, Andersson M, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014;43(3):843-855.
7. Ungprasert P, Crowson CS, Matteson EL. Smoking, obesity and risk of sarcoidosis: a population-based nested case-control study. Respir Med. 2016;120:87-90.
8. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889-891.
9. Nelson KM. The burden of obesity among a national probability sample of veterans. J Gen Intern Med. 2006; 21(9):915-919.
10. Moller DR, Chen ES. Systemic sarcoidosis. In: Grippi MA, Elias JA, Fishman et al, eds. Fishman’s Pulmonary Diseases and Disorders. 5th ed. New York, NY: McGraw-Hill; 2015: 823-841
11. Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:1188-1206.
12. Patel D, Hamzeh NY. Immunosuppressive management of cardiac sarcoidosis. In: Freeman AM, Weinberger HD, eds. Cardiac Sarcoidosis. New York, NY: Springer; 2015:103-112.
13. Abdullah A, Peeters A, de Courten M, Stoelwinder J. The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies. Diabetes Res Clin Pract. 2010;89(3):309-319.
14. Anthony J, Esper GJ, Ioachimescu A. Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary. 2016;19(1):19-29.
15. Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol. 2012;13(8):707-712.
16. Matarese G, Leiter EH, La Cava A. Leptin in autoimmunity: many questions, some answers. Tissue Antigens. 2007;70(2):87-95.
17. Doughan AR, Williams BR. Cardiac sarcoidosis. Heart. 2006;92(2):282-288.
18. Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol. 2001;88(9):1006-1010.
19. Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clin Pharmacol Ther. 1984;36(6):824-831.
20. Dunn TE, Ludwig EA, Slaughter RL, Camara DS, Jusko WJ. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther. 1991;49(5):536-549.
21. Eastwood PR, Malhotra A, Palmer LJ, et al. Obstructive sleep apnoea: from pathogenesis to treatment: current controversies and future directions. Respirology. 2010;15(4):587-595.
22. Wong HS, Williams AJ, Mok Y. The relationship between pulmonary hypertension and obstructive sleep apnea. Curr Opin Pulm Med. 2017;23(6):517-521.
23. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009;373(9657):82-93.
24. Handa T, Nagai S, Miki S, et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246-1252.
25. Baughman RP, Engel PJ, Taylor L, Lower EE. Survival in sarcoidosis-associated pulmonary hypertension: the importance of hemodynamic evaluation. Chest. 2010;138(5):1078-1085.
26. Birnie DH, Kandolin R, Nery PB, Kupari M. Cardiac manifestations of sarcoidosis: diagnosis and management. Eur Heart J. 2017;38(35):2663-2670.
27. Nunes H, Humbert M, Capron F, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006;61(1):68-74.
28. Judson MA, Highland KB, Kwon S, et al. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(2):139-145.
29. Baughman RP, Culver DA, Cordova FC, et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014;145(4):810-817.
30. Baughman RP, Judson MA, Lower EE, et al. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):110-120.
Corticosteroid management for patients with sarcoidosis requires the need for close monitoring to detect and manage any complications that may arise during treatment.
Corticosteroid management for patients with sarcoidosis requires the need for close monitoring to detect and manage any complications that may arise during treatment.
Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.1
Diagnosis
A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.
Symptoms
Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.2 Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.2 Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).3
Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.1 Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.2-4
Sarcoidosis in Obese Patients
Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.8 Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.9 As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.
Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.10,11 Higher doses are suggested for involvement of other organs, such as the heart.2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.13 No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.
Case 1: Pulmonary Sarcoidosis
A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).
The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.
Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.
Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.
Case 2: Cardiac Sarcoidosis
A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H2O while sleeping.
On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO2 blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.
The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.
Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.
One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA1c) of 6.4%. He began treatment with glipizide 5 mg daily.
After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.
Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.
Discussion
These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.
Sarcoidosis/Obesity Relationship
Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.5-7 Although the mechanism of association is unclear, several possibilities have been proposed.
Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.14 This was investigated in one of our patients.
Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.15 Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.15 Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.16 These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.15
Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.5
Management of Comorbid Sarcoidosis and Obesity
Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.18
For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.19 In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.20
Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.27 Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.28-30
Our Prescription Model
We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.
Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.
Conclusion
Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.
We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.
Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.
Sarcoidosis is a systemic inflammatory condition with pulmonary and extrapulmonary manifestations. The etiology of sarcoidosis remains unknown. Iannuzzi and colleagues hypothesize that an unknown antigen sets off a cycle of chronic granulomatous inflammation in a genetically susceptible host.1
Diagnosis
A diagnosis of sarcoidosis is typically based on a patient having an appropriate clinical presentation and a biopsy, often of lungs or skin, showing noncaseating granulomas.
Symptoms
Of the protean manifestations of sarcoidosis, respiratory symptoms are the most common and typically include subacute or chronic cough and progressive dyspnea on exertion.2 Chest imaging may show only hilar or mediastinal lymphadenopathy, diffuse micronodular lung disease, or signs of chronic inflammation and fibrosis.2 Upper airway involvement and progressive lung disease may lead to increased risk of sleep-disordered breathing, particularly obstructive sleep apnea (OSA).3
Sarcoidosis also can develop in the skin, neurologic system, heart, and other systems. It typically presents as areas of patchy, infiltrative inflammation. In the heart, this can lead to heart failure, often with reduced ejection fraction (EF) and ventricular arrhythmias.1 Pulmonary hypertension (PH) may result from multiple possible mechanisms, including left-heart disease, parenchymal lung disease, sleep-disordered breathing, and possibly direct inflammation and compression of the pulmonary vasculature.2-4
Sarcoidosis in Obese Patients
Emerging evidence shows that sarcoidosis occurs at higher rates in obese patients, suggesting that obesity may be a risk factor for the disease.5-7 Rates of morbid obesity are increasing in the US. From 2000 to 2010, the prevalence of morbid obesity, defined as body mass index (BMI) > 40, increased by 70%, with even larger relative increases in the number of patients with BMI > 50.8 Among veterans who receive health care at the US Department of Veterans Affairs (VA) medical centers, 28% are obese.9 As a result, VA physicians will encounter more patients with morbid obesity and another significant comorbid condition.
Managing symptomatic sarcoidosis in patients with morbid obesity poses a dilemma. Typical treatment for symptomatic pulmonary sarcoidosis is prednisone 20 mg to 40 mg daily.10,11 Higher doses are suggested for involvement of other organs, such as the heart.2,12 Associated weight gain from corticosteroid treatment with possible sleep-disordered breathing increases an already high risk of metabolic complications in morbidly obese patients.13 No clear consensus exists on how corticosteroid doses should be adjusted. We present 2 cases that highlight the complexity of corticosteroid management in the obese sarcoidosis patient.
Case 1: Pulmonary Sarcoidosis
A 43-year-old morbidly obese man presented to his primary care provider with subacute onset of dyspnea. He had a history of OSA that was diagnosed empirically at another institution without polysomnogram and treated with autotitrating continuous positive airway pressure (CPAP).
The patient was admitted for expedited evaluation. His BMI was 63.2 with declining exercise tolerance and hypoxemia on ambulation. His oxyhemoglobin saturation rate was 85% after walking a short distance. Ongoing CPAP therapy for sleep-disordered breathing made laboratory evaluation for obesity hypoventilation syndrome (OHS) challenging. The patient’s serum bicarbonate test result was normal. Serum markers as well as induced sputum stains and cultures were negative for evidence of mycobacterial or fungal infections. A chest radiograph showed bilateral hilar adenopathy and miliary nodularity. Pulmonary function testing revealed severe obstruction and restriction as well as a moderate diffusion impairment. Bronchoscopy with biopsy revealed noncaseating granulomas consistent with sarcoidosis. An electrocardiogram (ECG) was normal. Transthoracic echocardiogram showed evidence of diastolic dysfunction and a mildly dilated right ventricle with normal function, suggestive of possible PH. We were unable to assess his pulmonary artery pressure.
Upon release, the patient began a course of 50 mg (0.24 mg/kg actual body weight) oral prednisone daily and home oxygen.
Six weeks after initiation of steroids, the patient reported that his dyspnea had improved. However, after 6 months of steroid treatment, his weight increased from 462 pounds to 503 pounds. He was evaluated for possible neurosarcoidosis with hypothalamic or pituitary involvement as a possible cause for the weight gain. Brain magnetic resonance imaging and hormonal testing were normal. We considered starting him on a steroid-sparing agent. However, after early efficacy, prednisone was gradually tapered and, after 1 year of treatment, discontinued. At that time, symptoms had substantially improved: His pulmonary function tests had normalized, and he was weaned off oxygen; repeat chest imaging showed only residual enlargement of the hilar lymph nodes. After cessation of steroids, the patient was able to lose 20 pounds.
Case 2: Cardiac Sarcoidosis
A 57-year-old morbidly obese man presented to the emergency department with subacute increasing dyspnea on exertion. He had a known history of sarcoidosis diagnosed by skin biopsy 28 years earlier but had been without treatment for decades. His history also included prediabetes, heart failure with preserved ejection fraction (HFpEF), OSA with an apnea hypopnea index (AHI) of 114.7 per hour, PH diagnosed by prior echocardiogram, and paroxysmal atrial fibrillation (AF). He required 2 L/m home oxygen and bilevel positive airway pressure (PAP) of 22/17 cm H2O while sleeping.
On physical examination, the patient’s BMI was 54.6. He was tachycardic and hypoxemic on his usual oxygen flow rate. His serum bicarbonate, arterial blood pH, and PaCO2 blood levels were normal. We heard bibasilar crackles over the lungs. Chest radiograph revealed an enlarged cardiac silhouette and bilateral infiltrates concerning for cardiogenic pulmonary edema. An echocardiogram showed a restrictive filling pattern with preserved EF and moderate dilation and dysfunction of the right ventricle, consistent with PH. A positron emission tomography (PET)/computed tomography scan, the preferred study for cardiac sarcoidosis, suggested active infiltrative septal cardiac disease and active hilar and mediastinal adenopathy. This was concerning for both cardiac and pulmonary sarcoidosis. Ongoing treatment of sleep-disordered breathing made laboratory assessment for OHS challenging. Given his intact EF, the absence of ventricular arrhythmias, and improvement with diuretics and bilevel PAP, specific treatment of sarcoidosis was not initiated. He was discharged home with a plan to re-evaluate sarcoidosis symptoms and initiate treatment as an outpatient.
The patient was readmitted 2 weeks later with worsened dyspnea, hypoxemia, and volume overload. A right heart catheterization confirmed PH with a mean pulmonary artery pressure of 44 mm Hg (68/32 mm Hg) and pulmonary vascular resistance of 4.6 Wood units. We also found evidence of left-heart dysfunction with a pulmonary capillary wedge pressure of 16 mm Hg.
Given his recurrent symptoms, evidence of active myocardial inflammation on recent PET, and prior biopsy-proven sarcoidosis, we made the decision to pursue treatment for symptomatic sarcoidosis. He began a course of 40 mg (0.20 mg/kg actual body weight) oral prednisone daily. He now required 6 L/m supplemental oxygen. After IV diuretic therapy during his hospitalization, the patient was discharged on his preadmission oral diuretic dose. Pulmonary vasodilator therapy was not initiated for PH as left heart disease and sleep-disordered breathing needed to be managed first.
One month after steroid initiation, the patient reported that the dyspnea and hypoxemia had markedly improved. His oxygen flow rate was reduced to 2 L/m. He remained normotensive and had no further difficulties with fluid retention or volume overload on a stable dose of oral diuretics. He had elevated blood glucose with a glycated hemoglobin (HbA1c) of 6.4%. He began treatment with glipizide 5 mg daily.
After 3 months, he returned to the emergency department with hyperosmolar nonketotic hyperglycemia due to steroid-induced diabetes mellitus (DM). His HbA1c was now 17.1%. The patient was started on a home insulin regimen, and his blood sugar values subsequently improved. He remained symptomatically better and lost 40 pounds with a guided weight management program and a stable diuretic regimen. He underwent arrhythmia evaluation with a Holter monitor that showed AF without ventricular arrhythmias.
Unfortunately, he did not return for cardiac or pulmonary reevaluation, and was lost to follow-up. Nine months after initiation of treatment, the patient died after an out-of-hospital cardiac arrest.
Discussion
These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.
Sarcoidosis/Obesity Relationship
Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.5-7 Although the mechanism of association is unclear, several possibilities have been proposed.
Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.14 This was investigated in one of our patients.
Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.15 Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.15 Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.16 These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.15
Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.5
Management of Comorbid Sarcoidosis and Obesity
Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.18
For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.19 In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.20
Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.27 Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.28-30
Our Prescription Model
We empirically prescribed moderate total doses of prednisone—although low on a mg/kg basis—to balance efficacy and the risk of adverse effects in these 2 morbidly obese patients. We also managed treatment-related complications with guided weight-management programs, CPAP, or noninvasive ventilation for sleep-disordered breathing, and DM treatment.
Our cases demonstrate the need for close monitoring of weight, blood pressure, and blood glucose to detect and treat any complications that may arise during corticosteroid treatment. Aggressive treatment of hyperglycemia with insulin or oral alternatives associated with weight loss such as metformin, sulfonylureas, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide 1 receptor agonists, may help prevent further DM complications. Sleep-disordered breathing should be assessed and treated. Bariatric surgery may be an option to treat obesity and minimize resultant complications. In our patients, and likely many others, the degree of respiratory and cardiac disease coupled with poor wound healing due to chronic prednisone, may increase the procedural risks.
Conclusion
Our experiences with these patients illustrate that symptomatic and objective improvement in sarcoidosis may be achieved in morbidly obese patients with doses of prednisone that are generally considered moderate, though quite low on a mg/kg basis.
We believe ours is the first report to describe the use of corticosteroids for the treatment of sarcoidosis in patients with morbid obesity. That 2 patients were treated at a single VA medical center within 1-year likely reflects the rising incidence of morbid obesity in the US veteran population and suggests that other federal practitioners might encounter similar patients.
Further study may show that, as an alternative to initial moderate-dose prednisone, patients with symptomatic sarcoidosis and extreme obesity might be started on antimetabolite or antitumor necrosis factor medication or on low-dose prednisone and a second steroid-sparing agent.
1. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-2165.
2. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Sarcoidosis. Lancet. 2014;383 (9923):1155-1167.
3. Lal C, Medarov BI, Judson MA. Interrelationship between sleep-disordered breathing and sarcoidosis. Chest. 2015;148(4):1105-1114.
4. Dobarro D, Schreiber BE, Handler C, Beynon H, Denton CP, Coghlan JG. Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data. Am J Cardiol. 2013;111(2):278-285.
5. Cozier YC, Coogan PF, Govender P, Berman JS, Palmer JR, Rosenberg L. Obesity and weight gain in relation to incidence of sarcoidosis in US black women: data from the Black Women’s Health Study. Chest. 2015;147(4):1086-1093.
6. Harpsoe MC, Basit S, Andersson M, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014;43(3):843-855.
7. Ungprasert P, Crowson CS, Matteson EL. Smoking, obesity and risk of sarcoidosis: a population-based nested case-control study. Respir Med. 2016;120:87-90.
8. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889-891.
9. Nelson KM. The burden of obesity among a national probability sample of veterans. J Gen Intern Med. 2006; 21(9):915-919.
10. Moller DR, Chen ES. Systemic sarcoidosis. In: Grippi MA, Elias JA, Fishman et al, eds. Fishman’s Pulmonary Diseases and Disorders. 5th ed. New York, NY: McGraw-Hill; 2015: 823-841
11. Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:1188-1206.
12. Patel D, Hamzeh NY. Immunosuppressive management of cardiac sarcoidosis. In: Freeman AM, Weinberger HD, eds. Cardiac Sarcoidosis. New York, NY: Springer; 2015:103-112.
13. Abdullah A, Peeters A, de Courten M, Stoelwinder J. The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies. Diabetes Res Clin Pract. 2010;89(3):309-319.
14. Anthony J, Esper GJ, Ioachimescu A. Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary. 2016;19(1):19-29.
15. Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol. 2012;13(8):707-712.
16. Matarese G, Leiter EH, La Cava A. Leptin in autoimmunity: many questions, some answers. Tissue Antigens. 2007;70(2):87-95.
17. Doughan AR, Williams BR. Cardiac sarcoidosis. Heart. 2006;92(2):282-288.
18. Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol. 2001;88(9):1006-1010.
19. Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clin Pharmacol Ther. 1984;36(6):824-831.
20. Dunn TE, Ludwig EA, Slaughter RL, Camara DS, Jusko WJ. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther. 1991;49(5):536-549.
21. Eastwood PR, Malhotra A, Palmer LJ, et al. Obstructive sleep apnoea: from pathogenesis to treatment: current controversies and future directions. Respirology. 2010;15(4):587-595.
22. Wong HS, Williams AJ, Mok Y. The relationship between pulmonary hypertension and obstructive sleep apnea. Curr Opin Pulm Med. 2017;23(6):517-521.
23. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009;373(9657):82-93.
24. Handa T, Nagai S, Miki S, et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246-1252.
25. Baughman RP, Engel PJ, Taylor L, Lower EE. Survival in sarcoidosis-associated pulmonary hypertension: the importance of hemodynamic evaluation. Chest. 2010;138(5):1078-1085.
26. Birnie DH, Kandolin R, Nery PB, Kupari M. Cardiac manifestations of sarcoidosis: diagnosis and management. Eur Heart J. 2017;38(35):2663-2670.
27. Nunes H, Humbert M, Capron F, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006;61(1):68-74.
28. Judson MA, Highland KB, Kwon S, et al. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(2):139-145.
29. Baughman RP, Culver DA, Cordova FC, et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014;145(4):810-817.
30. Baughman RP, Judson MA, Lower EE, et al. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):110-120.
1. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-2165.
2. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Sarcoidosis. Lancet. 2014;383 (9923):1155-1167.
3. Lal C, Medarov BI, Judson MA. Interrelationship between sleep-disordered breathing and sarcoidosis. Chest. 2015;148(4):1105-1114.
4. Dobarro D, Schreiber BE, Handler C, Beynon H, Denton CP, Coghlan JG. Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data. Am J Cardiol. 2013;111(2):278-285.
5. Cozier YC, Coogan PF, Govender P, Berman JS, Palmer JR, Rosenberg L. Obesity and weight gain in relation to incidence of sarcoidosis in US black women: data from the Black Women’s Health Study. Chest. 2015;147(4):1086-1093.
6. Harpsoe MC, Basit S, Andersson M, et al. Body mass index and risk of autoimmune diseases: a study within the Danish National Birth Cohort. Int J Epidemiol. 2014;43(3):843-855.
7. Ungprasert P, Crowson CS, Matteson EL. Smoking, obesity and risk of sarcoidosis: a population-based nested case-control study. Respir Med. 2016;120:87-90.
8. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889-891.
9. Nelson KM. The burden of obesity among a national probability sample of veterans. J Gen Intern Med. 2006; 21(9):915-919.
10. Moller DR, Chen ES. Systemic sarcoidosis. In: Grippi MA, Elias JA, Fishman et al, eds. Fishman’s Pulmonary Diseases and Disorders. 5th ed. New York, NY: McGraw-Hill; 2015: 823-841
11. Judson MA, Morgenthau AS, Baughman RP. Sarcoidosis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel’s Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:1188-1206.
12. Patel D, Hamzeh NY. Immunosuppressive management of cardiac sarcoidosis. In: Freeman AM, Weinberger HD, eds. Cardiac Sarcoidosis. New York, NY: Springer; 2015:103-112.
13. Abdullah A, Peeters A, de Courten M, Stoelwinder J. The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies. Diabetes Res Clin Pract. 2010;89(3):309-319.
14. Anthony J, Esper GJ, Ioachimescu A. Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review. Pituitary. 2016;19(1):19-29.
15. Kanneganti TD, Dixit VD. Immunological complications of obesity. Nat Immunol. 2012;13(8):707-712.
16. Matarese G, Leiter EH, La Cava A. Leptin in autoimmunity: many questions, some answers. Tissue Antigens. 2007;70(2):87-95.
17. Doughan AR, Williams BR. Cardiac sarcoidosis. Heart. 2006;92(2):282-288.
18. Yazaki Y, Isobe M, Hiroe M, et al. Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol. 2001;88(9):1006-1010.
19. Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clin Pharmacol Ther. 1984;36(6):824-831.
20. Dunn TE, Ludwig EA, Slaughter RL, Camara DS, Jusko WJ. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther. 1991;49(5):536-549.
21. Eastwood PR, Malhotra A, Palmer LJ, et al. Obstructive sleep apnoea: from pathogenesis to treatment: current controversies and future directions. Respirology. 2010;15(4):587-595.
22. Wong HS, Williams AJ, Mok Y. The relationship between pulmonary hypertension and obstructive sleep apnea. Curr Opin Pulm Med. 2017;23(6):517-521.
23. Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009;373(9657):82-93.
24. Handa T, Nagai S, Miki S, et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246-1252.
25. Baughman RP, Engel PJ, Taylor L, Lower EE. Survival in sarcoidosis-associated pulmonary hypertension: the importance of hemodynamic evaluation. Chest. 2010;138(5):1078-1085.
26. Birnie DH, Kandolin R, Nery PB, Kupari M. Cardiac manifestations of sarcoidosis: diagnosis and management. Eur Heart J. 2017;38(35):2663-2670.
27. Nunes H, Humbert M, Capron F, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006;61(1):68-74.
28. Judson MA, Highland KB, Kwon S, et al. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(2):139-145.
29. Baughman RP, Culver DA, Cordova FC, et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014;145(4):810-817.
30. Baughman RP, Judson MA, Lower EE, et al. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):110-120.
New CHEST expert panel advice on cough diagnosis
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
FROM THE JOURNAL CHEST®
Managing the Silent Epidemic of Nonalcoholic Fatty Liver Disease
For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.
Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.
“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.
The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.
The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.
NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.
The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.
Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.
For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.
Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.
“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.
The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.
The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.
NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.
The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.
Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.
For many years, viral hepatitis and particularly hepatitis C have been the bread and butter for clinicians dealing with chronic liver diseases. Over the past few years the Veterans Health Administration (VHA) has been incredibly successful in identifying, treating, and curing a significant proportion of veterans of this viral disease. However, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and will soon overtake hepatitis C virus as the leading cause of liver transplantation. NAFLD covers a disease spectrum ranging from nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis (NASH) to liver cirrhosis and liver cancer or liver failure. In the absence of effective treatment approaches, it is not surprising that NAFLD will create financial challenges for the VHA and US health care budgets. It is thus appropriate that Federal Practitioner has decided to publish a series of articles highlighting NAFLD and how it affects millions of Americans on its way to reaching quietly epidemic proportions within the VHA and across the globe.
Although NAFLD seems to have quietly and quickly reached epidemic proportions, its obscurity should not be surprising. NAFLD does not cause obvious symptoms in most patients, there is no simple test available for diagnosis of NASH, and disease-specific medications have not yet been approved for treatment. Primary care providers (PCPs) are the first point of medical contact for a majority of patients with or at risk for NAFLD; shockingly, NAFLD is greatly underrecognized, resulting in delayed diagnoses, which impact both health-related and quality-of-life outcomes in these patients. As emphasized in “Identifying and Treating Nonalcoholic Fatty Liver Disease” by Hunt and colleagues (page 20), PCPs should focus on 4 main aspects related to NAFLD: (1) Does my patient have NAFL? (2) Is my patient at risk for NASH and its ensuing manifestations? (3) Do simple noninvasive serum liver fibrosis markers suggest presence of clinically relevant liver fibrosis? and (4) Does my patient benefit from being referred to a specialist. The PCP is integral in optimally managing medical comorbidities and metabolic abnormalities as well as coordinating intense lifestyle and exercise interventions.
“Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans” by Shetty and Syn (page 14) discusses the epidemiology and economic burden of NAFLD in the US and how it will affect the health of veterans. Chronic liver disease is a major cause of mortality, morbidity, and health care resource utilization worldwide. Over the past 3 decades, NAFLD has gone from obscure liver diseases to the most common cause of chronic liver disease affecting 25% of the world’s population. Patients with NAFL who have advanced to NASH have an increased risk of liver-specific death. NASH is among the top etiologies for hepatocellular cancer and the fastest growing indication for liver transplantation, projected to overtake hepatitis C virus as the leading cause of liver transplantation. Most disturbing though is the fact that patients with NASH are the least likely to be surveyed for hepatocellular cancer development and the most likely to die while awaiting liver transplantation. Recent modeling estimates a 178% increase in liver deaths related to NASH by 2030.
The clinical burden of all stages of NAFLD is related to its prevalence, incidence, and progressiveness and has to be coupled with its tremendous economic burden based on inpatient, outpatient, professional services, emergency department, and pharmacy costs. It is thus not surprising that we are heading toward a serious health care crisis in the next few decades with the cost of managing NAFLD complications alone approaching an estimated 10-year economic burden of nearly $1 trillion.
The third article by Glass and colleagues (In press) puts the spectrum of NAFLD in the context of a disrupted systemic metabolic environment related to overnutrition alongside reduced physical activity. It is not surprising that type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease are frequent comorbidities present in a high proportion of patients with NAFLD. The prevalence of NAFLD among people with T2DM exceeds 60%. Importantly, convincing evidence has accumulated supporting the concept that interactions between these metabolic syndrome components and NAFLD are complex and bidirectional. Evidence from cross-sectional and longitudinal studies favors the presence of NAFLD and its severity preceding and/or promoting the development of metabolic comorbidities such as T2DM. Concomitantly, the presence of T2DM seems to accelerate the clinical course of NAFLD and is a predictor of advanced liver fibrosis and mortality. Compared with diseases that have a single etiology, such as viral hepatitis, NAFLD is a very complex disease with multiple interacting metabolic pathways that operate in an individual, leading to the clinical manifestation. Clearly, our present understanding of NAFLD/NASH as a single conglomerate disease is overly simplistic, and further study is warranted.
NAFLD and its variations comprise an increasing number and proportion of referral to hepatologists or providers with experience treating patients with chronic liver disease for the management of advanced disease stages; similarly, PCPs face the challenge to manage early stages of NAFLD. Given the magnitude of the problem of NAFLD, it is imperative that dedicated control efforts at the population level must intensify. As is emphasized in the fourth article of this series (In press), Puri and Fuchs call for a replacement of the traditional health care model of office visits with individual specialist working in silos. To overcome the narrow focus of a subspecialty outpatient clinic, time constraints, and gaps in NAFLD awareness, a patient-centered multidisciplinary approach to the treatment and coordination of care for the medically complex NAFLD patients is needed. The VHA is the largest integrated health care system in the US and is well positioned to implement an organizational strategy to facilitate standardized NAFLD care. The proposed model is centered on a broad assessment of the patient, involving the input from several disciplines; on completion of the assessment, a multidisciplinary team will formulate a personalized intervention plan.
The composition of this multidisciplinary team will vary based on expertise and resources available in each clinical setting. Once an intervention has been started, tracking and monitoring of intermediate and long-term functional outcomes will be helpful to modify the intervention in case outcomes are not achieved. Patient education, from the initial assessment until the intervention phase, plays a critical element to ensure that the patient has sufficient knowledge and skills to achieve the treatment goals set with their health care team.
Ultimately, integration of health care services will lead to better quality of care, increased patient satisfaction, and importantly to improved health care service utilization that will reduce health care resources and costs. Although such a proposal may seem ambitious, it is now the time for innovative thinking that will create sustainable solutions for the silent epidemic of NAFLD. Without advancing a proactive vision, the VA and the world will soon become saddled with an unmanageable economic and health care burden.
Identifying and Treating Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (
In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.19
Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.24 When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.25 Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.26
In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.
Screening for Advanced Fibrosis
Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).29 
Does This Patient Have NAFLD?
To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).16 
Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated. 
Evaluation of fasting glucose or hemoglobin A1c (HbA1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.16 Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.39
In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.
Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.16
Encouraging Patients to Pursue Intensive Lifestyle InterventionS
Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.43,44 
In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.46
To start the conversation, the health care provider can explain that
- Why would you want to lose weight and exercise?
- How might you go about it in order to succeed?
- What are the 3 best reasons for you to do it?
- How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
- The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
- So what do you think you will do?
Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.47
This personalized action plan facilitates successful health behavior change.48 Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.49 In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.50 This simple daily measure seems to reinforce a patient’s action plan.
Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.51 For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.52 In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.
Effective VHA interventions
In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).55 In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.55 Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.56 To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.57
To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.58 Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.
In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.26 In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.59 Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.60 The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.63,64
Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.11,67
Conclusion
Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).2 
NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.
Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.3,16,18 Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.68 The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.55 
To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.33,37
In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.
1. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273.
2. Kanwal F, Kramer JR, Duan Z, et al. Trends in the burden of nonalcoholic fatty liver disease in a United States cohort of veterans. Clin Gastroenterol Hepatol. 2016;14(2):301-308.
3. Golabi P, Otgonsuren M, Cable R, et al. Non-alcoholic fatty liver disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL). Health Qual Life Outcomes. 2016;14(1):18.
4. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30(5):1212-1218.
5. Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13(4):511-531.
6. Centers for Disease Control and Prevention. About Prediabetes & Type 2 Diabetes. https://www.cdc.gov/diabetes/prevention/prediabetes-type2/index.html. Updated June 11, 2018. Accessed November 7, 2018.
7. Littman AJ, Jacobson IG, Boyko EJ, Powell TM, Smith TC; Millennium Cohort Study Team. Weight change following US military service. Int J Obes (Lond). 2013;37(2):244-253.
8. Breland JY, Phibbs CS, Hoggatt KJ, et al. The obesity epidemic in the Veterans Health Administration: prevalence among key populations of women and men veterans. J Gen Intern Med. 2017;32(suppl 1):11-17.
9. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854.
10. Bazick J, Donithan M, Neuschwander-Tetri BA, et al. Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care. 2015;38(7):1347-1355.
11. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
12. Bril F, Barb D, Portillo‐Sanchez P, et al. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease. Hepatology. 2017;65(4):1132-1144.
13. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017;377(21):2063-2072.
14. Nasr P, Ignatova S, Kechagias S, Ekstedt M. Natural history of nonalcoholic fatty liver disease: a prospective follow-up study with serial biopsies. Hepatol Commun. 2018;27(2):199-210.
15. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643-654.
16. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402.
17. Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577-1586.
18. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-397.
19. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US Veterans, 2001-2013. Gastroenterology 2015;149(6):1471-1482.
20. Mittal S, El-Serag HB, Sada YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14(1):124-131.
21. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol. 2017;4(1):e000139.
22. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56(1):255-266.
23. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
24. Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.
25. Haw JS, Galaviz KI, Straus AN, et al. Long-term sustainability of diabetes prevention approaches: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2017;177(12):1808-1817.
26. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379-388.
27. Kleiner DE, Brunt EM, Van Natta M, et al; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321.
28. Bedossa P; FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology. 2014;60(2):565-567.
29. Tapper EB, Sengupta N, Hunink MG, Afdhal NH, Lai M. Cost-effective evaluation of nonalcoholic fatty liver disease with NAFLD fibrosis score and vibration controlled transient elastography. Am J Gastroenterol. 2015;110(9):1298-1304.
30. Cui J, Ang B, Haufe W, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non‐invasive diagnosis of advanced fibrosis in biopsy‐proven non‐alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271-1280.
31. Tapper EB, Lok AS-F. Use of liver imaging and biopsy in clinical practice. N Engl J Med . 2017;377(8):756-768.
32. Sterling RK, Lissen E, Clumeck N; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-1325.
33. Imler T. Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/fibrosis-4-score. Published 2018. Accessed November 7, 2018.
34. Sun W, Cui H , Li N, et al. Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: a meta-analysis study. Hepatol Res. 2016;46(9):862-870.
35. Imler T, Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/nafld-fibrosis-score. Published 2018. Accessed November 7, 2018.
36. Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441-1447.
37. Patel YA, Gifford EJ, Glass LM, et al. Identifying non-alcoholic fatty liver disease advanced fibrosis in the Veterans Health Administration. Dig Dis Sci. 2018;63(9): 2259-2266.
38. Armstrong MJ, Houlihan DD, Bentham L, et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J Hepatol. 2012;56(1):234-240.
39. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413-1419.
40. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129.
41. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37(6):1286-1292.
42. Portillo-Sanchez P, Bril F, Maximos M, et al. High prevalence of nonalcoholic fatty liver disease in patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab 2015;100(6):2231-2238.
43. Rodriguez V, Andrade AD, Garcia-Retamero R, et al. Health literacy, numeracy, and graphical literacy among veterans in primary care and their effect on shared decision making and trust in physicians. J Health Commun. 2013;18(suppl 1):273-289.
44. Kramer JR, Kanwal F, Richardson P, Mei M, El-Serag HB. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol. 2012;56(2):320-325.
45. Veterans Health Administration. Non-alcoholic fatty liver: information for patients. https://www.hepatitis.va.gov/pdf/NAFL.pdf. Published September 2017. Accessed November 7, 2018.
46. Armstrong MJ, Mottershead TA, Ronksley PE, Sigal RJ, Campbell TS, Hemmelgarn BR. Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2011;12(9):709-723.
47. Miller WR, Rollnick S. Motivational Interviewing: Helping People Change. Guilford Press: NY, New York; 2013.
48. Leventhal H, Leventhal EA, Breland JY. Cognitive science speaks to the “common sense” of chronic illness management. Ann Behav Med. 2011;41(2):152-163.
49. Zheng Y, Klem ML, Sereika SM, Danford CA, Ewing LJ, Burke LE. Self-weighing in weight management: a systematic literature review. Obesity (Silver Spring). 2015;23(2):256-265.
50. Steinberg DM, Bennett GG, Askew S, Tate DF. Weighing every day matters; daily weighing improves weight loss and adoption of weight control behaviors. J Acad Nutr Diet. 2015;115(4):511-518.
51. Charania MR, Marshall KJ, Lyles CM; HIV/AIDS Prevention Research Synthesis (PRS) Team. Identification of evidence-based interventions for promoting HIV medication adherence: findings from a systematic review of U.S.-based studies, 1996-2011. AIDS Behav. 2014;18(4):646-660.
52. Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet 2010;376(9755):1838-1845.
53. Dutton GR, Phillips JM, Kukkamalla M, Cherrington AL, Safford MM. Pilot study evaluating the feasibility and initial outcomes of a primary care weight loss intervention with peer coaches. Diabetes Educ. 2015:41(3):361-368.
54. Fisher EB, Coufal MM, Parada H, et al. Peer support in health care and prevention: Cultural, organizational, and dissemination issues. Annu Rev Public Health. 2014;35(1):363-383.
55. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;(346):393-403.
56. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.
57. Moin T, Ertl K, Schneider J, et al. Women veterans’ experience with a web-based diabetes prevention program: a qualitative study to inform future practice. J Med Internet Res. 2015;17(5):e127.
58. US Department of Veterans Affairs. MOVE! Weight management program. https://www.move.va.gov/MOVE/index.asp. Updated October 5, 2018. Accessed November 7, 2018.
59. Maciejewski ML, Arterburn DE, Van Scoyoc L, et al. Bariatric surgery and long-term durability of weight loss. JAMA Surg. 2016;151(11):1046-1055.
60. Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377(12):1143-1155.
61. Dimick JB, Nicholas LH, Ryan AM, Thumma JR, Birkmeyer JD. Bariatric surgery complications beforevs after implementation of a national policy restricting coverage to centers of excellence. JAMA. 2013;309(8):792-799.
62. The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-454.
63. Brito JP, Montori VM, Davis AM; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. JAMA. 2017;317(6):635-636.
64. Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(10):897-901.
65. Saab S, Mallam D, Cox GA 2nd, Tong MJ. Impact of coffee on liver diseases: a systematic review. Liver Int. 2014;34(4):495-504.
66. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59(1):138-143.
67. Musso G, Gambino R, Cassader M, Pagano G. A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52(1):79-104.
68. Patel Y, Gifford EJ, Glass LM, et al. Risk factors for biopsy-proven non-alcoholic fatty liver disease progression in the Veterans Health Administration. Aliment Pharmacol Ther. 2018;47(2):268-278.
Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (
In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.19
Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.24 When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.25 Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.26
In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.
Screening for Advanced Fibrosis
Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).29
Does This Patient Have NAFLD?
To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).16
Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated.
Evaluation of fasting glucose or hemoglobin A1c (HbA1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.16 Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.39
In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.
Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.16
Encouraging Patients to Pursue Intensive Lifestyle InterventionS
Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.43,44
In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.46
To start the conversation, the health care provider can explain that
- Why would you want to lose weight and exercise?
- How might you go about it in order to succeed?
- What are the 3 best reasons for you to do it?
- How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
- The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
- So what do you think you will do?
Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.47
This personalized action plan facilitates successful health behavior change.48 Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.49 In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.50 This simple daily measure seems to reinforce a patient’s action plan.
Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.51 For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.52 In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.
Effective VHA interventions
In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).55 In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.55 Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.56 To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.57
To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.58 Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.
In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.26 In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.59 Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.60 The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.63,64
Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.11,67
Conclusion
Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).2
NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.
Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.3,16,18 Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.68 The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.55
To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.33,37
In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.
Nonalcoholic fatty liver disease (NAFLD) is a silent epidemic affecting nearly 1 in 3 Americans and is increasing within the Veterans Health Administration (VHA).1,2 NAFLD independently increases the risk of type 2 diabetes mellitus (
In most patients (80%), NAFLD progresses slowly over decades. The progression is related to continuing insulin resistance.15,16 Greater disease progression is seen in patients with T2DM or concomitant chronic liver disease (such as hepatitis C).10,11,16 Patients with NAFLD who develop advanced fibrosis or cirrhosis experience increased rates of overall mortality, liver-related events, and liver transplantation.1,9,17,18 Within the VHA, NAFLD is the third most common cause of cirrhosis and HCC, occurring at an average age of 66 and 70 years, respectively.19
Although no pharmaceuticals are yet approved to treat NAFLD, even modest weight loss is beneficial. For example, weight loss > 4% improves fatty liver, ≥ 7% improves liver inflammation, and ≥ 10% decreases liver fibrosis (or scarring).21-23 In patients with a prior lack of success with weight loss, weight loss medications may be beneficial for short-term use.24 When comparing the effects of diet, exercise, obesity pharmacotherapy, and combinations for these approaches, intensive lifestyle modification with exercise had the greatest, most enduring benefit.25 Additionally, bariatric (weight loss) surgery has significantly improved health and liver-related outcomes for patients with NASH.26
In at-risk veterans, NAFLD has myriad negative effects on health and QOL. To improve its early identification and management in the VHA, we summarize strategies that all providers can use to screen and treat patients for this condition.
Screening for Advanced Fibrosis
Advanced fibrosis in NAFLD is diagnosed by analyzing adequately sized liver biopsies.27,28 However, noninvasive approaches to quantify advanced fibrosis by imaging or use of a simple fibrosis prediction score also are available. Imaging modalities include measuring liver stiffness, using transient elastography (FibroScan, Waltham, MA) or magnetic resonance elastography.1,29-31 Fibrosis prediction scores use common clinical and laboratory data to predict the presence or absence of advanced fibrosis (Table 1).29
Does This Patient Have NAFLD?
To identify NAFLD, patients with metabolic syndrome and modest or no alcohol use are first assessed for liver injury with ALT, AST, and complete blood count (Figure 3; Case 1).16
Next, common underlying liver diseases that cause liver injury should be excluded by hepatitis B and C virus serology.11,16 Other underlying liver diseases are uncommon and should be assessed only if clinically indicated.
Evaluation of fasting glucose or hemoglobin A1c (HbA1c)can identify undiagnosed T2DM. NAFL, or simple steatosis, is independently associated with an increased risk of T2DM, cardiovascular and kidney disease, yet not overall mortality.16 Over 10 to 20 years, few patients (4%) with simple steatosis progress to cirrhosis.39
In NAFLD, simple steatosis can resolve, and NASH can significantly improve with 7% to 10% weight loss.16,23,40 Patients with simple steatosis on imaging and normal liver enzymes should be monitored with periodic liver enzymes and fibrosis prediction scores (eg, FIB-4) and encouraged to pursue intensive lifestyle intervention.16,33 Without weight loss and exercise interventions metabolic syndrome, T2DM, and NAFLD may progress.
Patients with combined liver steatosis and liver enzyme elevations may exhibit NASH and warrant an evaluation by a hepatologist or gastroenterologist for consideration of additional testing or liver biopsy.16
Encouraging Patients to Pursue Intensive Lifestyle InterventionS
Most veterans wish to collaborate in their care (Table 3, Figure 4) yet experience many barriers, such as low health literacy, high rates of comorbidities, and ongoing drug/alcohol misuse.43,44
In addition to patient education, motivational interviewing significantly improves weight loss, resulting in a 3.3 lb (1.5 kg) increased weight loss in the intervention group vs the control group in weight loss studies.46
To start the conversation, the health care provider can explain that
- Why would you want to lose weight and exercise?
- How might you go about it in order to succeed?
- What are the 3 best reasons for you to do it?
- How important is it for you to make this change, and why? The provider can also ask the patient to quantify on a scale of 1 to 10: (a) How likely is it that they will make each required change? (b) How hard will each change be for them?
- The provider then summarizes the patient’s reasons for wanting change, how he/she can effect change, what their best reasons are, and how to successfully change. The provider then asks a final question:
- So what do you think you will do?
Most patients report feeling engaged, empowered, open, and understood with motivational interviewing. People are “persuaded by what they hear themselves say,” increasing motivation to change.47
This personalized action plan facilitates successful health behavior change.48 Action plans should integrate daily routines. For example, by placing the scale near the toothbrush, daily weighing is encouraged. Daily weighing is associated with significantly greater weight loss and less weight regain.49 In a 6-month, randomized controlled weight loss trial in men and women, daily weighing (using a scale that automatically transmitted weight data), with weekly e-mails and tailored feedback yielded an overall 9% weight loss and increased use of exercise and diet behaviors associated with weight loss in comparison with those who weighed themselves less than weekly.50 This simple daily measure seems to reinforce a patient’s action plan.
Adherence to an action plan significantly improves with patient education, peer or social support, and addressing barriers to adherence.51 For example, by providing support with weekly text messaging of “How are you?” and addressing the issues that patients reported in a large randomized treatment trial, adherence was significantly improved.52 In VHA patients with low health literacy, peer support or telephone coaching also has proven effective in increasing weight loss and glycemic control in patients with T2DM.53,54 Providing multidisciplinary team support during intensive lifestyle intervention, providers can partner with patients to address questions or issues and applaud progress.
Effective VHA interventions
In an ethnically diverse population of patients with prediabetes, up to 7% weight loss was observed in the Diabetes Prevention Program (DPP).55 In this study patients were randomized to placebo; metformin 850 mg twice daily; or a lifestyle-modification program in which they received one-on-one culturally sensitive, individualized lessons in diet, moderate exercise (≥ 150 minutes weekly), and behavior modification from case managers over 16 sessions. Lessons were reinforced in both group and individual sessions. This intervention was associated with an average of 6% weight loss at 6 months (half of participants attained 7% weight loss) and a 58% decrease in the rate of progression to T2DM over a nearly 3-year follow-up of this population with prediabetes compared with that of the placebo group.55 Over a 15-year follow-up, the intensive lifestyle intervention group sustained a 27% decrease in the incidence of T2DM compared with that of the placebo group.56 To emulate the success of the DPP in the VHA, a web-based DPP-like study in female veterans was performed with online coaching and daily weighing. This study achieved a 5.2% weight loss from baseline at 4 months.57
To improve outcomes, the VHA MOVE! Weight Management Program has been revised to include more sustained intervention (16 sessions) and multiple modes for participating—in person, by telephone, via video, via MOVE! Coach phone app, or any combination.58 Using shared decision making between patients with NAFLD and their providers, a customized MOVE! weight loss program can be developed to enable sustained intensive lifestyle intervention: hypocaloric diet, ≥ 150 minutes of moderate exercise weekly, and behavioral change.
In addition to intensive lifestyle intervention, a prospective study found that bariatric surgery significantly improved outcomes in patients with NASH, with most patients experiencing resolution of their NASH and nearly half exhibiting significantly improved fibrosis.26 In the VHA, bariatric surgery has yielded excellent long-term outcomes, with 21% sustained weight loss from baseline (vs matched nonsurgical population) at 10 years postoperatively in patients undergoing Roux-en-Y gastric bypass.59 Bariatric surgery also results in long-term remission of T2DM in most patients and significant improvement in hypertension and dyslipidemia.60 The risks of bariatric surgery include 3% serious complications, 1% reoperation rates, and 0.4% 30-day mortality.61,62 Bariatric surgery can be considered in patients with BMI > 40 or in patients with BMI > 35 who have comorbidities and do not have decompensated cirrhosis.63,64
Beyond weight loss, more favorable liver-related outcomes and lower rates of advanced liver fibrosis are observed in those consuming filtered coffee; a reduction in liver steatosis also is observed with adherence to a Mediterranean diet.65,66 In NAFLD, statins may improve liver chemistries and fibrosis; this class of medications can be used safely even in the presence of an elevated ALT.11,67
Conclusion
Nonalcoholic fatty liver disease independently increases the risk of T2DM, cardiovascular disease and kidney disease. With its rates increasing in the VHA, earlier identification and intervention is warranted in patients at high risk (ie, those with metabolic syndrome, obesity, and T2DM).2
NASH is more frequent in those with liver enzyme elevations or with an elevated FIB-4 and is associated with a long-term risk of cirrhosis. These patients merit referral to hepatology or gastroenterology for further evaluation and consideration of a liver biopsy to identify NASH. Patients with likely NAFLD without liver enzyme elevations can be further evaluated with FIB-4 scores to assess their probability of advanced liver fibrosis and potential need for referral to hepatology or gastroenterology.
Early NAFLD detection and intervention with intensive lifestyle modifications has the potential to avert progression to advanced fibrosis—and its associated increased overall and liver-related mortality, and impaired QOL.3,16,18 Although FIB-4 is a validated predictor of advanced fibrosis, this score is not yet used nationally to identify and risk stratify NAFLD in the VHA. Additionally, the very low use of VHA diet/exercise programs in eligible patients contributes to NAFLD progression.68 The cost-effective DPP has successfully yielded weight loss in patients with prediabetes and decreases in the incidence of T2DM through motivational interviewing and intensive lifestyle intervention.55
To improve NAFLD management, providers can successfully engage patients through motivational interviewing for intensive lifestyle intervention. Their resulting weight loss is enhanced with a personalized action plan, daily weighing, and peer support. When NAFLD is identified in patients with metabolic risk factors, the probability of advanced fibrosis is easily assessed in those with elevated FIB-4 scores who merit gastrointestinal referral.33,37
In all those identified with NAFLD, disease information should be provided to patients and their families. Intensive lifestyle modification targeting a ≥ 7% weight loss is recommended; motivational interviewing can increase commitment to change and yield a customized action plan for sustained weight loss. Working with the support and encouragement of their team of primary care providers, dieticians, and MOVE! coaches, patients can actively engage to improve their NAFLD and overall health.
1. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273.
2. Kanwal F, Kramer JR, Duan Z, et al. Trends in the burden of nonalcoholic fatty liver disease in a United States cohort of veterans. Clin Gastroenterol Hepatol. 2016;14(2):301-308.
3. Golabi P, Otgonsuren M, Cable R, et al. Non-alcoholic fatty liver disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL). Health Qual Life Outcomes. 2016;14(1):18.
4. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30(5):1212-1218.
5. Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13(4):511-531.
6. Centers for Disease Control and Prevention. About Prediabetes & Type 2 Diabetes. https://www.cdc.gov/diabetes/prevention/prediabetes-type2/index.html. Updated June 11, 2018. Accessed November 7, 2018.
7. Littman AJ, Jacobson IG, Boyko EJ, Powell TM, Smith TC; Millennium Cohort Study Team. Weight change following US military service. Int J Obes (Lond). 2013;37(2):244-253.
8. Breland JY, Phibbs CS, Hoggatt KJ, et al. The obesity epidemic in the Veterans Health Administration: prevalence among key populations of women and men veterans. J Gen Intern Med. 2017;32(suppl 1):11-17.
9. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854.
10. Bazick J, Donithan M, Neuschwander-Tetri BA, et al. Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care. 2015;38(7):1347-1355.
11. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
12. Bril F, Barb D, Portillo‐Sanchez P, et al. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease. Hepatology. 2017;65(4):1132-1144.
13. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017;377(21):2063-2072.
14. Nasr P, Ignatova S, Kechagias S, Ekstedt M. Natural history of nonalcoholic fatty liver disease: a prospective follow-up study with serial biopsies. Hepatol Commun. 2018;27(2):199-210.
15. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643-654.
16. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402.
17. Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577-1586.
18. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-397.
19. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US Veterans, 2001-2013. Gastroenterology 2015;149(6):1471-1482.
20. Mittal S, El-Serag HB, Sada YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14(1):124-131.
21. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol. 2017;4(1):e000139.
22. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56(1):255-266.
23. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
24. Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.
25. Haw JS, Galaviz KI, Straus AN, et al. Long-term sustainability of diabetes prevention approaches: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2017;177(12):1808-1817.
26. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379-388.
27. Kleiner DE, Brunt EM, Van Natta M, et al; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321.
28. Bedossa P; FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology. 2014;60(2):565-567.
29. Tapper EB, Sengupta N, Hunink MG, Afdhal NH, Lai M. Cost-effective evaluation of nonalcoholic fatty liver disease with NAFLD fibrosis score and vibration controlled transient elastography. Am J Gastroenterol. 2015;110(9):1298-1304.
30. Cui J, Ang B, Haufe W, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non‐invasive diagnosis of advanced fibrosis in biopsy‐proven non‐alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271-1280.
31. Tapper EB, Lok AS-F. Use of liver imaging and biopsy in clinical practice. N Engl J Med . 2017;377(8):756-768.
32. Sterling RK, Lissen E, Clumeck N; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-1325.
33. Imler T. Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/fibrosis-4-score. Published 2018. Accessed November 7, 2018.
34. Sun W, Cui H , Li N, et al. Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: a meta-analysis study. Hepatol Res. 2016;46(9):862-870.
35. Imler T, Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/nafld-fibrosis-score. Published 2018. Accessed November 7, 2018.
36. Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441-1447.
37. Patel YA, Gifford EJ, Glass LM, et al. Identifying non-alcoholic fatty liver disease advanced fibrosis in the Veterans Health Administration. Dig Dis Sci. 2018;63(9): 2259-2266.
38. Armstrong MJ, Houlihan DD, Bentham L, et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J Hepatol. 2012;56(1):234-240.
39. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413-1419.
40. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129.
41. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37(6):1286-1292.
42. Portillo-Sanchez P, Bril F, Maximos M, et al. High prevalence of nonalcoholic fatty liver disease in patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab 2015;100(6):2231-2238.
43. Rodriguez V, Andrade AD, Garcia-Retamero R, et al. Health literacy, numeracy, and graphical literacy among veterans in primary care and their effect on shared decision making and trust in physicians. J Health Commun. 2013;18(suppl 1):273-289.
44. Kramer JR, Kanwal F, Richardson P, Mei M, El-Serag HB. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol. 2012;56(2):320-325.
45. Veterans Health Administration. Non-alcoholic fatty liver: information for patients. https://www.hepatitis.va.gov/pdf/NAFL.pdf. Published September 2017. Accessed November 7, 2018.
46. Armstrong MJ, Mottershead TA, Ronksley PE, Sigal RJ, Campbell TS, Hemmelgarn BR. Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2011;12(9):709-723.
47. Miller WR, Rollnick S. Motivational Interviewing: Helping People Change. Guilford Press: NY, New York; 2013.
48. Leventhal H, Leventhal EA, Breland JY. Cognitive science speaks to the “common sense” of chronic illness management. Ann Behav Med. 2011;41(2):152-163.
49. Zheng Y, Klem ML, Sereika SM, Danford CA, Ewing LJ, Burke LE. Self-weighing in weight management: a systematic literature review. Obesity (Silver Spring). 2015;23(2):256-265.
50. Steinberg DM, Bennett GG, Askew S, Tate DF. Weighing every day matters; daily weighing improves weight loss and adoption of weight control behaviors. J Acad Nutr Diet. 2015;115(4):511-518.
51. Charania MR, Marshall KJ, Lyles CM; HIV/AIDS Prevention Research Synthesis (PRS) Team. Identification of evidence-based interventions for promoting HIV medication adherence: findings from a systematic review of U.S.-based studies, 1996-2011. AIDS Behav. 2014;18(4):646-660.
52. Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet 2010;376(9755):1838-1845.
53. Dutton GR, Phillips JM, Kukkamalla M, Cherrington AL, Safford MM. Pilot study evaluating the feasibility and initial outcomes of a primary care weight loss intervention with peer coaches. Diabetes Educ. 2015:41(3):361-368.
54. Fisher EB, Coufal MM, Parada H, et al. Peer support in health care and prevention: Cultural, organizational, and dissemination issues. Annu Rev Public Health. 2014;35(1):363-383.
55. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;(346):393-403.
56. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.
57. Moin T, Ertl K, Schneider J, et al. Women veterans’ experience with a web-based diabetes prevention program: a qualitative study to inform future practice. J Med Internet Res. 2015;17(5):e127.
58. US Department of Veterans Affairs. MOVE! Weight management program. https://www.move.va.gov/MOVE/index.asp. Updated October 5, 2018. Accessed November 7, 2018.
59. Maciejewski ML, Arterburn DE, Van Scoyoc L, et al. Bariatric surgery and long-term durability of weight loss. JAMA Surg. 2016;151(11):1046-1055.
60. Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377(12):1143-1155.
61. Dimick JB, Nicholas LH, Ryan AM, Thumma JR, Birkmeyer JD. Bariatric surgery complications beforevs after implementation of a national policy restricting coverage to centers of excellence. JAMA. 2013;309(8):792-799.
62. The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-454.
63. Brito JP, Montori VM, Davis AM; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. JAMA. 2017;317(6):635-636.
64. Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(10):897-901.
65. Saab S, Mallam D, Cox GA 2nd, Tong MJ. Impact of coffee on liver diseases: a systematic review. Liver Int. 2014;34(4):495-504.
66. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59(1):138-143.
67. Musso G, Gambino R, Cassader M, Pagano G. A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52(1):79-104.
68. Patel Y, Gifford EJ, Glass LM, et al. Risk factors for biopsy-proven non-alcoholic fatty liver disease progression in the Veterans Health Administration. Aliment Pharmacol Ther. 2018;47(2):268-278.
1. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273.
2. Kanwal F, Kramer JR, Duan Z, et al. Trends in the burden of nonalcoholic fatty liver disease in a United States cohort of veterans. Clin Gastroenterol Hepatol. 2016;14(2):301-308.
3. Golabi P, Otgonsuren M, Cable R, et al. Non-alcoholic fatty liver disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL). Health Qual Life Outcomes. 2016;14(1):18.
4. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30(5):1212-1218.
5. Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13(4):511-531.
6. Centers for Disease Control and Prevention. About Prediabetes & Type 2 Diabetes. https://www.cdc.gov/diabetes/prevention/prediabetes-type2/index.html. Updated June 11, 2018. Accessed November 7, 2018.
7. Littman AJ, Jacobson IG, Boyko EJ, Powell TM, Smith TC; Millennium Cohort Study Team. Weight change following US military service. Int J Obes (Lond). 2013;37(2):244-253.
8. Breland JY, Phibbs CS, Hoggatt KJ, et al. The obesity epidemic in the Veterans Health Administration: prevalence among key populations of women and men veterans. J Gen Intern Med. 2017;32(suppl 1):11-17.
9. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854.
10. Bazick J, Donithan M, Neuschwander-Tetri BA, et al. Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care. 2015;38(7):1347-1355.
11. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357.
12. Bril F, Barb D, Portillo‐Sanchez P, et al. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease. Hepatology. 2017;65(4):1132-1144.
13. Diehl AM, Day C. Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. N Engl J Med. 2017;377(21):2063-2072.
14. Nasr P, Ignatova S, Kechagias S, Ekstedt M. Natural history of nonalcoholic fatty liver disease: a prospective follow-up study with serial biopsies. Hepatol Commun. 2018;27(2):199-210.
15. Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643-654.
16. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402.
17. Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology. 2016;64(5):1577-1586.
18. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389-397.
19. Beste LA, Leipertz SL, Green PK, Dominitz JA, Ross D, Ioannou GN. Trends in burden of cirrhosis and hepatocellular carcinoma by underlying liver disease in US Veterans, 2001-2013. Gastroenterology 2015;149(6):1471-1482.
20. Mittal S, El-Serag HB, Sada YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14(1):124-131.
21. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol. 2017;4(1):e000139.
22. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56(1):255-266.
23. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-378.
24. Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.
25. Haw JS, Galaviz KI, Straus AN, et al. Long-term sustainability of diabetes prevention approaches: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2017;177(12):1808-1817.
26. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379-388.
27. Kleiner DE, Brunt EM, Van Natta M, et al; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321.
28. Bedossa P; FLIP Pathology Consortium. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology. 2014;60(2):565-567.
29. Tapper EB, Sengupta N, Hunink MG, Afdhal NH, Lai M. Cost-effective evaluation of nonalcoholic fatty liver disease with NAFLD fibrosis score and vibration controlled transient elastography. Am J Gastroenterol. 2015;110(9):1298-1304.
30. Cui J, Ang B, Haufe W, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non‐invasive diagnosis of advanced fibrosis in biopsy‐proven non‐alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271-1280.
31. Tapper EB, Lok AS-F. Use of liver imaging and biopsy in clinical practice. N Engl J Med . 2017;377(8):756-768.
32. Sterling RK, Lissen E, Clumeck N; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-1325.
33. Imler T. Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/fibrosis-4-score. Published 2018. Accessed November 7, 2018.
34. Sun W, Cui H , Li N, et al. Comparison of FIB-4 index, NAFLD fibrosis score and BARD score for prediction of advanced fibrosis in adult patients with non-alcoholic fatty liver disease: a meta-analysis study. Hepatol Res. 2016;46(9):862-870.
35. Imler T, Indiana University School of Medicine - GIHep calculators. http://gihep.com/calculators/hepatology/nafld-fibrosis-score. Published 2018. Accessed November 7, 2018.
36. Harrison SA, Oliver D, Arnold HL, Gogia S, Neuschwander-Tetri BA. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441-1447.
37. Patel YA, Gifford EJ, Glass LM, et al. Identifying non-alcoholic fatty liver disease advanced fibrosis in the Veterans Health Administration. Dig Dis Sci. 2018;63(9): 2259-2266.
38. Armstrong MJ, Houlihan DD, Bentham L, et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J Hepatol. 2012;56(1):234-240.
39. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413-1419.
40. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129.
41. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37(6):1286-1292.
42. Portillo-Sanchez P, Bril F, Maximos M, et al. High prevalence of nonalcoholic fatty liver disease in patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab 2015;100(6):2231-2238.
43. Rodriguez V, Andrade AD, Garcia-Retamero R, et al. Health literacy, numeracy, and graphical literacy among veterans in primary care and their effect on shared decision making and trust in physicians. J Health Commun. 2013;18(suppl 1):273-289.
44. Kramer JR, Kanwal F, Richardson P, Mei M, El-Serag HB. Gaps in the achievement of effectiveness of HCV treatment in national VA practice. J Hepatol. 2012;56(2):320-325.
45. Veterans Health Administration. Non-alcoholic fatty liver: information for patients. https://www.hepatitis.va.gov/pdf/NAFL.pdf. Published September 2017. Accessed November 7, 2018.
46. Armstrong MJ, Mottershead TA, Ronksley PE, Sigal RJ, Campbell TS, Hemmelgarn BR. Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2011;12(9):709-723.
47. Miller WR, Rollnick S. Motivational Interviewing: Helping People Change. Guilford Press: NY, New York; 2013.
48. Leventhal H, Leventhal EA, Breland JY. Cognitive science speaks to the “common sense” of chronic illness management. Ann Behav Med. 2011;41(2):152-163.
49. Zheng Y, Klem ML, Sereika SM, Danford CA, Ewing LJ, Burke LE. Self-weighing in weight management: a systematic literature review. Obesity (Silver Spring). 2015;23(2):256-265.
50. Steinberg DM, Bennett GG, Askew S, Tate DF. Weighing every day matters; daily weighing improves weight loss and adoption of weight control behaviors. J Acad Nutr Diet. 2015;115(4):511-518.
51. Charania MR, Marshall KJ, Lyles CM; HIV/AIDS Prevention Research Synthesis (PRS) Team. Identification of evidence-based interventions for promoting HIV medication adherence: findings from a systematic review of U.S.-based studies, 1996-2011. AIDS Behav. 2014;18(4):646-660.
52. Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet 2010;376(9755):1838-1845.
53. Dutton GR, Phillips JM, Kukkamalla M, Cherrington AL, Safford MM. Pilot study evaluating the feasibility and initial outcomes of a primary care weight loss intervention with peer coaches. Diabetes Educ. 2015:41(3):361-368.
54. Fisher EB, Coufal MM, Parada H, et al. Peer support in health care and prevention: Cultural, organizational, and dissemination issues. Annu Rev Public Health. 2014;35(1):363-383.
55. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;(346):393-403.
56. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.
57. Moin T, Ertl K, Schneider J, et al. Women veterans’ experience with a web-based diabetes prevention program: a qualitative study to inform future practice. J Med Internet Res. 2015;17(5):e127.
58. US Department of Veterans Affairs. MOVE! Weight management program. https://www.move.va.gov/MOVE/index.asp. Updated October 5, 2018. Accessed November 7, 2018.
59. Maciejewski ML, Arterburn DE, Van Scoyoc L, et al. Bariatric surgery and long-term durability of weight loss. JAMA Surg. 2016;151(11):1046-1055.
60. Adams TD, Davidson LE, Litwin SE, et al. Weight and metabolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377(12):1143-1155.
61. Dimick JB, Nicholas LH, Ryan AM, Thumma JR, Birkmeyer JD. Bariatric surgery complications beforevs after implementation of a national policy restricting coverage to centers of excellence. JAMA. 2013;309(8):792-799.
62. The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-454.
63. Brito JP, Montori VM, Davis AM; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. JAMA. 2017;317(6):635-636.
64. Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(10):897-901.
65. Saab S, Mallam D, Cox GA 2nd, Tong MJ. Impact of coffee on liver diseases: a systematic review. Liver Int. 2014;34(4):495-504.
66. Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59(1):138-143.
67. Musso G, Gambino R, Cassader M, Pagano G. A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010;52(1):79-104.
68. Patel Y, Gifford EJ, Glass LM, et al. Risk factors for biopsy-proven non-alcoholic fatty liver disease progression in the Veterans Health Administration. Aliment Pharmacol Ther. 2018;47(2):268-278.
A Veteran With Acute Progressive Encephalopathy of Unknown Etiology
Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.
► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?
►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.
►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?
►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.1 In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.
►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1). 
Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?
►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.
►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.
Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?
►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.2
►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?
►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.
►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2). 
Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?
►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.
►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer. 
Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?
►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.5 The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.6
►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?
►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.7
►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.
This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.
Acknowledgments
We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.
1. Heldner MR, Zubler C, Mattle HP, et al. National Institutes of Health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke. Stroke. 2013;44(4):1153-1157.
2. Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol. 2015;32(2):87-95.
3. DeBiasi RL, Kleinschmidt-DeMasters BK, Weinberg A, Tyler KL. Use of PCR for the diagnosis of herpesvirus infections of the central nervous system. J Clin Virol. 2002;25(suppl 1):S5-S11.
4. Buerger KJ, Zerr K, Salazar R. An unusual presentation of herpes simplex encephalitis with negative PCR. BMJ Case Rep. 2015;2015:pii:bcr201521052.
5. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.
6. Greenlee JE, Clawson SA, Hill KE, et al. Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures. J Neuroinflammation. 2014;11:160.
7. Bradshaw MJ, Linnoila JJ. An overview of autoimmune and paraneoplastic encephalitides. Semin Neurol. 2018;38(3):330-343.
Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.
► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?
►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.
►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?
►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.1 In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.
►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1).
Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?
►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.
►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.
Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?
►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.2
►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?
►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.
►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2).
Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?
►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.
►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer.
Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?
►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.5 The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.6
►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?
►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.7
►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.
This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.
Acknowledgments
We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.
Case Presentation. A 70-year-old US Marine Corps veteran of the Vietnam War with no significant past medical history was brought by ambulance to VA Boston Healthcare System (VABHS) after being found on the floor at home by his wife, awake, but with minimally coherent speech. He was moving all extremities, and there was no loss of bowel or bladder continence. He had last been seen well by his wife 30 minutes prior. When emergency medical services arrived, his finger stick blood glucose and vital signs were within normal range. In the emergency department, he was able to state his first name but then continuously repeated “7/11” to other questions. A neurologic examination revealed intact cranial nerves, full strength in all extremities, and normal reflexes. A National Institute of Health Stroke Scale (NIHSS) was 3, and a code stroke was activated. At the time of presentation, the patient was an active smoker of 15 cigarettes per day for 50 years and did not use alcohol or recreational drugs.
► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. Fehnel, the patient’s medical team was most worried about a transient ischemic attack (TIA) or cerebrovascular accident (CVA). Is his presentation consistent with these diagnoses, and what else is on your differential diagnosis?
►Corey R. Fehnel, MD, Neuro-Intensivist, BIDMC, and Assistant Professor of Neurology, Harvard Medical School. This patient is presenting with what appears to be an acute encephalopathy—a sudden onset of global alteration in mental status. The most worrisome underlying etiology for this presentation would be acute stroke, but this is an uncommon cause of acute encephalopathy. The differential diagnosis at this stage remains broad, but a careful neurologic examination can help narrow the possibilities. In particular, I would aim to differentiate an apparent language deficit (ie, aphasia) from a deficit of attention. A key finding that may help is the ability to name high- or low-frequency objects. If the patient can successfully name objects, aphasia is less likely. Based on the limited examination at present, the patient produces some normal speech, but perseverates; therefore, the finding remains nonspecific. My leading diagnoses are complex partial seizure and toxic/metabolic encephalopathy.
►Dr. Li. This patient’s NIHSS score is 3. How do you use this score in your management decisions for the patient?
►Dr. Fehnel. The NIHSS is a useful tool for gauging severity of ischemic and hemorrhagic stroke. However the score is not specific for establishing the diagnosis of stroke. Many common and chronic neurologic problems will score on the NIHSS, so it can never be interpreted in isolation. If the clinical history and complete neurologic examination support the diagnosis of stroke, then the NIHSS can be used with the understanding that it is biased toward anterior circulation strokes, and posterior circulation strokes will score lower even though they are potentially more life threatening.1 In this case, even though a complex partial seizure appears more likely, it is difficult to rule out the possibility of an acute stroke affecting the thalamus or, less likely, a distal middle cerebral artery occlusion. I would consider IV thrombolysis pending further history and neuroimaging results.
►Dr. Li. Initial laboratory data include a hemoglobin of 12.8 mg/dL. The white cell count, platelet count, chemistry panel, liver function tests, thyroid-stimulating hormone, and troponin were within normal range (Table 1).
Do you agree with inpatient workup for this patient whose mental status has now returned to baseline? If so, what workup would you pursue next?
►Dr. Fehnel. This patient requires inpatient admission to further evaluate the underlying etiology for his acute change in mental status. The improvement of his presenting deficit and largely normal neurovascular imaging make a neurovascular etiology less likely, but a careful risk factor evaluation for CVA/TIA should be performed, including continuous cardiac telemetry to detect atrial fibrillation. Magnetic resonance imaging (MRI) of the brain should be performed to rule out occult stroke and evaluate for a structural etiology given the more likely diagnosis of complex partial seizure. An electroencephalogram (EEG), preferably 24-hour continuous recording, should be performed. Without a clear toxic or metabolic etiology thus far to explain his acute global waxing-waning alteration in mental status and likely new-onset complex partial seizures, I would also pursue lumbar puncture for cerebrospinal fluid examination.
►Dr. Li. The hospital course was notable for episodes of acute combativeness and confusion. An MRI of the brain was deferred due to reports from the patient’s family of retained shrapnel in the lumbar spine. Routine EEG showed no seizure activity. This was followed by continuous video EEG monitoring, which showed subclinical seizure activity with a right temporal focus. He was started on valproic acid with improvement in his agitation, though confusion continued. He was discharged to an inpatient geriatric psychiatry nursing home with diagnosis of seizures and acute delirium.
Dr. Fehnel, seizures are often part of the workup for unexplained encephalopathy. In this case, the routine EEG was unrevealing, while the continuous video EEG proved valuable. In what situations would you pursue a continuous video EEG in addition to a routine EEG?
►Dr. Fehnel. EEG monitoring is only as good as the window of time during which the study is performed. If the suspicious clinical event is captured during a routine recording or an area of focal slowing is detected, a shorter study may be entirely sufficient. However, in cases where there is no clear alternative explanation, a patient’s mental status does not return to normal, or in the setting of mental status fluctuations without explanation, continuous video-EEG monitoring for at least 24 hours is indicated. While the prolonged study raises sensitivity, the exact duration of EEG recording required outside of the intensive care unit setting remains debated.2
►Dr. Li. If his encephalopathy were due to seizures alone, I would expect improvement in his mental status during interictal periods, which does not appear to be the case here. Do you feel the seizures alone can explain his encephalopathy?
►Dr. Fehnel. Complex partial seizures and the medications used to treat them can confound the examination of patients during the interictal period. We commonly debate postictal encephalopathy vs residual effect of benzodiazepines and rapid dose escalation of antiepileptic drugs as culprit in a patient’s prolonged alteration in mental status. Serial clinical examinations, continuous EEG monitoring to rule out ongoing subclinical seizures when appropriate, and judicious use of potentially sedating medications is the most helpful approach. The key issue here is the bimodal distribution of new-onset seizures. Among children there is a higher incidence of genetically related seizure disorders; whereas among adults, “acquired” and structural etiologies are more common. For this case, a more careful evaluation of acquired/structural etiologies for new-onset seizures is indicated.
►Dr. Li. At the geriatric psychiatry nursing home, the patient continued to be combative and refused medications. He was readmitted to the VABHS with encephalopathy of unclear etiology. An expanded encephalopathy workup was unrevealing (Table 2).
Dr. Fehnel, this patient’s initial cerebrospinal fluid (CSF) cell count and chemistries were completely normal. Is this sufficient to rule out encephalitis? If not, what other diagnostic tests would you send?
►Dr. Fehnel. A fully normal CSF profile reduces the likelihood of a broad range of neuro-infectious etiologies but does not completely rule those out. For example, there are reports of herpes simplex virus (HSV) encephalitis producing relatively normal profiles and even negative polymerase chain reaction assays for antibodies to HSV if the specimen is obtained very early in the course of the disease.3,4 That was not the case here as the CSF was obtained several days after his initial presentation. Given this patient’s clinical syndrome, normal CSF findings, and long smoking history without regular screening examinations, I would send a CSF specimen screening for paraneoplastic and autoimmune encephalitis. Most autoimmune encephalitis syndromes are associated with CSF lymphocytic pleocytosis or slight elevation in CSF protein levels. This patient’s diagnosis is most likely an anti-Hu paraneoplastic syndrome, which can be distinguished from other autoimmune and paraneoplastic processes by the characteristically normal CSF profile. Anti-Hu antibodies are strongly associated with non-small cell lung cancer (NSCLC). I would, therefore, also obtain more advanced chest imaging.
►Dr. Li. An autoimmune and paraneoplastic encephalitis panel was sent. While this send-out panel was pending, a CT torso was obtained to evaluate for occult malignancy in light of his significant smoking history. This showed a 3-cm spiculated mass originating from the left hilum. Bronchoalviolar lavage washings returned positive for small cell lung cancer.
Dr. Fehnel, can you explain the mechanism by which certain neoplasms can cause encephalitis?
►Dr. Fehnel. Onconeuronal antibodies Hu (NSCLC) and Ma2 (testicular seminoma), when identified, are strongly associated with the presence of an underlying malignancy. The work of Dr. Josep Dalmau and others in this area has dramatically improved our understanding of these syndromes over the past 25 years.5 The exact mechanism is not fully understood but is thought to be mediated by cytotoxic T-cell response directed at the malignancy itself with homology to intraneuronal structures, which are readily absorbed and result in neuronal cell death.6
►Dr. Li. Is there a specific treatment for paraneoplastic encephalitis, other than treating the underlying malignancy?
►Dr. Fehnel. Early treatment is associated with improved outcome and should not be delayed while waiting for laboratory confirmation in cases of high clinical suspicion. Treatment directed at the underlying tumor is the mainstay along with less specific immunosuppressive agents. Unfortunately Anti-Hu (as well as Ma2) antibodies are intraneuronal and less responsive to standard treatments relative to other paraneoplastic auto-antibodies identified on the cell surface. Immunosuppressive agents typically used in this setting include high-dose IV methylprednisolone, IV immune globulin (IVIG), rituximab, and cyclophosphamide.7
►Dr. Li. The patient was started on IVIG, methylprednisolone, cisplatin, and etoposide. His course was complicated by aspiration pneumonia, autonomic dysfunction causing tachy- and brady-arrhythmias, urosepsis, worsening somnolence, chemotherapy-induced neutropenic fevers, and ultimately septic shock. The palliative care team was closely involved throughout the final stages of his hospital course. After multiple family meetings, the patient was transitioned to comfort-focused care per family discussion and died 6 weeks after his initial presentation.
This patient had a very atypical initial presentation of small cell lung cancer. Despite the fact that a diagnosis eluded his doctors, they persisted in a thoughtful and exhaustive workup and through this perseverance were able to make the final diagnosis, which serves as an important learning case for us all.
Acknowledgments
We thank the family of this veteran for sharing his story and allowing us to learn from this case for the benefit of our future patients. We also thank Dr. Michelle Hankins, who provided oncologic expertise.
1. Heldner MR, Zubler C, Mattle HP, et al. National Institutes of Health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke. Stroke. 2013;44(4):1153-1157.
2. Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol. 2015;32(2):87-95.
3. DeBiasi RL, Kleinschmidt-DeMasters BK, Weinberg A, Tyler KL. Use of PCR for the diagnosis of herpesvirus infections of the central nervous system. J Clin Virol. 2002;25(suppl 1):S5-S11.
4. Buerger KJ, Zerr K, Salazar R. An unusual presentation of herpes simplex encephalitis with negative PCR. BMJ Case Rep. 2015;2015:pii:bcr201521052.
5. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.
6. Greenlee JE, Clawson SA, Hill KE, et al. Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures. J Neuroinflammation. 2014;11:160.
7. Bradshaw MJ, Linnoila JJ. An overview of autoimmune and paraneoplastic encephalitides. Semin Neurol. 2018;38(3):330-343.
1. Heldner MR, Zubler C, Mattle HP, et al. National Institutes of Health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke. Stroke. 2013;44(4):1153-1157.
2. Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society. Consensus statement on continuous EEG in critically ill adults and children, part I: indications. J Clin Neurophysiol. 2015;32(2):87-95.
3. DeBiasi RL, Kleinschmidt-DeMasters BK, Weinberg A, Tyler KL. Use of PCR for the diagnosis of herpesvirus infections of the central nervous system. J Clin Virol. 2002;25(suppl 1):S5-S11.
4. Buerger KJ, Zerr K, Salazar R. An unusual presentation of herpes simplex encephalitis with negative PCR. BMJ Case Rep. 2015;2015:pii:bcr201521052.
5. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.
6. Greenlee JE, Clawson SA, Hill KE, et al. Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures. J Neuroinflammation. 2014;11:160.
7. Bradshaw MJ, Linnoila JJ. An overview of autoimmune and paraneoplastic encephalitides. Semin Neurol. 2018;38(3):330-343.
Meeting 21st Century Public Health Needs: Public Health Partnerships at the Uniformed Services University
The Uniformed Services University of the Health Sciences (USU) was established by Congress in 1972 under the Uniformed Services Health Professions Revitalization Act. The only medical school administered by the federal government, “America’s Medical School” as it is affectionately known, has a mission to educate, train, and comprehensively prepare uniformed services health professionals to support the US military and public health system.
The USU School of Medicine (SOM) matriculates about 170 students each year. Although the majority of the medical students receive commissions in the US Army, Navy, or Air Force and serve as military physicians in the Department of Defense (DoD), a small number of students each year are commissioned as officers in the US Public Health Service Commissioned Corps (PHS). The PHS is a uniformed service within the US Department of Health and Human Services (HHS) whose officers serve nationwide in more than 30 government agencies. However, unlike its sister DoD services, the PHS does not participate in the Health Professions Scholarship Program, so admission to USU represents the only direct accession to the PHS Commissioned Corps for prospective physicians.
Beginning with the first graduating class, more than 160 PHS physician officers have now been trained under agreements with PHS agencies and SOM, and numerous others have received training and experience from the other academic programs and research centers within USU. Ten of those graduates achieved the rank of Rear Admiral, the general officer or “flag” position of the PHS.
The benefits of the partnerships between USU, PHS, and the agencies served by PHS to public health outcomes are many. Specifically, investment in PHS students at the SOM has served to ease disparities experienced by American Indians and Alaskan Natives (AI/AN), combat the shortage of primary care physicians (PCPs), generate exceptional clinical researchers, and train health care professionals to be prepared and ready to respond to emerging threats to public health.
Addressing Health Care Disparities Experienced by AI/AN
Through numerous treaties, laws, court cases, and Executive Orders—and most recently reaffirmed by the reauthorization of the Indian Health Care Improvement Act as part of the Patient Protection and Affordable Care Act (2010)–the US federal government holds responsibility for the provision of medical services to AI/AN. The Indian Health Service (IHS) is the principal federal provider of health care services for the AI/AN population. The mission of the IHS is to raise the physical, mental, social, and spiritual health of the AI/AN population to the highest level. It seeks to accomplish this mission by assuring that comprehensive, culturally acceptable personal and public health services are available and accessible to all AI/AN people.
Agency partnerships at USU, like the one between the school and IHS, sponsor medical students to become PHS physicians who can combat health disparities, especially those experienced by AI/AN. AI/AN continue to be subjected to disparities in health status across a wide array of chronic conditions, with significantly higher mortality rates than those of white populations.1 These trends are driven by multifactorial etiologies, including social determinants of health,2 obesity and the metabolic syndrome,3 high rates of tobacco and alcohol use,4 and limited access to medical care.5
Recruitment and retention of health care providers (HCPs) has long been a challenge for the IHS.6 Despite many attractive factors, providing care in a setting of otherwise limited resources and the relative remoteness of most facilities may prove to be deterring factors to prospective applicants. Furthermore, promotion of quality providers to administrative roles and high turnover rates of contractors or temporary staff contribute to poor continuity of care in certain locations. Consequently, efforts are under way to increase provider retention and continuity of care for patients.
This effort is augmented by training officers for a career of service to the IHS within the PHS. After completion of medical school and a residency in primary care, IHS-sponsored graduates from USU serve as officers in the PHS, stationed at an IHS-designated high-priority site for 10 years.7 However, many stay with the IHS for much longer, like IHS Chief Medical Officer, RADM Michael Toedt (USU 1995). In fact, nearly all the officers commissioned in the past 20 years are still on active duty. Within the IHS, physicians focus on community-oriented practice and improving the health of small-town and rural residents at tribal or federally operated clinics and community hospitals. In addition to performing clinical duties, graduates frequently become leaders within the IHS, advocating for systemwide improvements, performing practice-based research, and improving the overall well-being of AI/AN communities.
Combating the PCP Shortage
It has been well documented that primary care is essential for the prevention and control of chronic disease.8 However, fewer US medical school graduates are choosing to practice in primary care specialties, and the number of PCPs is forecasted to be insufficient for the needs of the American population in the coming years.9,10 This deficit is predicted to be especially pronounced in rural and underserved communities.11
Training PHS officers at the USU can fill this growing need by cultivating PCPs committed to a career of service in areas of high need. PHS medical students who are sponsored to attend USU by the IHS select from 1 of 7 approved primary care residencies: emergency medicine, family medicine, general pediatrics, general internal medicine, general psychiatry, obstetrics/gynecology, and general surgery.7 PHS students are permitted to train at military or civilian graduate medical education programs; permission to pursue combination programs is granted on a case-by-case basis, with consideration for the needs of the agency. Previously, such authorizations have included internal medicine/pediatrics, internal medicine/psychiatry, and family medicine/preventive medicine. This requirement, understood at the time of matriculation, selects for students who are passionate about primary care and are willing to live and practice in rural, underserved areas during their 10-year service commitment to the agency.
During medical school, USU students participate in numerous training activities that prepare doctors for practice in isolated or resource-poor settings, including point-of-care ultrasonography and field exercises in stabilization and transport of critically ill patients. The motto of the SOM, “Learning to Care for Those in Harm’s Way,” thereby applies not only to battlefield medicine, but to those who practice medicine in austere environments of all kinds.
Generating Clinical Researchers
Although IHS currently funds most PHS students, sponsorship also is available through the National Institute of Allergy and Infectious Diseases (NIAID), one of the institutes of the National Institutes of Health (NIH) in Bethesda, Maryland. Students selected for this competitive program complete a residency in either internal medicine or pediatrics, then complete an NIH-sponsored fellowship in either infectious diseases or allergy and immunology. Similar to their IHS counterparts, they incur a debt of service—10 years in the PHS Commissioned Corps; however, their service obligation is served at NIH. This track supports the creation of the next generation of clinical researchers and physician-scientists, critical in this time of ever-increasing threats to public health and national security, like emerging infectious diseases and bioterrorism.
Emergency Response Preparations
Combined training with experts from DoD and HHS prepares junior medical officers to serve as leaders in responding to large-scale emergencies and disasters. According to a memorandum of December 11, 1981, then Surgeon General C. Everett Koop described the importance of this skill set, saying that USU students are “ready for instant mobilization to meet military [needs] and [respond to] national disasters.” He continued, “Students are taught the necessary leadership and management skills to command medical units and organizations in the delivery of health services...They are exposed to the problems of dealing with national medical emergencies such as floods, earthquakes, and mass immigrations to this country.”12 Fittingly, physician graduates of USU have recently led disaster response efforts for Hurricanes Harvey, Irma, and Maria and Typhoon Yutu.
Traditional medical school didactic coursework is supplemented by lectures on disaster response, emergency preparedness, and global health engagement. As training progresses, students translate their knowledge into action with practical fieldwork exercises in mass casualty triage, erection of field hospitals using preventive medicine principles, and containment of infectious disease outbreaks among displaced persons—under the close observation and guidance of military and public health subject matter experts from across the country. Medical students complete their clinical training at military treatment facilities around the country and have elective clerkship opportunities in operational medicine nationally and internationally. PHS graduates of USU are well prepared to interface with their military colleagues, building effective joint mission capacity.
Additional Training Opportunities
In addition to the 4-year, tuition-free MD program, the university offers 7 graduate degree programs in public health and residency programs in preventive medicine specialty areas. Continuing education opportunities and graduate certificates are available in global health, tropical medicine and hygiene, travelers’ health, international and domestic disaster response, and other fields of interest to any public health professional, military or civilian. Many programs are available to federal or uniformed service members at no cost, some incur a degree of service commitment. Furthermore, the university is home to multiple research centers, including the National Center for Disaster Medicine and Public Health, which strive to improve public health through research efforts and education.
Conclusion
Though the emerging public health needs of the nation are both varied and daunting, the USU/PHS partnership trains providers that will heed the call and face the modern public health needs head-on. USU remains an important source for commissioning PHS physicians and producing career officers. The unique training provided at USU educates and enables PHS physicians to ease disparities experienced by AI/AN, combat the shortage of PCPs, generate exceptional clinical researchers, and be prepared and ready to respond to emerging threats to public health.
1. Espey DK, Jim MA, Cobb N, et al. Leading causes of death and all-cause mortality in American Indians and Alaska natives. Am J Public Health . 2014;104(S3):S303-S311.
2. Kunitz SJ, Veazie M, Henderson JA. Historical trends and regional differences in all-cause and amenable mortality among American Indians and Alaska Natives since 1950. Am J Public Health. 2014;104(6)(suppl 3):S268-S277.
3. Sinclair KA, Bogart A, Buchwald D, Henderson JA. The prevalence of metabolic syndrome and associated risk factors in Northern Plains and Southwest American Indians. Diabetes Care. 2011;34(1):118-120.
4. Cobb N, Espey D, King J. Health behaviors and risk factors among American Indians and Alaska Natives, 2000–2010. Am J Public Health. 2014;104(6)(suppl 3):S481-S489.
5. Warne D, Frizzell LB. American Indian health policy: historical trends and contemporary issues. Am J Public Health. 2014;104(6)(suppl 3):S263-S267.
6. Noren J, Kindig D, Sprenger A. Challenges to Native American health care. Public Health Rep. 1998;113(1):22-23.
7. Indian Health Services. Follow Your Path: The Uniformed Services University of the Health Sciences Participant Program Guide. https://www.ihs.gov/careeropps/includes/themes/responsive2017/display_objects/documents/USUHS-IHS-Participant-Program-Guide.pdf. Published October 2015. Accessed August 16, 2018.
8. Starfield B, Shi L, Macinko J. Contribution of primary care to health systems and health. Milbank Q . 2005;83(3):457-502.
9. Health Resources and Services Administration. Projecting the supply and demand for primary care practitioners through 2020. https://bhw.hrsa.gov/health-workforce-analysis/primary-care-2020. Accessed December 14, 2018.
10. Dill MJ, Salsberg ES. The complexities of physician supply and demand: projections through 2025. https://members.aamc.org/eweb/upload/The%20Complexities%20of%20Physician%20Supply.pdf. Published November 2008. Accessed December 14, 2018.
11. Wilson N, Couper I, De Vries E, Reid S, Fish T, Marais B. A critical review of interventions to redress the inequitable distribution of healthcare professionals to rural and remote areas. Rural Remote Health . 2009;9(2):1060.
12. Department of Health and Human Services. Memorandum. Continued PHS Participation at USUHS. https://profiles.nlm.nih.gov/ps/access/QQBBZV.pdf. Published December 11, 1981. Accessed December 14, 2018.
The Uniformed Services University of the Health Sciences (USU) was established by Congress in 1972 under the Uniformed Services Health Professions Revitalization Act. The only medical school administered by the federal government, “America’s Medical School” as it is affectionately known, has a mission to educate, train, and comprehensively prepare uniformed services health professionals to support the US military and public health system.
The USU School of Medicine (SOM) matriculates about 170 students each year. Although the majority of the medical students receive commissions in the US Army, Navy, or Air Force and serve as military physicians in the Department of Defense (DoD), a small number of students each year are commissioned as officers in the US Public Health Service Commissioned Corps (PHS). The PHS is a uniformed service within the US Department of Health and Human Services (HHS) whose officers serve nationwide in more than 30 government agencies. However, unlike its sister DoD services, the PHS does not participate in the Health Professions Scholarship Program, so admission to USU represents the only direct accession to the PHS Commissioned Corps for prospective physicians.
Beginning with the first graduating class, more than 160 PHS physician officers have now been trained under agreements with PHS agencies and SOM, and numerous others have received training and experience from the other academic programs and research centers within USU. Ten of those graduates achieved the rank of Rear Admiral, the general officer or “flag” position of the PHS.
The benefits of the partnerships between USU, PHS, and the agencies served by PHS to public health outcomes are many. Specifically, investment in PHS students at the SOM has served to ease disparities experienced by American Indians and Alaskan Natives (AI/AN), combat the shortage of primary care physicians (PCPs), generate exceptional clinical researchers, and train health care professionals to be prepared and ready to respond to emerging threats to public health.
Addressing Health Care Disparities Experienced by AI/AN
Through numerous treaties, laws, court cases, and Executive Orders—and most recently reaffirmed by the reauthorization of the Indian Health Care Improvement Act as part of the Patient Protection and Affordable Care Act (2010)–the US federal government holds responsibility for the provision of medical services to AI/AN. The Indian Health Service (IHS) is the principal federal provider of health care services for the AI/AN population. The mission of the IHS is to raise the physical, mental, social, and spiritual health of the AI/AN population to the highest level. It seeks to accomplish this mission by assuring that comprehensive, culturally acceptable personal and public health services are available and accessible to all AI/AN people.
Agency partnerships at USU, like the one between the school and IHS, sponsor medical students to become PHS physicians who can combat health disparities, especially those experienced by AI/AN. AI/AN continue to be subjected to disparities in health status across a wide array of chronic conditions, with significantly higher mortality rates than those of white populations.1 These trends are driven by multifactorial etiologies, including social determinants of health,2 obesity and the metabolic syndrome,3 high rates of tobacco and alcohol use,4 and limited access to medical care.5
Recruitment and retention of health care providers (HCPs) has long been a challenge for the IHS.6 Despite many attractive factors, providing care in a setting of otherwise limited resources and the relative remoteness of most facilities may prove to be deterring factors to prospective applicants. Furthermore, promotion of quality providers to administrative roles and high turnover rates of contractors or temporary staff contribute to poor continuity of care in certain locations. Consequently, efforts are under way to increase provider retention and continuity of care for patients.
This effort is augmented by training officers for a career of service to the IHS within the PHS. After completion of medical school and a residency in primary care, IHS-sponsored graduates from USU serve as officers in the PHS, stationed at an IHS-designated high-priority site for 10 years.7 However, many stay with the IHS for much longer, like IHS Chief Medical Officer, RADM Michael Toedt (USU 1995). In fact, nearly all the officers commissioned in the past 20 years are still on active duty. Within the IHS, physicians focus on community-oriented practice and improving the health of small-town and rural residents at tribal or federally operated clinics and community hospitals. In addition to performing clinical duties, graduates frequently become leaders within the IHS, advocating for systemwide improvements, performing practice-based research, and improving the overall well-being of AI/AN communities.
Combating the PCP Shortage
It has been well documented that primary care is essential for the prevention and control of chronic disease.8 However, fewer US medical school graduates are choosing to practice in primary care specialties, and the number of PCPs is forecasted to be insufficient for the needs of the American population in the coming years.9,10 This deficit is predicted to be especially pronounced in rural and underserved communities.11
Training PHS officers at the USU can fill this growing need by cultivating PCPs committed to a career of service in areas of high need. PHS medical students who are sponsored to attend USU by the IHS select from 1 of 7 approved primary care residencies: emergency medicine, family medicine, general pediatrics, general internal medicine, general psychiatry, obstetrics/gynecology, and general surgery.7 PHS students are permitted to train at military or civilian graduate medical education programs; permission to pursue combination programs is granted on a case-by-case basis, with consideration for the needs of the agency. Previously, such authorizations have included internal medicine/pediatrics, internal medicine/psychiatry, and family medicine/preventive medicine. This requirement, understood at the time of matriculation, selects for students who are passionate about primary care and are willing to live and practice in rural, underserved areas during their 10-year service commitment to the agency.
During medical school, USU students participate in numerous training activities that prepare doctors for practice in isolated or resource-poor settings, including point-of-care ultrasonography and field exercises in stabilization and transport of critically ill patients. The motto of the SOM, “Learning to Care for Those in Harm’s Way,” thereby applies not only to battlefield medicine, but to those who practice medicine in austere environments of all kinds.
Generating Clinical Researchers
Although IHS currently funds most PHS students, sponsorship also is available through the National Institute of Allergy and Infectious Diseases (NIAID), one of the institutes of the National Institutes of Health (NIH) in Bethesda, Maryland. Students selected for this competitive program complete a residency in either internal medicine or pediatrics, then complete an NIH-sponsored fellowship in either infectious diseases or allergy and immunology. Similar to their IHS counterparts, they incur a debt of service—10 years in the PHS Commissioned Corps; however, their service obligation is served at NIH. This track supports the creation of the next generation of clinical researchers and physician-scientists, critical in this time of ever-increasing threats to public health and national security, like emerging infectious diseases and bioterrorism.
Emergency Response Preparations
Combined training with experts from DoD and HHS prepares junior medical officers to serve as leaders in responding to large-scale emergencies and disasters. According to a memorandum of December 11, 1981, then Surgeon General C. Everett Koop described the importance of this skill set, saying that USU students are “ready for instant mobilization to meet military [needs] and [respond to] national disasters.” He continued, “Students are taught the necessary leadership and management skills to command medical units and organizations in the delivery of health services...They are exposed to the problems of dealing with national medical emergencies such as floods, earthquakes, and mass immigrations to this country.”12 Fittingly, physician graduates of USU have recently led disaster response efforts for Hurricanes Harvey, Irma, and Maria and Typhoon Yutu.
Traditional medical school didactic coursework is supplemented by lectures on disaster response, emergency preparedness, and global health engagement. As training progresses, students translate their knowledge into action with practical fieldwork exercises in mass casualty triage, erection of field hospitals using preventive medicine principles, and containment of infectious disease outbreaks among displaced persons—under the close observation and guidance of military and public health subject matter experts from across the country. Medical students complete their clinical training at military treatment facilities around the country and have elective clerkship opportunities in operational medicine nationally and internationally. PHS graduates of USU are well prepared to interface with their military colleagues, building effective joint mission capacity.
Additional Training Opportunities
In addition to the 4-year, tuition-free MD program, the university offers 7 graduate degree programs in public health and residency programs in preventive medicine specialty areas. Continuing education opportunities and graduate certificates are available in global health, tropical medicine and hygiene, travelers’ health, international and domestic disaster response, and other fields of interest to any public health professional, military or civilian. Many programs are available to federal or uniformed service members at no cost, some incur a degree of service commitment. Furthermore, the university is home to multiple research centers, including the National Center for Disaster Medicine and Public Health, which strive to improve public health through research efforts and education.
Conclusion
Though the emerging public health needs of the nation are both varied and daunting, the USU/PHS partnership trains providers that will heed the call and face the modern public health needs head-on. USU remains an important source for commissioning PHS physicians and producing career officers. The unique training provided at USU educates and enables PHS physicians to ease disparities experienced by AI/AN, combat the shortage of PCPs, generate exceptional clinical researchers, and be prepared and ready to respond to emerging threats to public health.
The Uniformed Services University of the Health Sciences (USU) was established by Congress in 1972 under the Uniformed Services Health Professions Revitalization Act. The only medical school administered by the federal government, “America’s Medical School” as it is affectionately known, has a mission to educate, train, and comprehensively prepare uniformed services health professionals to support the US military and public health system.
The USU School of Medicine (SOM) matriculates about 170 students each year. Although the majority of the medical students receive commissions in the US Army, Navy, or Air Force and serve as military physicians in the Department of Defense (DoD), a small number of students each year are commissioned as officers in the US Public Health Service Commissioned Corps (PHS). The PHS is a uniformed service within the US Department of Health and Human Services (HHS) whose officers serve nationwide in more than 30 government agencies. However, unlike its sister DoD services, the PHS does not participate in the Health Professions Scholarship Program, so admission to USU represents the only direct accession to the PHS Commissioned Corps for prospective physicians.
Beginning with the first graduating class, more than 160 PHS physician officers have now been trained under agreements with PHS agencies and SOM, and numerous others have received training and experience from the other academic programs and research centers within USU. Ten of those graduates achieved the rank of Rear Admiral, the general officer or “flag” position of the PHS.
The benefits of the partnerships between USU, PHS, and the agencies served by PHS to public health outcomes are many. Specifically, investment in PHS students at the SOM has served to ease disparities experienced by American Indians and Alaskan Natives (AI/AN), combat the shortage of primary care physicians (PCPs), generate exceptional clinical researchers, and train health care professionals to be prepared and ready to respond to emerging threats to public health.
Addressing Health Care Disparities Experienced by AI/AN
Through numerous treaties, laws, court cases, and Executive Orders—and most recently reaffirmed by the reauthorization of the Indian Health Care Improvement Act as part of the Patient Protection and Affordable Care Act (2010)–the US federal government holds responsibility for the provision of medical services to AI/AN. The Indian Health Service (IHS) is the principal federal provider of health care services for the AI/AN population. The mission of the IHS is to raise the physical, mental, social, and spiritual health of the AI/AN population to the highest level. It seeks to accomplish this mission by assuring that comprehensive, culturally acceptable personal and public health services are available and accessible to all AI/AN people.
Agency partnerships at USU, like the one between the school and IHS, sponsor medical students to become PHS physicians who can combat health disparities, especially those experienced by AI/AN. AI/AN continue to be subjected to disparities in health status across a wide array of chronic conditions, with significantly higher mortality rates than those of white populations.1 These trends are driven by multifactorial etiologies, including social determinants of health,2 obesity and the metabolic syndrome,3 high rates of tobacco and alcohol use,4 and limited access to medical care.5
Recruitment and retention of health care providers (HCPs) has long been a challenge for the IHS.6 Despite many attractive factors, providing care in a setting of otherwise limited resources and the relative remoteness of most facilities may prove to be deterring factors to prospective applicants. Furthermore, promotion of quality providers to administrative roles and high turnover rates of contractors or temporary staff contribute to poor continuity of care in certain locations. Consequently, efforts are under way to increase provider retention and continuity of care for patients.
This effort is augmented by training officers for a career of service to the IHS within the PHS. After completion of medical school and a residency in primary care, IHS-sponsored graduates from USU serve as officers in the PHS, stationed at an IHS-designated high-priority site for 10 years.7 However, many stay with the IHS for much longer, like IHS Chief Medical Officer, RADM Michael Toedt (USU 1995). In fact, nearly all the officers commissioned in the past 20 years are still on active duty. Within the IHS, physicians focus on community-oriented practice and improving the health of small-town and rural residents at tribal or federally operated clinics and community hospitals. In addition to performing clinical duties, graduates frequently become leaders within the IHS, advocating for systemwide improvements, performing practice-based research, and improving the overall well-being of AI/AN communities.
Combating the PCP Shortage
It has been well documented that primary care is essential for the prevention and control of chronic disease.8 However, fewer US medical school graduates are choosing to practice in primary care specialties, and the number of PCPs is forecasted to be insufficient for the needs of the American population in the coming years.9,10 This deficit is predicted to be especially pronounced in rural and underserved communities.11
Training PHS officers at the USU can fill this growing need by cultivating PCPs committed to a career of service in areas of high need. PHS medical students who are sponsored to attend USU by the IHS select from 1 of 7 approved primary care residencies: emergency medicine, family medicine, general pediatrics, general internal medicine, general psychiatry, obstetrics/gynecology, and general surgery.7 PHS students are permitted to train at military or civilian graduate medical education programs; permission to pursue combination programs is granted on a case-by-case basis, with consideration for the needs of the agency. Previously, such authorizations have included internal medicine/pediatrics, internal medicine/psychiatry, and family medicine/preventive medicine. This requirement, understood at the time of matriculation, selects for students who are passionate about primary care and are willing to live and practice in rural, underserved areas during their 10-year service commitment to the agency.
During medical school, USU students participate in numerous training activities that prepare doctors for practice in isolated or resource-poor settings, including point-of-care ultrasonography and field exercises in stabilization and transport of critically ill patients. The motto of the SOM, “Learning to Care for Those in Harm’s Way,” thereby applies not only to battlefield medicine, but to those who practice medicine in austere environments of all kinds.
Generating Clinical Researchers
Although IHS currently funds most PHS students, sponsorship also is available through the National Institute of Allergy and Infectious Diseases (NIAID), one of the institutes of the National Institutes of Health (NIH) in Bethesda, Maryland. Students selected for this competitive program complete a residency in either internal medicine or pediatrics, then complete an NIH-sponsored fellowship in either infectious diseases or allergy and immunology. Similar to their IHS counterparts, they incur a debt of service—10 years in the PHS Commissioned Corps; however, their service obligation is served at NIH. This track supports the creation of the next generation of clinical researchers and physician-scientists, critical in this time of ever-increasing threats to public health and national security, like emerging infectious diseases and bioterrorism.
Emergency Response Preparations
Combined training with experts from DoD and HHS prepares junior medical officers to serve as leaders in responding to large-scale emergencies and disasters. According to a memorandum of December 11, 1981, then Surgeon General C. Everett Koop described the importance of this skill set, saying that USU students are “ready for instant mobilization to meet military [needs] and [respond to] national disasters.” He continued, “Students are taught the necessary leadership and management skills to command medical units and organizations in the delivery of health services...They are exposed to the problems of dealing with national medical emergencies such as floods, earthquakes, and mass immigrations to this country.”12 Fittingly, physician graduates of USU have recently led disaster response efforts for Hurricanes Harvey, Irma, and Maria and Typhoon Yutu.
Traditional medical school didactic coursework is supplemented by lectures on disaster response, emergency preparedness, and global health engagement. As training progresses, students translate their knowledge into action with practical fieldwork exercises in mass casualty triage, erection of field hospitals using preventive medicine principles, and containment of infectious disease outbreaks among displaced persons—under the close observation and guidance of military and public health subject matter experts from across the country. Medical students complete their clinical training at military treatment facilities around the country and have elective clerkship opportunities in operational medicine nationally and internationally. PHS graduates of USU are well prepared to interface with their military colleagues, building effective joint mission capacity.
Additional Training Opportunities
In addition to the 4-year, tuition-free MD program, the university offers 7 graduate degree programs in public health and residency programs in preventive medicine specialty areas. Continuing education opportunities and graduate certificates are available in global health, tropical medicine and hygiene, travelers’ health, international and domestic disaster response, and other fields of interest to any public health professional, military or civilian. Many programs are available to federal or uniformed service members at no cost, some incur a degree of service commitment. Furthermore, the university is home to multiple research centers, including the National Center for Disaster Medicine and Public Health, which strive to improve public health through research efforts and education.
Conclusion
Though the emerging public health needs of the nation are both varied and daunting, the USU/PHS partnership trains providers that will heed the call and face the modern public health needs head-on. USU remains an important source for commissioning PHS physicians and producing career officers. The unique training provided at USU educates and enables PHS physicians to ease disparities experienced by AI/AN, combat the shortage of PCPs, generate exceptional clinical researchers, and be prepared and ready to respond to emerging threats to public health.
1. Espey DK, Jim MA, Cobb N, et al. Leading causes of death and all-cause mortality in American Indians and Alaska natives. Am J Public Health . 2014;104(S3):S303-S311.
2. Kunitz SJ, Veazie M, Henderson JA. Historical trends and regional differences in all-cause and amenable mortality among American Indians and Alaska Natives since 1950. Am J Public Health. 2014;104(6)(suppl 3):S268-S277.
3. Sinclair KA, Bogart A, Buchwald D, Henderson JA. The prevalence of metabolic syndrome and associated risk factors in Northern Plains and Southwest American Indians. Diabetes Care. 2011;34(1):118-120.
4. Cobb N, Espey D, King J. Health behaviors and risk factors among American Indians and Alaska Natives, 2000–2010. Am J Public Health. 2014;104(6)(suppl 3):S481-S489.
5. Warne D, Frizzell LB. American Indian health policy: historical trends and contemporary issues. Am J Public Health. 2014;104(6)(suppl 3):S263-S267.
6. Noren J, Kindig D, Sprenger A. Challenges to Native American health care. Public Health Rep. 1998;113(1):22-23.
7. Indian Health Services. Follow Your Path: The Uniformed Services University of the Health Sciences Participant Program Guide. https://www.ihs.gov/careeropps/includes/themes/responsive2017/display_objects/documents/USUHS-IHS-Participant-Program-Guide.pdf. Published October 2015. Accessed August 16, 2018.
8. Starfield B, Shi L, Macinko J. Contribution of primary care to health systems and health. Milbank Q . 2005;83(3):457-502.
9. Health Resources and Services Administration. Projecting the supply and demand for primary care practitioners through 2020. https://bhw.hrsa.gov/health-workforce-analysis/primary-care-2020. Accessed December 14, 2018.
10. Dill MJ, Salsberg ES. The complexities of physician supply and demand: projections through 2025. https://members.aamc.org/eweb/upload/The%20Complexities%20of%20Physician%20Supply.pdf. Published November 2008. Accessed December 14, 2018.
11. Wilson N, Couper I, De Vries E, Reid S, Fish T, Marais B. A critical review of interventions to redress the inequitable distribution of healthcare professionals to rural and remote areas. Rural Remote Health . 2009;9(2):1060.
12. Department of Health and Human Services. Memorandum. Continued PHS Participation at USUHS. https://profiles.nlm.nih.gov/ps/access/QQBBZV.pdf. Published December 11, 1981. Accessed December 14, 2018.
1. Espey DK, Jim MA, Cobb N, et al. Leading causes of death and all-cause mortality in American Indians and Alaska natives. Am J Public Health . 2014;104(S3):S303-S311.
2. Kunitz SJ, Veazie M, Henderson JA. Historical trends and regional differences in all-cause and amenable mortality among American Indians and Alaska Natives since 1950. Am J Public Health. 2014;104(6)(suppl 3):S268-S277.
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