Article

Alcohol use disorder (AUD) is a chronic disease characterized by an impaired ability to control alcohol use that negatively impacts the social, occupational, and health aspects of patients’ lives.¹ It is the third leading modifiable cause of death in the United States.² About 50% of patients with AUD experience alcohol withdrawal syndrome (AWS) following abrupt cessation of alcohol use. AWS often presents with mild symptoms, such as headaches, nausea, vomiting, and anxiety. However, as many as 20% of patients experience severe and potentially life-threatening symptoms, such as tremors, delirium, hallucinations, and seizures within 48 hours of AWS onset.³

Benzodiazepines, such as lorazepam or chlordiazepoxide, are considered the gold standard for AWS.⁴ Benzodiazepines act by potentiation of γ-aminobutyric acid (GABA) receptors that produce inhibitory responses in the central nervous system (CNS). This mechanism is similar to the activity of ethanol, which acts primarily at the GABA-A receptors, resulting in facilitation of GABAergic transmission. The Clinical Institute Withdrawal Assessment (CIWA) of Alcohol scale is a commonly used tool to assess the severity of AWS and the appropriate dosing schedule of benzodiazepines.³ Multiple studies have demonstrated the superiority of using benzodiazepines, as they are beneficial for reducing withdrawal severity and incidence of delirium and seizures.^5,6

Although benzodiazepines are effective, they are associated with serious adverse effects (AEs), such as respiratory depression, excessive sedation, and abuse potential.⁴ Older patients are at higher risk of these AEs, particularly oversedation. In addition, sudden discontinuation of a benzodiazepine treatment can result in anxiety, irritability, and insomnia, which might worsen AWS.

Given the safety concerns of benzodiazepines, alternative treatments for AWS management have been investigated, including gabapentin. Previous studies have demonstrated gabapentin might be effective for mild-to-moderate AWS management.^7-9 Gabapentin exhibits its action by binding to the α2δ subunit of voltage-activated calcium channels with high affinity. Although the exact mechanism of action of gabapentin in AWS is unknown, it has been proposed that gabapentin normalizes GABA activation in the amygdala, which is associated with alcohol dependence.¹⁰ A systemic review conducted by Leung and colleagues found that gabapentin might be an option for the management of mild AWS.¹¹ However, current evidence does not support the use of gabapentin monotherapy in patients with severe AWS, a history of seizures, or those at risk of delirium tremens (DTs) since there is a higher chance of complications.

Baclofen is another medication investigated by researchers for use in patients with AWS. Baclofen works by activating the GABA-B receptor, which results in the downregulation of GABA-A activity. This results in a negative feedback loop leading to a decrease in excitatory neurotransmitters that is similar to the effect produced by alcohol.¹² However, there is limited evidence that baclofen is effective as monotherapy for the treatment of AWS. A Cochrane review previously evaluated baclofen use in AWS but found insufficient evidence of its efficacy and safety for this indication.¹³

Methods

We performed a retrospective cohort chart review at CJALFHCC. Data were collected from the facility’s electronic health record Computerized Patient Record System (CPRS). This study was approved by the Edward Hines Jr. Veterans Affairs Hospital Institutional Review Board.

Patient records were screened and included if they met the following criteria: (1) Patients aged ≥ 18 years who were hospitalized from January 1, 2014, to July 31, 2021, for the primary indication of AWS; (2) Patients who received a g/b or benzodiazepine protocol during AWS hospitalization. If a patient was admitted multiple times for AWS management, only the first admission was included for primary outcome analysis. Exclusion criteria were patients who were active-duty service members, discharged within 24 hours; patients with a primary seizure disorder; patients with known gabapentin, baclofen, or benzodiazepine allergy or intolerance. Patients who used gabapentin, baclofen, or benzodiazepines in an outpatient setting prior to AWS admission; had concurrent intoxication or overdose involving substances other than alcohol; had a concurrent regimen of gabapentin, baclofen, or benzodiazepines; or had initiation on adjuvant medications for AWS management (eg, divalproex, haloperidol, carbamazepine, or clonidine) also were excluded. Patients were categorized as those who received g/b as the initial therapy after admission or patients who received benzodiazepine therapy.

CPRS was used to collect information including baseline demographics, blood alcohol content, CIWA scores throughout hospitalization, number of admissions for alcohol detoxification in the previous year, AWS readmission within 30 days after discharge, prior treatment with g/b, history of alcohol withdrawal seizures and DTs, hospital LOS, outpatient medications for AUD treatment, rates of conversions from g/b protocol to lorazepam, and rates of transition to a higher level of care.

Statistical Analysis

Study data were stored and analyzed using an Excel spreadsheet and IBM SPSS Statistics software. LOS was compared between the g/b and benzodiazepine groups using inferential statistics. An independent 2-sample t test was used to assess the primary outcome if data were normally distributed. If the collected data were not distributed normally, the Mann-Whitney U test was used. All other continuous variables were assessed by using independent t tests and categorical variables by using χ² tests. A P value < .05 was considered statistically significant. Effect size of d = 0.42 was calculated based on a previous study with a similar research design as our study.⁹ We determined that if using an independent 2-sample t test for the primary outcome analysis, an estimated sample size of 178 subjects would provide the study with an 80% power to detect a difference at a 2-sided significance level with α = 0.05. If using the Mann-Whitney U test, 186 subjects would be required to provide identical power.

Results

We reviewed 196 patient health records, and 39 were initially excluded. The most common reason was that AWS was not the primary diagnosis for hospitalization (n = 28).

 

 

Discussion

This retrospective chart review study found that LOS was shorter in patients with AWS treated with g/b compared with those treated with benzodiazepines, with no significant difference in safety outcomes such as seizures, DTs, or intensive care unit transfers. Although there was a statistically significant difference in the primary outcome between the 2 groups, it appears that patients on benzodiazepine therapy originally had more severe AWS presentation as their admission and maximum CIWA scores were statistically significantly higher compared with the g/b group. Thus, patients who were initially started on g/b had less serious AWS presentations. Based on this information we can conclude that the g/b combination may be an effective option for mild AWS management.

To our knowledge, this is the first study that has investigated the combination of g/b compared with benzodiazepines for AWS management in hospitalized patients. The research design of this project was adapted from the Bates and colleagues study that examined gabapentin monotherapy use for the treatment of patients hospitalized with AWS.⁹ We specifically used the primary outcome that they defined in their study since their LOS definition aimed to reflect clinically active withdrawal rather than simply hours of hospitalization, which would decrease the risk of confounding the primary outcome. The results of our research were similar to Bates and colleagues as they found that the gabapentin protocol appeared to be an effective and safe option compared with benzodiazepines for patients hospitalized with AWS.⁹

Limitations

This study has multiple limitations. As it was a retrospective chart review study, the data collection accuracy depends on accurate recordkeeping. Additionally, certain information was missing, such as CIWA scores for some patients. This study has limited external validity as most of the patients were older, White, and male, and the data collection was limited only to a single center. Therefore, it is uncertain whether the results of this study can be generalized to other populations. Also, this study had a small sample size, and we were not able to obtain the intended number of patients to achieve a power of 80%. Lastly, some background characteristics, such as admission and maximum CIWA scores, were not distributed equally between groups. Therefore, future studies are needed with a larger sample size that examine the LOS in the g/b group compared with the benzodiazepine group and in which CIWA scores are matched to reduce the effect of extraneous variables.

Conclusions

Gabapentin and baclofen combination seems to be an effective and safe alternative to benzodiazepines and may be considered for managing mild AWS in hospitalized patients, but additional research is needed to examine this regimen.

Acknowledgments

Research committee: Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, PharmD; Jennifer Kwon, PharmD, BCOP. Co-investigators: Zachary Rosenfeldt, PharmD, BCPS; Kaylee Caniff, PharmD, BCIDP.

Alcohol use disorder (AUD) is a chronic disease characterized by an impaired ability to control alcohol use that negatively impacts the social, occupational, and health aspects of patients’ lives.¹ It is the third leading modifiable cause of death in the United States.² About 50% of patients with AUD experience alcohol withdrawal syndrome (AWS) following abrupt cessation of alcohol use. AWS often presents with mild symptoms, such as headaches, nausea, vomiting, and anxiety. However, as many as 20% of patients experience severe and potentially life-threatening symptoms, such as tremors, delirium, hallucinations, and seizures within 48 hours of AWS onset.³

Benzodiazepines, such as lorazepam or chlordiazepoxide, are considered the gold standard for AWS.⁴ Benzodiazepines act by potentiation of γ-aminobutyric acid (GABA) receptors that produce inhibitory responses in the central nervous system (CNS). This mechanism is similar to the activity of ethanol, which acts primarily at the GABA-A receptors, resulting in facilitation of GABAergic transmission. The Clinical Institute Withdrawal Assessment (CIWA) of Alcohol scale is a commonly used tool to assess the severity of AWS and the appropriate dosing schedule of benzodiazepines.³ Multiple studies have demonstrated the superiority of using benzodiazepines, as they are beneficial for reducing withdrawal severity and incidence of delirium and seizures.^5,6

Although benzodiazepines are effective, they are associated with serious adverse effects (AEs), such as respiratory depression, excessive sedation, and abuse potential.⁴ Older patients are at higher risk of these AEs, particularly oversedation. In addition, sudden discontinuation of a benzodiazepine treatment can result in anxiety, irritability, and insomnia, which might worsen AWS.

Given the safety concerns of benzodiazepines, alternative treatments for AWS management have been investigated, including gabapentin. Previous studies have demonstrated gabapentin might be effective for mild-to-moderate AWS management.^7-9 Gabapentin exhibits its action by binding to the α2δ subunit of voltage-activated calcium channels with high affinity. Although the exact mechanism of action of gabapentin in AWS is unknown, it has been proposed that gabapentin normalizes GABA activation in the amygdala, which is associated with alcohol dependence.¹⁰ A systemic review conducted by Leung and colleagues found that gabapentin might be an option for the management of mild AWS.¹¹ However, current evidence does not support the use of gabapentin monotherapy in patients with severe AWS, a history of seizures, or those at risk of delirium tremens (DTs) since there is a higher chance of complications.

Baclofen is another medication investigated by researchers for use in patients with AWS. Baclofen works by activating the GABA-B receptor, which results in the downregulation of GABA-A activity. This results in a negative feedback loop leading to a decrease in excitatory neurotransmitters that is similar to the effect produced by alcohol.¹² However, there is limited evidence that baclofen is effective as monotherapy for the treatment of AWS. A Cochrane review previously evaluated baclofen use in AWS but found insufficient evidence of its efficacy and safety for this indication.¹³

Methods

We performed a retrospective cohort chart review at CJALFHCC. Data were collected from the facility’s electronic health record Computerized Patient Record System (CPRS). This study was approved by the Edward Hines Jr. Veterans Affairs Hospital Institutional Review Board.

Patient records were screened and included if they met the following criteria: (1) Patients aged ≥ 18 years who were hospitalized from January 1, 2014, to July 31, 2021, for the primary indication of AWS; (2) Patients who received a g/b or benzodiazepine protocol during AWS hospitalization. If a patient was admitted multiple times for AWS management, only the first admission was included for primary outcome analysis. Exclusion criteria were patients who were active-duty service members, discharged within 24 hours; patients with a primary seizure disorder; patients with known gabapentin, baclofen, or benzodiazepine allergy or intolerance. Patients who used gabapentin, baclofen, or benzodiazepines in an outpatient setting prior to AWS admission; had concurrent intoxication or overdose involving substances other than alcohol; had a concurrent regimen of gabapentin, baclofen, or benzodiazepines; or had initiation on adjuvant medications for AWS management (eg, divalproex, haloperidol, carbamazepine, or clonidine) also were excluded. Patients were categorized as those who received g/b as the initial therapy after admission or patients who received benzodiazepine therapy.

CPRS was used to collect information including baseline demographics, blood alcohol content, CIWA scores throughout hospitalization, number of admissions for alcohol detoxification in the previous year, AWS readmission within 30 days after discharge, prior treatment with g/b, history of alcohol withdrawal seizures and DTs, hospital LOS, outpatient medications for AUD treatment, rates of conversions from g/b protocol to lorazepam, and rates of transition to a higher level of care.

Statistical Analysis

Study data were stored and analyzed using an Excel spreadsheet and IBM SPSS Statistics software. LOS was compared between the g/b and benzodiazepine groups using inferential statistics. An independent 2-sample t test was used to assess the primary outcome if data were normally distributed. If the collected data were not distributed normally, the Mann-Whitney U test was used. All other continuous variables were assessed by using independent t tests and categorical variables by using χ² tests. A P value < .05 was considered statistically significant. Effect size of d = 0.42 was calculated based on a previous study with a similar research design as our study.⁹ We determined that if using an independent 2-sample t test for the primary outcome analysis, an estimated sample size of 178 subjects would provide the study with an 80% power to detect a difference at a 2-sided significance level with α = 0.05. If using the Mann-Whitney U test, 186 subjects would be required to provide identical power.

Results

We reviewed 196 patient health records, and 39 were initially excluded. The most common reason was that AWS was not the primary diagnosis for hospitalization (n = 28).

 

 

Discussion

This retrospective chart review study found that LOS was shorter in patients with AWS treated with g/b compared with those treated with benzodiazepines, with no significant difference in safety outcomes such as seizures, DTs, or intensive care unit transfers. Although there was a statistically significant difference in the primary outcome between the 2 groups, it appears that patients on benzodiazepine therapy originally had more severe AWS presentation as their admission and maximum CIWA scores were statistically significantly higher compared with the g/b group. Thus, patients who were initially started on g/b had less serious AWS presentations. Based on this information we can conclude that the g/b combination may be an effective option for mild AWS management.

To our knowledge, this is the first study that has investigated the combination of g/b compared with benzodiazepines for AWS management in hospitalized patients. The research design of this project was adapted from the Bates and colleagues study that examined gabapentin monotherapy use for the treatment of patients hospitalized with AWS.⁹ We specifically used the primary outcome that they defined in their study since their LOS definition aimed to reflect clinically active withdrawal rather than simply hours of hospitalization, which would decrease the risk of confounding the primary outcome. The results of our research were similar to Bates and colleagues as they found that the gabapentin protocol appeared to be an effective and safe option compared with benzodiazepines for patients hospitalized with AWS.⁹

Limitations

This study has multiple limitations. As it was a retrospective chart review study, the data collection accuracy depends on accurate recordkeeping. Additionally, certain information was missing, such as CIWA scores for some patients. This study has limited external validity as most of the patients were older, White, and male, and the data collection was limited only to a single center. Therefore, it is uncertain whether the results of this study can be generalized to other populations. Also, this study had a small sample size, and we were not able to obtain the intended number of patients to achieve a power of 80%. Lastly, some background characteristics, such as admission and maximum CIWA scores, were not distributed equally between groups. Therefore, future studies are needed with a larger sample size that examine the LOS in the g/b group compared with the benzodiazepine group and in which CIWA scores are matched to reduce the effect of extraneous variables.

Conclusions

Gabapentin and baclofen combination seems to be an effective and safe alternative to benzodiazepines and may be considered for managing mild AWS in hospitalized patients, but additional research is needed to examine this regimen.

Acknowledgments

Research committee: Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, PharmD; Jennifer Kwon, PharmD, BCOP. Co-investigators: Zachary Rosenfeldt, PharmD, BCPS; Kaylee Caniff, PharmD, BCIDP.

Alcohol use disorder (AUD) is a chronic disease characterized by an impaired ability to control alcohol use that negatively impacts the social, occupational, and health aspects of patients’ lives.¹ It is the third leading modifiable cause of death in the United States.² About 50% of patients with AUD experience alcohol withdrawal syndrome (AWS) following abrupt cessation of alcohol use. AWS often presents with mild symptoms, such as headaches, nausea, vomiting, and anxiety. However, as many as 20% of patients experience severe and potentially life-threatening symptoms, such as tremors, delirium, hallucinations, and seizures within 48 hours of AWS onset.³

Benzodiazepines, such as lorazepam or chlordiazepoxide, are considered the gold standard for AWS.⁴ Benzodiazepines act by potentiation of γ-aminobutyric acid (GABA) receptors that produce inhibitory responses in the central nervous system (CNS). This mechanism is similar to the activity of ethanol, which acts primarily at the GABA-A receptors, resulting in facilitation of GABAergic transmission. The Clinical Institute Withdrawal Assessment (CIWA) of Alcohol scale is a commonly used tool to assess the severity of AWS and the appropriate dosing schedule of benzodiazepines.³ Multiple studies have demonstrated the superiority of using benzodiazepines, as they are beneficial for reducing withdrawal severity and incidence of delirium and seizures.^5,6

Although benzodiazepines are effective, they are associated with serious adverse effects (AEs), such as respiratory depression, excessive sedation, and abuse potential.⁴ Older patients are at higher risk of these AEs, particularly oversedation. In addition, sudden discontinuation of a benzodiazepine treatment can result in anxiety, irritability, and insomnia, which might worsen AWS.

Given the safety concerns of benzodiazepines, alternative treatments for AWS management have been investigated, including gabapentin. Previous studies have demonstrated gabapentin might be effective for mild-to-moderate AWS management.^7-9 Gabapentin exhibits its action by binding to the α2δ subunit of voltage-activated calcium channels with high affinity. Although the exact mechanism of action of gabapentin in AWS is unknown, it has been proposed that gabapentin normalizes GABA activation in the amygdala, which is associated with alcohol dependence.¹⁰ A systemic review conducted by Leung and colleagues found that gabapentin might be an option for the management of mild AWS.¹¹ However, current evidence does not support the use of gabapentin monotherapy in patients with severe AWS, a history of seizures, or those at risk of delirium tremens (DTs) since there is a higher chance of complications.

Baclofen is another medication investigated by researchers for use in patients with AWS. Baclofen works by activating the GABA-B receptor, which results in the downregulation of GABA-A activity. This results in a negative feedback loop leading to a decrease in excitatory neurotransmitters that is similar to the effect produced by alcohol.¹² However, there is limited evidence that baclofen is effective as monotherapy for the treatment of AWS. A Cochrane review previously evaluated baclofen use in AWS but found insufficient evidence of its efficacy and safety for this indication.¹³

Methods

We performed a retrospective cohort chart review at CJALFHCC. Data were collected from the facility’s electronic health record Computerized Patient Record System (CPRS). This study was approved by the Edward Hines Jr. Veterans Affairs Hospital Institutional Review Board.

Patient records were screened and included if they met the following criteria: (1) Patients aged ≥ 18 years who were hospitalized from January 1, 2014, to July 31, 2021, for the primary indication of AWS; (2) Patients who received a g/b or benzodiazepine protocol during AWS hospitalization. If a patient was admitted multiple times for AWS management, only the first admission was included for primary outcome analysis. Exclusion criteria were patients who were active-duty service members, discharged within 24 hours; patients with a primary seizure disorder; patients with known gabapentin, baclofen, or benzodiazepine allergy or intolerance. Patients who used gabapentin, baclofen, or benzodiazepines in an outpatient setting prior to AWS admission; had concurrent intoxication or overdose involving substances other than alcohol; had a concurrent regimen of gabapentin, baclofen, or benzodiazepines; or had initiation on adjuvant medications for AWS management (eg, divalproex, haloperidol, carbamazepine, or clonidine) also were excluded. Patients were categorized as those who received g/b as the initial therapy after admission or patients who received benzodiazepine therapy.

CPRS was used to collect information including baseline demographics, blood alcohol content, CIWA scores throughout hospitalization, number of admissions for alcohol detoxification in the previous year, AWS readmission within 30 days after discharge, prior treatment with g/b, history of alcohol withdrawal seizures and DTs, hospital LOS, outpatient medications for AUD treatment, rates of conversions from g/b protocol to lorazepam, and rates of transition to a higher level of care.

Statistical Analysis

Study data were stored and analyzed using an Excel spreadsheet and IBM SPSS Statistics software. LOS was compared between the g/b and benzodiazepine groups using inferential statistics. An independent 2-sample t test was used to assess the primary outcome if data were normally distributed. If the collected data were not distributed normally, the Mann-Whitney U test was used. All other continuous variables were assessed by using independent t tests and categorical variables by using χ² tests. A P value < .05 was considered statistically significant. Effect size of d = 0.42 was calculated based on a previous study with a similar research design as our study.⁹ We determined that if using an independent 2-sample t test for the primary outcome analysis, an estimated sample size of 178 subjects would provide the study with an 80% power to detect a difference at a 2-sided significance level with α = 0.05. If using the Mann-Whitney U test, 186 subjects would be required to provide identical power.

Results

We reviewed 196 patient health records, and 39 were initially excluded. The most common reason was that AWS was not the primary diagnosis for hospitalization (n = 28).

 

 

Discussion

This retrospective chart review study found that LOS was shorter in patients with AWS treated with g/b compared with those treated with benzodiazepines, with no significant difference in safety outcomes such as seizures, DTs, or intensive care unit transfers. Although there was a statistically significant difference in the primary outcome between the 2 groups, it appears that patients on benzodiazepine therapy originally had more severe AWS presentation as their admission and maximum CIWA scores were statistically significantly higher compared with the g/b group. Thus, patients who were initially started on g/b had less serious AWS presentations. Based on this information we can conclude that the g/b combination may be an effective option for mild AWS management.

To our knowledge, this is the first study that has investigated the combination of g/b compared with benzodiazepines for AWS management in hospitalized patients. The research design of this project was adapted from the Bates and colleagues study that examined gabapentin monotherapy use for the treatment of patients hospitalized with AWS.⁹ We specifically used the primary outcome that they defined in their study since their LOS definition aimed to reflect clinically active withdrawal rather than simply hours of hospitalization, which would decrease the risk of confounding the primary outcome. The results of our research were similar to Bates and colleagues as they found that the gabapentin protocol appeared to be an effective and safe option compared with benzodiazepines for patients hospitalized with AWS.⁹

Limitations

This study has multiple limitations. As it was a retrospective chart review study, the data collection accuracy depends on accurate recordkeeping. Additionally, certain information was missing, such as CIWA scores for some patients. This study has limited external validity as most of the patients were older, White, and male, and the data collection was limited only to a single center. Therefore, it is uncertain whether the results of this study can be generalized to other populations. Also, this study had a small sample size, and we were not able to obtain the intended number of patients to achieve a power of 80%. Lastly, some background characteristics, such as admission and maximum CIWA scores, were not distributed equally between groups. Therefore, future studies are needed with a larger sample size that examine the LOS in the g/b group compared with the benzodiazepine group and in which CIWA scores are matched to reduce the effect of extraneous variables.

Conclusions

Gabapentin and baclofen combination seems to be an effective and safe alternative to benzodiazepines and may be considered for managing mild AWS in hospitalized patients, but additional research is needed to examine this regimen.

Acknowledgments

Research committee: Hong-Yen Vi, PharmD, BCPS; Shaiza Khan, PharmD, BCPS; Yinka Alaka, PharmD; Jennifer Kwon, PharmD, BCOP. Co-investigators: Zachary Rosenfeldt, PharmD, BCPS; Kaylee Caniff, PharmD, BCIDP.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

Acute pain is a primary symptom for many patients who present to the emergency department (ED). The ED team is challenged with relieving pain while limiting harm from medications.¹ A 2017 National Health Interview Survey showed that compared with nonveterans, more veterans reported pain in the previous 3 months, and the rate of severe pain was 40% higher in the veteran group especially among those who served during the era of wars in Afghanistan and Iraq.²

The American College of Emergency Physicians guidelines pain management guidelines recommend patient-centered shared decision making that includes patient education about treatment goals and expectations, and short- and long-term risks, as well as a preference toward pharmacologic treatment with nonopioid analgesics except for patients with severe pain or pain refractory to other drug and treatment modalities.³ There is a lack of evidence regarding superior efficacy of either opioid or nonopioid analgesics; therefore, the use of nonopioid analgesics, such as oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) or central analgesics, such as acetaminophen, is preferred for treating acute pain to mitigate adverse effects (AEs) and risks associated with opioid use.^1,3,4 The US Department of Veterans Affairs (VA) and Department of Defense (DoD) guideline on managing opioid therapy for chronic pain, updated in 2017 and 2022, similarly recommends alternatives to opioids for mild-to-moderate acute pain and encourages multimodal pain care.⁵ However, use of other pharmacologic treatments, such as NSAIDs, is limited by AE profiles, patient contraindications, and severity of acute pain etiologies. There is a need for the expanded use of nonpharmacologic treatments for addressing pain in the veteran population.

The American College of Emergency Physicians guidelines recommend nonpharmacologic modalities, such as applying heat or cold, physical therapy, cognitive behavioral therapy, and acupuncture.³ A 2014 study reported that 37% to 46% of active duty and reserve military personnel use complementary and alternative medicine (CAM) for a variety of ailments, and there is increasing interest in the use of CAM as adjuncts to traditional therapies.⁶ According to one study, some CAM therapies are used significantly more by military personnel than used by civilians.⁷ However, the percentage of the veteran population using acupuncture in this study was small, and more information is needed to assess its use.

Auricular acupuncture originated in traditional Chinese medicine.⁸ Contemporary auricular acupuncture experts view this modality as a self-contained microsystem mapping portions of the ear to specific parts of the body and internal organs. The analgesic effects may be mediated through the central nervous system by local release of endorphins through nerve fiber activation and neurotransmitters—including serotonin, dopamine, and norepinephrine—leading to pre- and postsynaptic suppression of pain transmission.

Battlefield acupuncture (BFA) uses 5 set points anatomically located on each ear.⁹ Practitioners use small semipermanent, dartlike acupuncture needles. Patients could experience pain relief in a few minutes, which can last minutes, hours, days, weeks, or months depending on the pathology of the pain. This procedure developed in 2001 has been studied for different pain types and has shown benefit when used for postsurgical pain, chronic spinal cord injury−related neuropathic pain, and general chronic pain, as well as for other indications, such as insomnia, depression, and weight loss.^8,10-13 In 2018, a randomized controlled trial compared postintervention numeric rating scale (NRS) pain scores in patients presenting to the ED with acute or acute-on-chronic lower back pain who received BFA as an adjunct to standard care vs standard care alone.¹⁴ Patients receiving BFA as an adjunct to standard care were found to have mean postintervention pain scores 1.7 points lower than those receiving standard care alone. This study demonstrated that BFA was feasible and well tolerated for lower back pain in the ED as an adjunct to standard care. The study was limited by the adjunct use of BFA rather than as monotherapy and by the practitioners’ discretion regarding standard care, which was not defined by the study’s authors.

The Jesse Brown Veterans Affairs Medical Center (JBVAMC) in Chicago, Illinois, offers several CAM modalities, such as exercise/movement therapy, chiropractic, art/music therapy, and relaxation workshops, which are widely used by veterans. Recent evidence suggests BFA could reduce pain scores as an adjunct or an alternative to pharmacologic therapy. We are interested in how CAM therapies, such as BFA, can help avoid AEs associated with opioid or NSAID therapy.

At the JBVAMC ED, ketorolac 15 mg is the preferred first-line treatment of acute, noncancer pain, based on the results of previous studies. In 2018 BFA was offered first to veterans presenting with acute or acute-on-chronic pain to the ED; however, its effectiveness for pain reduction vs ketorolac has not been evaluated in this patient population. Limited literature is available on BFA and its use in the ED. To our knowledge, this was the first observational study assessing the difference between a single session of BFA vs a single dose of ketorolac in treating noncancer acute or acute-on-chronic pain in the ED.

Methods

This study was a retrospective chart review of patients who presented to the JBVAMC ED with acute pain or acute-on-chronic pain, who received ketorolac or BFA. The study population was generated from a list of all IV and intramuscular (IM) ketorolac unit dose orders verified from June 1, 2018, through August 30, 2019, and a list of all BFA procedure notes signed from June 1, 2018, through August 30, 2019. Patients were included in the study if they had documented administration of IV or IM ketorolac or BFA between June 1, 2018, and August 30, 2019. Patients who received ketorolac doses other than 15 mg, the intervention was administered outside of the ED, received adjunct treatment in addition to the treatment intervention in the ED, had no baseline NRS pain score documented before the intervention, had an NRS pain score of < 4, had no postintervention NRS pain score documented within 6 hours, had a treatment indication other than pain, or had active cancer were excluded. As in previous JBVAMC studies, we used NRS pain score cutoffs (mild, moderate, severe, and very severe) based on Woo and colleagues’ meta-analysis and excluded scores < 4.¹⁵

Endpoints

The primary endpoint was the mean difference in NRS pain score before and after the intervention, determined by comparing the NRS pain score documented at triage to the ED with the first documented NRS pain score at least 30 minutes to 6 hours after treatment administration. The secondary endpoints included the number of patients prescribed pain medication at discharge, the number of patients who were discharged with no medications, and the number of patients admitted to the hospital. The safety endpoint included any AEs of the intervention. Subgroup analyses were performed comparing the mean difference in NRS pain score among subgroups classified by severity of baseline NRS pain score and pain location.

Statistical Analysis

Baseline characteristics and endpoints were analyzed using descriptive statistics. Categorical data were analyzed using Fisher exact test and z test for proportions, and continuous data were compared using t test and paired t test. An 80% power calculation determined that 84 patients per group were needed to detect a statistically significant difference in pain score reduction of 1.3 at a type-1 error rate of 0.05. The sample size was based on a calculation performed in a previously published study that compared IV ketorolac at 3 single-dose regimens for treating acute pain in the ED.¹⁶ The 1.3 pain score reduction is considered the minimum clinically significant difference in pain that could be detected with the NRS.¹⁷

Results

Sixty-one patients received BFA during the study period: 31 were excluded (26 received adjunct treatment in the ED, 2 had active cancer documented, 2 had an indication other than pain, and 1 received BFA outside of the ED), leaving 30 patients in the BFA cohort. During the study period, 1299 patients received ketorolac. These patients were selected using a random number generator and then screened to determine inclusion or exclusion in the study. We continued to randomly select patients for the ketorolac group until we had a similar number in each treatment group. Of these 148 patients who were randomly selected to be reviewed, 116 were excluded: 48 received adjunct treatment in the ED, 24 had no postintervention NRS pain score documented within 6 hours, 18 received ketorolac doses other than 15 mg, 12 received ketorolac outside the ED, 9 had no baseline NRS pain score documented, 3 presented with a NRS pain score of ≤ 3, and 2 had active cancer documented. The ketorolac cohort comprised 31 patients.

Baseline characteristics were similar between the 2 groups except for the average baseline NRS pain score, which was statistically significantly higher in the BFA vs ketorolac group (8.7 vs 7.7, respectively; P = .02). The mean age was 51 years in the BFA group and 48 years in the ketorolac group. Most patients in each cohort were male: 80% in the BFA group and 71% in the ketorolac group. The most common types of pain documented as the chief ED presentation included back, lower extremity, and head.

Endpoints

The mean difference in NRS pain score was 3.9 for the BFA group and 5.1 for the ketorolac group. Both were clinically and statistically significant reductions (P = .03 and P < .01), but the difference between the intervention groups in NRS score reduction was not statistically significant (P = .07).

For the secondary endpoint of outpatient prescriptions written at discharge, there was no significant difference between the groups except for oral NSAIDs, which were more likely to be prescribed to patients who received ketorolac (P = .01).

Subgroup Analysis

An analysis was performed for subgroups classified by baseline NRS pain score (mild: 4; moderate, 5 - 6; severe, 7 - 9; and very severe, 10). Data for mild pain was limited because a small number of patients received interventions. For moderate pain, the mean difference in NRS pain score for BFA and ketorolac was 3.5 and 3.8, respectively; for severe pain, 3.4 and 5.3; and for very severe pain, 4.6 and 6.4. There was a larger difference in the preintervention and postintervention NRS pain scores within severe pain and very severe pain groups.

Discussion

Both interventions resulted in a significant reduction in the mean NRS pain score of about 4 to 5 points within their group, and BFA resulted in a similar NRS pain score reduction compared with ketorolac 15 mg. Because the baseline NRS pain scores were significantly different between the BFA and ketorolac groups, a subgroup analysis revealed that BFA reduced mean NRS pain score in patients with severe and very severe pain but appears to be less beneficial for moderate pain, unlike the ketorolac results that showed a large reduction in all pain groups except for the small sample of patients with mild pain.

In this study, more patients in the BFA group presented to the ED with lower extremity pain, such as gout or neuropathy, compared with the ketorolac group; however, BFA did not result in a significantly different pain score reduction in this subgroup compared with ketorolac. Patients receiving BFA were more likely to receive topical analgesics or muscle relaxants at discharge; whereas those receiving ketorolac were significantly more likely to receive oral NSAIDs. Patients in this study also were more likely to be admitted to the hospital if they received ketorolac; however, for these patients, pain was secondary to their chief presentation, and the admitting physician’s familiarity with ketorolac might have been the reason for choosing this intervention. Reasons for the admissions were surgical observation, psychiatric stabilization, kidney/gallstones, rule out of acute coronary syndrome, pneumonia, and proctitis in the ketorolac group, and suicidal ideations in the BFA group.

Limitations

As a limited number of patients received BFA at JBVAMC, the study was not sufficiently powered to detect a difference in the primary outcome. Because BFA required a consultation to be entered in the electronic health record, in addition to time needed to perform the procedure, practitioners might have preferred IV/IM ketorolac during busy times in the ED, potentially leading to underrepresentation in the BFA group. Prescribing preferences might have differed among the rotating physicians, timing of the documentation of the NRS pain score could have differed based on the treatment intervention, and the investigators were unable to control or accurately assess whether patients had taken an analgesic medication before presenting to the ED. Because pain and the treating physician are subjective, patients who reported a higher baseline pain severity might have been more likely to be discharged with topical analgesics or muscle relaxants. One way to correct for this subjectivity would be to conduct a larger prospective trial with a single treating physician. Finally, ED encounters in this study were short, and there was no follow-up permitting identification of AEs.

Conclusions

NRS pain score reduction with BFA did not differ compared with ketorolac 15 mg for treating acute and acute-on-chronic pain in the ED. Although this study was underpowered, these results add to the limited existing literature, suggesting that both interventions could result in clinically significant pain score reductions for patients presenting to the ED with severe and very severe pain, making BFA a viable nonpharmacologic option. Future studies could include investigating the benefit of BFA in the veteran population by studying larger samples in the ED, surveying patients after their interventions to identify rates AEs, and exploring the use of BFA for chronic pain in the outpatient setting.

Staphylococcus lugdunensis (S lugdunensis) is a species of coagulase-negative Staphylococcus (CoNS) and a constituent of human skin flora. Unlike other strains of CoNS, however, S lugdunensis has gained notoriety for virulence that resembles Staphylococcus aureus (S aureus). S lugdunensis is now recognized as an important nosocomial pathogen and cause of prosthetic device infections, including vascular catheter infections. We present a case of persistent S lugdunensis bacteremia occurring in a patient on hemodialysis (HD) without any implanted prosthetic materials.

Case Presentation

A 60-year-old man with a history of uncontrolled type 2 diabetes mellitus (T2DM) and end-stage renal disease on home HD via arteriovenous fistula (AVF) presented to the emergency department (ED) for evaluation of subacute progressive low back pain. His symptoms began abruptly 2 weeks prior to presentation without any identifiable trigger or trauma. His pain localized to the lower thoracic spine, radiating anteriorly into his abdomen. He reported tactile fever for several days before presentation but no chills, night sweats, paresthesia, weakness, or bowel/bladder incontinence. He had no recent surgeries, implanted hardware, or invasive procedures involving the spine. HD was performed 5 times a week at home with a family member cannulating his AVF via buttonhole technique. He initially sought evaluation in a community hospital several days prior, where he underwent magnetic resonance imaging (MRI) of the thoracic spine. He was discharged from the community ED with oral opioids prior to the MRI results. He presented to West Los Angeles Veterans Affairs Medical Center (WLAVAMC) ED when MRI results came back indicating abnormalities and he reported recalcitrant pain.

On arrival at WLAVAMC, the patient was afebrile with a heart rate of 107 bpm and blood pressure of 152/97 mm Hg. The remainder of his vital signs were normal. The physical examination revealed midline tenderness on palpation of the distal thoracic and proximal lumbar spine. Muscle strength was 4 of 5 in the bilateral hip flexors, though this was limited by pain. The remainder of his neurologic examination was nonfocal. The cardiac examination was unremarkable with no murmurs auscultated. His left upper extremity AVF had an audible bruit and palpable thrill. The skin examination was notable for acanthosis nigricans but no areas of skin erythema or induration and no obvious stigmata of infective endocarditis.

The initial laboratory workup was remarkable for a white blood cell (WBC) count of 10.0 × 10³/µL with left shift, blood urea nitrogen level of 59 mg/dL, and creatinine level of 9.3 mg/dL. The patient’s erythrocyte sedimentation rate (ESR) was 45 mm/h (reference range, ≤ 20 mm/h) and C-reactive protein level was > 8.0 mg/L (reference range, ≤ 0.74 mg/L). Two months prior the hemoglobin A_1c had been recorded at 9.9%.

Given his intractable low back pain and elevated inflammatory markers, the patient underwent an MRI of the thoracic and lumbar spine with contrast while in the ED. This MRI revealed abnormal marrow edema in the T11-T12 vertebrae with abnormal fluid signal in the T11-T12 disc space. Subjacent paravertebral edema also was noted. There was no well-defined fluid collection or abnormal signal in the spinal cord. Taken together, these findings were concerning for T11-T12 discitis with osteomyelitis.

Discussion

CoNS are a major contributor to human skin flora, a common contaminant of blood cultures, and an important cause of nosocomial bloodstream infections.^1,2 These species have a predilection for forming biofilms, making CoNS a major cause of prosthetic device infections.³ S lugdunensis is a CoNS species that was first described in 1988.⁴ In addition to foreign body–related infections, S lugdunensis has been implicated in bone/joint infections, native valve endocarditis, toxic shock syndrome, and brain abscesses.^5-8 Infections due to S lugdunensis are notorious for their aggressive and fulminant courses. With its increased virulence that is atypical of other CoNS, S lugdunensis has understandably been likened more to S aureus.

Prior cases have been reported of S lugdunensis bacteremia in patients using HD. However, the suspected source of bacteremia in these cases has generally been central venous catheters.^9-12

Conclusions

S lugdunensis is an increasingly recognized cause of nosocomial bloodstream infections. Given the commonalities in virulence that S lugdunensis shares with S aureus, treatment of bacteremia caused by either species should follow similar management principles: prompt initiation of IV antistaphylococcal therapy, a thorough evaluation for the source(s) of bacteremia as well as metastatic complications, and consultation with an infectious disease specialist. This case report also highlights the importance of considering a patient’s AVF as a potential source for infection even in the absence of localized signs of infection. The buttonhole method of AVF cannulation was thought to be a major contributor to the development and persistence of our patient’s bacteremia. This risk should be discussed with patients using a shared decision-making approach when developing a dialysis treatment plan.

Staphylococcus lugdunensis (S lugdunensis) is a species of coagulase-negative Staphylococcus (CoNS) and a constituent of human skin flora. Unlike other strains of CoNS, however, S lugdunensis has gained notoriety for virulence that resembles Staphylococcus aureus (S aureus). S lugdunensis is now recognized as an important nosocomial pathogen and cause of prosthetic device infections, including vascular catheter infections. We present a case of persistent S lugdunensis bacteremia occurring in a patient on hemodialysis (HD) without any implanted prosthetic materials.

Case Presentation

A 60-year-old man with a history of uncontrolled type 2 diabetes mellitus (T2DM) and end-stage renal disease on home HD via arteriovenous fistula (AVF) presented to the emergency department (ED) for evaluation of subacute progressive low back pain. His symptoms began abruptly 2 weeks prior to presentation without any identifiable trigger or trauma. His pain localized to the lower thoracic spine, radiating anteriorly into his abdomen. He reported tactile fever for several days before presentation but no chills, night sweats, paresthesia, weakness, or bowel/bladder incontinence. He had no recent surgeries, implanted hardware, or invasive procedures involving the spine. HD was performed 5 times a week at home with a family member cannulating his AVF via buttonhole technique. He initially sought evaluation in a community hospital several days prior, where he underwent magnetic resonance imaging (MRI) of the thoracic spine. He was discharged from the community ED with oral opioids prior to the MRI results. He presented to West Los Angeles Veterans Affairs Medical Center (WLAVAMC) ED when MRI results came back indicating abnormalities and he reported recalcitrant pain.

On arrival at WLAVAMC, the patient was afebrile with a heart rate of 107 bpm and blood pressure of 152/97 mm Hg. The remainder of his vital signs were normal. The physical examination revealed midline tenderness on palpation of the distal thoracic and proximal lumbar spine. Muscle strength was 4 of 5 in the bilateral hip flexors, though this was limited by pain. The remainder of his neurologic examination was nonfocal. The cardiac examination was unremarkable with no murmurs auscultated. His left upper extremity AVF had an audible bruit and palpable thrill. The skin examination was notable for acanthosis nigricans but no areas of skin erythema or induration and no obvious stigmata of infective endocarditis.

The initial laboratory workup was remarkable for a white blood cell (WBC) count of 10.0 × 10³/µL with left shift, blood urea nitrogen level of 59 mg/dL, and creatinine level of 9.3 mg/dL. The patient’s erythrocyte sedimentation rate (ESR) was 45 mm/h (reference range, ≤ 20 mm/h) and C-reactive protein level was > 8.0 mg/L (reference range, ≤ 0.74 mg/L). Two months prior the hemoglobin A_1c had been recorded at 9.9%.

Given his intractable low back pain and elevated inflammatory markers, the patient underwent an MRI of the thoracic and lumbar spine with contrast while in the ED. This MRI revealed abnormal marrow edema in the T11-T12 vertebrae with abnormal fluid signal in the T11-T12 disc space. Subjacent paravertebral edema also was noted. There was no well-defined fluid collection or abnormal signal in the spinal cord. Taken together, these findings were concerning for T11-T12 discitis with osteomyelitis.

Discussion

CoNS are a major contributor to human skin flora, a common contaminant of blood cultures, and an important cause of nosocomial bloodstream infections.^1,2 These species have a predilection for forming biofilms, making CoNS a major cause of prosthetic device infections.³ S lugdunensis is a CoNS species that was first described in 1988.⁴ In addition to foreign body–related infections, S lugdunensis has been implicated in bone/joint infections, native valve endocarditis, toxic shock syndrome, and brain abscesses.^5-8 Infections due to S lugdunensis are notorious for their aggressive and fulminant courses. With its increased virulence that is atypical of other CoNS, S lugdunensis has understandably been likened more to S aureus.

Prior cases have been reported of S lugdunensis bacteremia in patients using HD. However, the suspected source of bacteremia in these cases has generally been central venous catheters.^9-12

Conclusions

S lugdunensis is an increasingly recognized cause of nosocomial bloodstream infections. Given the commonalities in virulence that S lugdunensis shares with S aureus, treatment of bacteremia caused by either species should follow similar management principles: prompt initiation of IV antistaphylococcal therapy, a thorough evaluation for the source(s) of bacteremia as well as metastatic complications, and consultation with an infectious disease specialist. This case report also highlights the importance of considering a patient’s AVF as a potential source for infection even in the absence of localized signs of infection. The buttonhole method of AVF cannulation was thought to be a major contributor to the development and persistence of our patient’s bacteremia. This risk should be discussed with patients using a shared decision-making approach when developing a dialysis treatment plan.

Staphylococcus lugdunensis (S lugdunensis) is a species of coagulase-negative Staphylococcus (CoNS) and a constituent of human skin flora. Unlike other strains of CoNS, however, S lugdunensis has gained notoriety for virulence that resembles Staphylococcus aureus (S aureus). S lugdunensis is now recognized as an important nosocomial pathogen and cause of prosthetic device infections, including vascular catheter infections. We present a case of persistent S lugdunensis bacteremia occurring in a patient on hemodialysis (HD) without any implanted prosthetic materials.

Case Presentation

A 60-year-old man with a history of uncontrolled type 2 diabetes mellitus (T2DM) and end-stage renal disease on home HD via arteriovenous fistula (AVF) presented to the emergency department (ED) for evaluation of subacute progressive low back pain. His symptoms began abruptly 2 weeks prior to presentation without any identifiable trigger or trauma. His pain localized to the lower thoracic spine, radiating anteriorly into his abdomen. He reported tactile fever for several days before presentation but no chills, night sweats, paresthesia, weakness, or bowel/bladder incontinence. He had no recent surgeries, implanted hardware, or invasive procedures involving the spine. HD was performed 5 times a week at home with a family member cannulating his AVF via buttonhole technique. He initially sought evaluation in a community hospital several days prior, where he underwent magnetic resonance imaging (MRI) of the thoracic spine. He was discharged from the community ED with oral opioids prior to the MRI results. He presented to West Los Angeles Veterans Affairs Medical Center (WLAVAMC) ED when MRI results came back indicating abnormalities and he reported recalcitrant pain.

On arrival at WLAVAMC, the patient was afebrile with a heart rate of 107 bpm and blood pressure of 152/97 mm Hg. The remainder of his vital signs were normal. The physical examination revealed midline tenderness on palpation of the distal thoracic and proximal lumbar spine. Muscle strength was 4 of 5 in the bilateral hip flexors, though this was limited by pain. The remainder of his neurologic examination was nonfocal. The cardiac examination was unremarkable with no murmurs auscultated. His left upper extremity AVF had an audible bruit and palpable thrill. The skin examination was notable for acanthosis nigricans but no areas of skin erythema or induration and no obvious stigmata of infective endocarditis.

The initial laboratory workup was remarkable for a white blood cell (WBC) count of 10.0 × 10³/µL with left shift, blood urea nitrogen level of 59 mg/dL, and creatinine level of 9.3 mg/dL. The patient’s erythrocyte sedimentation rate (ESR) was 45 mm/h (reference range, ≤ 20 mm/h) and C-reactive protein level was > 8.0 mg/L (reference range, ≤ 0.74 mg/L). Two months prior the hemoglobin A_1c had been recorded at 9.9%.

Given his intractable low back pain and elevated inflammatory markers, the patient underwent an MRI of the thoracic and lumbar spine with contrast while in the ED. This MRI revealed abnormal marrow edema in the T11-T12 vertebrae with abnormal fluid signal in the T11-T12 disc space. Subjacent paravertebral edema also was noted. There was no well-defined fluid collection or abnormal signal in the spinal cord. Taken together, these findings were concerning for T11-T12 discitis with osteomyelitis.

Discussion

CoNS are a major contributor to human skin flora, a common contaminant of blood cultures, and an important cause of nosocomial bloodstream infections.^1,2 These species have a predilection for forming biofilms, making CoNS a major cause of prosthetic device infections.³ S lugdunensis is a CoNS species that was first described in 1988.⁴ In addition to foreign body–related infections, S lugdunensis has been implicated in bone/joint infections, native valve endocarditis, toxic shock syndrome, and brain abscesses.^5-8 Infections due to S lugdunensis are notorious for their aggressive and fulminant courses. With its increased virulence that is atypical of other CoNS, S lugdunensis has understandably been likened more to S aureus.

Prior cases have been reported of S lugdunensis bacteremia in patients using HD. However, the suspected source of bacteremia in these cases has generally been central venous catheters.^9-12

Conclusions

S lugdunensis is an increasingly recognized cause of nosocomial bloodstream infections. Given the commonalities in virulence that S lugdunensis shares with S aureus, treatment of bacteremia caused by either species should follow similar management principles: prompt initiation of IV antistaphylococcal therapy, a thorough evaluation for the source(s) of bacteremia as well as metastatic complications, and consultation with an infectious disease specialist. This case report also highlights the importance of considering a patient’s AVF as a potential source for infection even in the absence of localized signs of infection. The buttonhole method of AVF cannulation was thought to be a major contributor to the development and persistence of our patient’s bacteremia. This risk should be discussed with patients using a shared decision-making approach when developing a dialysis treatment plan.

Compared with hemodialysis (HD), peritoneal dialysis (PD) offers comparable survival and superior patient-centered and health services outcomes.^1,2 This has prompted repeated calls over the past 2 decades for policies to increase the use of home dialysis and, more specifically, for PD in the United States.^3,4

Veterans comprise nearly 10% of the population with end-stage kidney disease (ESKD) burden; > 50,000 US veterans are currently on dialysis.^5,6 A majority of these veterans receive their chronic kidney disease (CKD) care through their affiliated US Department of Veterans Affairs (VA) medical centers (VAMCs).

Step 1: Prerequisites

A functional nephrology service is a bedrock prerequisite for establishing a new PD program. A clinician champion capable of leading the effort is equally necessary. Occasionally, the prevalent ESKD economic and health care burden prompts local VAMC leadership to consider a new PD program to improve the quality or availability of services. More commonly, though, the nephrology section and the clinician champion are the first to recognize the need. In either scenario, the champion will require support and advocacy at multiple levels of local leadership, ie, the section or department chief, facility chief of staff, VAMC director, and the Veterans Integrated Service Network (VISN) director. The foremost task for the champion is to assess local clinical and infrastructure needs.

Goal Alignment

Any new VA nephrology program needs to be evaluated for its overall congruence with the local and national VA missions to improve the accessibility, integration, quality, and innovation of care for veterans. The following considerations are likely to apply to many VA systems.

Accessibility. A VHA directive recommends that all veterans be provided with the opportunity to choose and use any form of dialysis, especially home dialysis.⁹ Transitioning a veteran seamlessly from advanced CKD to PD requires the execution of multiple sequential processes in the pre-ESKD period, beginning with early identification of advanced CKD, timely referral to nephrology, education for shared dialysis decision making, coordination of care, and PD training and therapy.¹⁰ Splitting this sequence between VA and community-based care creates obstacles, including multiple approvals through VA Community Care Services that may substantially increase wait time and effort. This onerous process may be a significant deterrent against pursuing PD and increases the odds of emergency or inpatient initiation. Furthermore, the lack of PD availability limits the knowledge and experience among staff designated to assist veterans, which may result in inappropriate advocacy for HD or delay the transition to PD. Together, these processes can increase morbidity and health care use, and significantly delay or eliminate PD. Finally, many veterans reside in rural or remote areas where the expertise and the availability of PD may be unreliable. Establishing PD services within the local VAMC can improve access to PD, reduce the lead time needed to coordinate the transition to ESKD, and assist individual veterans in making an informed choice about dialysis. The program champion will need to identify and highlight all accessibility barriers within their business plan.

Integration. Many veterans receiving dialysis care at community-based facilities continue to receive nonnephrology care in the VA. This creates a parallel health care system with concerns for duplication of efforts and processes, suboptimal quality of care, and increased risk of medical errors. Establishing VA PD services increases access and integration of nephrology with other VA care.

Excellence. Studies of many chronic diseases have shown superior patient satisfaction and equal or superior quality of care delivered by the VA compared with that of non-VA facilities.^11-14 Similarly, mortality rates for veterans receiving CKD and ESKD care in VA are lower compared with those at non-VA facilities.^15-17 While these outcomes have not been examined for PD, integration of PD with VA care may lead to an improved overall quality of care and greater loyalty to the VA.

Innovation. Due to its integrated health care infrastructure, the VA is uniquely positioned to implement patient-centered and evidence-based pre-ESKD interventions that may improve outcomes. Prior studies have shown that pre-ESKD kidney disease education (KDE) improves pre- and post-ESKD outcomes, reduces health care costs, and leads to higher selection and use of home dialysis therapies.^18-20 The VA recommends that all veterans with advanced CKD be provided access to pre-ESKD care and KDE. Unfortunately, KDE is uncommon among non-VA clinicians. A recent USRDS analysis reported that < 1% of patients with ESKD received pre-ESKD KDE.²¹ The ongoing Evaluate and Assess the effects of Comprehensive Pre-ESKD kidney disease Education on home dialysis in Veterans Trial (NCT04064086) should provide further evidence.

Step 2: Feasibility

A business plan requires the realistic projections of the costs and accounting for gains of the new clinical program. While there is limited guidance on personnel requirements when planning a PD program, we provide estimated resources needed to successfully establish and run a PD program (eAppendix 1, available online at doi:10.12788/fp.0356).

Clinical Considerations

Secondary or tertiary care VAMCs with multiple medical and surgical specialties routinely provide complex inpatient care. For these facilities, the lack of inpatient PD poses an obstacle to the provision of specialized nonnephrology care to veterans with ESKD, who are frequent users of such complex care. These considerations argue for the need for at least inpatient PD services at VAMCs that provide complex medical care for many veterans receiving PD in the community.

Deliberations for outpatient PD programs should be based on the clinical demands of ESKD care, the number of veterans likely to use PD, and growth projections. While there is no established minimum number that guarantees cost-effectiveness, most existing VA outpatient PD programs provide services for about 5 to 25 veterans. A local census can provide estimations of future PD needs. Travel considerations (ie, distance, terrain, traffic) may affect eligibility for purchased care and the decision where to receive PD. Many veterans may prefer PD from the local VAMC if it is convenient and allows them to maintain centralized VA care. Potential patients can be surveyed to gauge interest in receiving VA-based PD. Facilities providing structured pre-ESKD KDE may hold greater potential for PD growth, and it is important to highlight KDE infrastructure in the business plan.

Infrastructure

Spatial needs including clinic space and storage space for consumables, supplies, and equipment should be part of infrastructure requirements. The program champion may need to examine the available space for suitability and adequacy of the PD program early in the process. Ventilation renovations in the PD rooms should be incorporated into budget calculations. Water access for handwashing and PD effluent drainage should be confirmed, and if the program intends to establish home HD, additional considerations for the storage and water supply may be required. The VHA Handbook outlines the infrastructure requirements for a dialysis program.²² The VA has established national vendor contracts for dialysis equipment and consumables. However, a new PD program may need further guidance regarding the local agencies that provide administrative support and assist patients.

Telehealth technology has enabled many VAMCs to overcome geographical barriers for rural veterans.²³ Ongoing expansion of community-based outpatient clinics (CBOCs) to include more rural locations is improving access to specialty care, while the launch of VA Video Connect (VVC) has further improved outreach. Investigators from Minneapolis have demonstrated the feasibility of multidisciplinary home-based telehealth management of veterans with CKD.²⁴ Several existing nephrology sections across the VHA use a combination of VVC and CBOC-facilitated clinic visits to provide some pre-ESKD and ESKD care, including KDE, PD home visits and training, and comprehensive ESKD care visits. Recent changes in the clinical care pattern during the COVID-19 pandemic have further eased ESKD telehealth protocols. Integrating the projected use of telehealth in collaboration with existing resources available through the VHA NKDP can allow the local champion to improve the financial feasibility and long-term success of a new PD program.

Clinicians

Experience and expertise in managing PD vary among nephrologists. A recent survey found that only 11% of second-year nephrology trainees felt fully prepared to manage PD patients and 27% felt that they were minimally prepared.²⁵ Thus, it is important to ensure that adequately trained nephrologists are available locally before initiating a new program, and if needed, coverage across VHS or VISN can be explored. One potential method to enhance practitioner comfort in PD is the use of existing peer-to-peer education through the VA Kidney Specialty Care Access Network-Extension for Community Health care Outcomes program that links health care professionals in rural areas with specialists at a tertiary care center.²³ Nurses are a primary pillar for the success of home dialysis programs and the lack of a trained nursing workforce can be a significant limitation. Similarly, while the placement and management of complications related to PD catheters are not technically challenging, the availability of interventionists (either a surgeon or trained interventional radiologist) should be part of the business plan.

Financial Considerations

The financial considerations involving a new PD program within the VHA are complex (eAppendix 2, available online at doi:10.12788/fp.0356). ESKD is one of the most complex and costly comorbidities. It is a major determinant of the expenditure and revenue generation for facilities. The Veterans Equitable Resource Allocation system classifies ESKD on repeated dialysis as price category 10, indicating high complexity and cost. The VAMC workload and facility budget allocation is assessed annually and increases as the population of price group 10 veterans increases. VHA also provides additional Veterans Equitable Resource Allocation funds to VAMCs, which can improve the bottom line for VA-based dialysis units. Providing PD facilitates outpatient and inpatient management of comorbidities, allowing for substantial cost savings while improving the quality of nonrenal care. Outsourcing dialysis care can reduce the administrative burden, although, it deprives the VAMC of all dialysis-associated revenues while bearing the cost of all nonrenal and some renal care. The net effect is reduced facility productivity. In aggregate, establishing a local dialysis program requires greater financial resources for the capital and personnel costs; however, if captured appropriately these funds can be a major source of revenue and savings for the local VAMC.

Indirect costs are important for financial projections. Most community dialysis units operate as outpatient units, whereas all but a handful of the VA dialysis units operate within or near a VAMC. As a result, the VA units providing maintenance dialysis are regularly classified as inpatient centers while providing largely outpatient services, which negatively impacts overhead cost calculations. The predominant use of in-center HD as the default modality further sets an erroneously high baseline for the indirect cost of the VA-based PD services, especially considering that the principal savings of the home dialysis are through the reduction in the labor and capital costs. A rudimentary make-buy model for the in-center HD is available through the NKDP, and establishing a similar model for PD programs may be useful.

Cost considerations also may vary based on the model of ESKD care used locally. Of the 71 hospital-based and free-standing VA HD facilities, only 33 provide PD services, with 5 units providing only inpatient PD. The financial burden of establishing a fully operational outpatient PD program will be based on whether it is targeting a new unit or is expanding. The costs for equipment rental, disposables, and supplies vary based on the VA contract negotiations but are standardized across the nation with approved cost-of-living geographic adjustments. Caution needs to be exercised in employing a phased-hiring approach, as newer programs may require proportionally larger nursing resources due to greater needs for KDE, transitioning services, and training for PD. A target census-based hiring schedule should be negotiated with leadership before launch. If existing labor mapping does not allow for cross-coverage, part-time positions for physicians may be considered. Travel nurses, especially for PD training, can be considered to meet labor needs when long-term projections prohibit permanent full-time hires.

Finally, the balance sheet of a new program needs to account for different scenarios. In addition to nephrology costs, outsourcing veterans for PD services incurs multiple costs (eg, administrative, social work). Facilities with inpatient PD services alone are likely already bearing a component of the medications (including antibiotics) and/or surgical costs for their outsourced patients. These hidden costs are infrequently counted in projections. Facilities without inpatient PD cannot provide complex nonrenal care to ESKD patients on PD, even when the center is well equipped to provide it. These facilities also bear the cost of outsourcing even for complications related to PD. While a full estimation of these services varies, the hidden cost savings of many procedures or inpatient admissions, such as cardiovascular or musculoskeletal surgeries, can exceed those of dialysis in this complex population.

Step 3: proposal

There are no standardized formats for presenting a VHA business proposal; however, this outline provides a template. The business proposal should be designed to effectively communicate the collective data that describe the needs and requirements of a PD program to the local, regional, and national leadership. Not every rationale presented here will apply to an individual proposal and the local champion will need to tailor their rationale for their locale. A sample business plan is shown in eAppendix 3 (available online at doi:10.12788/fp.0356). VHA Handbook of dialysis requires that a PD nurse has a minimum of 12 months of nursing experience with at least 3 months of PD experience.²⁵ Nursing training, education, and support should be discussed with nursing leadership and included in the business plan. Similarly, arrangements for laboratory, pharmacy, and prosthetics services and/or logistics to facilitate procurement of the needed devices, disposables, and supplies are essential and should be highlighted in the business plan.

Approval Process

Postapproval Process

Once approved, the champion will need to work closely with various services and managers to oversee infrastructural renovations and execute the hiring plans, establish standard operating procedures (SOPs), standardize staff proficiencies and functional statements, and finalize quality assessment parameters. Home dialysis standards have been addressed by NKDP and The Joint Commission. While PD requires home visits to assess the appropriateness of the environment, the PD program is accredited under hospital-based therapy. Standards and performance metrics should be incorporated into all the VA PD programs for standardization and assessment. Based on guidance from the VHA Handbook, quality metrics, such as dialysis adequacy, and rates of infection should be monitored and reviewed. The dialysis director may need to consider more frequent program evaluations in the first year to ensure appropriate troubleshooting. The VA infrastructure has developed the resources for a central repository for the PD SOPs and quality metrics, which can be obtained and adapted for the local program. Similarly, veteran satisfaction can be assessed through existing resources. Finally, the dialysis director can join the National VHA Dialysis Director listserv for regular updates on the existing and new VHA policies and NKDP updates.

Conclusions

Establishing a new PD program within a local federal infrastructure can appear daunting, both in terms of planning as well as approvals. However, the provision of home-based dialysis therapies may be beneficial to those in rural settings with limited access to in-center dialysis modalities as well as to those who seek autonomy and lifestyle independence in their medical care. Collaborations with the VHA NKDP or PD workgroup can help overcome many of the procedural hurdles, provide guidance about infrastructure and resource allocation and utilization, and provide easy access to established SOPs and quality parameters.

Acknowledgments

We acknowledge the late Dr. Catherine Do for her significant contribution to this manuscript. We also extend our sincere thanks to Dr. Holly Mattix-Kramer (Edward Hines Jr. Veterans Affairs Hospital and Loyola University Medical Center) for her prompt and valuable feedback on this manuscript.

Compared with hemodialysis (HD), peritoneal dialysis (PD) offers comparable survival and superior patient-centered and health services outcomes.^1,2 This has prompted repeated calls over the past 2 decades for policies to increase the use of home dialysis and, more specifically, for PD in the United States.^3,4

Veterans comprise nearly 10% of the population with end-stage kidney disease (ESKD) burden; > 50,000 US veterans are currently on dialysis.^5,6 A majority of these veterans receive their chronic kidney disease (CKD) care through their affiliated US Department of Veterans Affairs (VA) medical centers (VAMCs).

Step 1: Prerequisites

A functional nephrology service is a bedrock prerequisite for establishing a new PD program. A clinician champion capable of leading the effort is equally necessary. Occasionally, the prevalent ESKD economic and health care burden prompts local VAMC leadership to consider a new PD program to improve the quality or availability of services. More commonly, though, the nephrology section and the clinician champion are the first to recognize the need. In either scenario, the champion will require support and advocacy at multiple levels of local leadership, ie, the section or department chief, facility chief of staff, VAMC director, and the Veterans Integrated Service Network (VISN) director. The foremost task for the champion is to assess local clinical and infrastructure needs.

Goal Alignment

Any new VA nephrology program needs to be evaluated for its overall congruence with the local and national VA missions to improve the accessibility, integration, quality, and innovation of care for veterans. The following considerations are likely to apply to many VA systems.

Accessibility. A VHA directive recommends that all veterans be provided with the opportunity to choose and use any form of dialysis, especially home dialysis.⁹ Transitioning a veteran seamlessly from advanced CKD to PD requires the execution of multiple sequential processes in the pre-ESKD period, beginning with early identification of advanced CKD, timely referral to nephrology, education for shared dialysis decision making, coordination of care, and PD training and therapy.¹⁰ Splitting this sequence between VA and community-based care creates obstacles, including multiple approvals through VA Community Care Services that may substantially increase wait time and effort. This onerous process may be a significant deterrent against pursuing PD and increases the odds of emergency or inpatient initiation. Furthermore, the lack of PD availability limits the knowledge and experience among staff designated to assist veterans, which may result in inappropriate advocacy for HD or delay the transition to PD. Together, these processes can increase morbidity and health care use, and significantly delay or eliminate PD. Finally, many veterans reside in rural or remote areas where the expertise and the availability of PD may be unreliable. Establishing PD services within the local VAMC can improve access to PD, reduce the lead time needed to coordinate the transition to ESKD, and assist individual veterans in making an informed choice about dialysis. The program champion will need to identify and highlight all accessibility barriers within their business plan.

Integration. Many veterans receiving dialysis care at community-based facilities continue to receive nonnephrology care in the VA. This creates a parallel health care system with concerns for duplication of efforts and processes, suboptimal quality of care, and increased risk of medical errors. Establishing VA PD services increases access and integration of nephrology with other VA care.

Excellence. Studies of many chronic diseases have shown superior patient satisfaction and equal or superior quality of care delivered by the VA compared with that of non-VA facilities.^11-14 Similarly, mortality rates for veterans receiving CKD and ESKD care in VA are lower compared with those at non-VA facilities.^15-17 While these outcomes have not been examined for PD, integration of PD with VA care may lead to an improved overall quality of care and greater loyalty to the VA.

Innovation. Due to its integrated health care infrastructure, the VA is uniquely positioned to implement patient-centered and evidence-based pre-ESKD interventions that may improve outcomes. Prior studies have shown that pre-ESKD kidney disease education (KDE) improves pre- and post-ESKD outcomes, reduces health care costs, and leads to higher selection and use of home dialysis therapies.^18-20 The VA recommends that all veterans with advanced CKD be provided access to pre-ESKD care and KDE. Unfortunately, KDE is uncommon among non-VA clinicians. A recent USRDS analysis reported that < 1% of patients with ESKD received pre-ESKD KDE.²¹ The ongoing Evaluate and Assess the effects of Comprehensive Pre-ESKD kidney disease Education on home dialysis in Veterans Trial (NCT04064086) should provide further evidence.

Step 2: Feasibility

A business plan requires the realistic projections of the costs and accounting for gains of the new clinical program. While there is limited guidance on personnel requirements when planning a PD program, we provide estimated resources needed to successfully establish and run a PD program (eAppendix 1, available online at doi:10.12788/fp.0356).

Clinical Considerations

Secondary or tertiary care VAMCs with multiple medical and surgical specialties routinely provide complex inpatient care. For these facilities, the lack of inpatient PD poses an obstacle to the provision of specialized nonnephrology care to veterans with ESKD, who are frequent users of such complex care. These considerations argue for the need for at least inpatient PD services at VAMCs that provide complex medical care for many veterans receiving PD in the community.

Deliberations for outpatient PD programs should be based on the clinical demands of ESKD care, the number of veterans likely to use PD, and growth projections. While there is no established minimum number that guarantees cost-effectiveness, most existing VA outpatient PD programs provide services for about 5 to 25 veterans. A local census can provide estimations of future PD needs. Travel considerations (ie, distance, terrain, traffic) may affect eligibility for purchased care and the decision where to receive PD. Many veterans may prefer PD from the local VAMC if it is convenient and allows them to maintain centralized VA care. Potential patients can be surveyed to gauge interest in receiving VA-based PD. Facilities providing structured pre-ESKD KDE may hold greater potential for PD growth, and it is important to highlight KDE infrastructure in the business plan.

Infrastructure

Spatial needs including clinic space and storage space for consumables, supplies, and equipment should be part of infrastructure requirements. The program champion may need to examine the available space for suitability and adequacy of the PD program early in the process. Ventilation renovations in the PD rooms should be incorporated into budget calculations. Water access for handwashing and PD effluent drainage should be confirmed, and if the program intends to establish home HD, additional considerations for the storage and water supply may be required. The VHA Handbook outlines the infrastructure requirements for a dialysis program.²² The VA has established national vendor contracts for dialysis equipment and consumables. However, a new PD program may need further guidance regarding the local agencies that provide administrative support and assist patients.

Telehealth technology has enabled many VAMCs to overcome geographical barriers for rural veterans.²³ Ongoing expansion of community-based outpatient clinics (CBOCs) to include more rural locations is improving access to specialty care, while the launch of VA Video Connect (VVC) has further improved outreach. Investigators from Minneapolis have demonstrated the feasibility of multidisciplinary home-based telehealth management of veterans with CKD.²⁴ Several existing nephrology sections across the VHA use a combination of VVC and CBOC-facilitated clinic visits to provide some pre-ESKD and ESKD care, including KDE, PD home visits and training, and comprehensive ESKD care visits. Recent changes in the clinical care pattern during the COVID-19 pandemic have further eased ESKD telehealth protocols. Integrating the projected use of telehealth in collaboration with existing resources available through the VHA NKDP can allow the local champion to improve the financial feasibility and long-term success of a new PD program.

Clinicians

Experience and expertise in managing PD vary among nephrologists. A recent survey found that only 11% of second-year nephrology trainees felt fully prepared to manage PD patients and 27% felt that they were minimally prepared.²⁵ Thus, it is important to ensure that adequately trained nephrologists are available locally before initiating a new program, and if needed, coverage across VHS or VISN can be explored. One potential method to enhance practitioner comfort in PD is the use of existing peer-to-peer education through the VA Kidney Specialty Care Access Network-Extension for Community Health care Outcomes program that links health care professionals in rural areas with specialists at a tertiary care center.²³ Nurses are a primary pillar for the success of home dialysis programs and the lack of a trained nursing workforce can be a significant limitation. Similarly, while the placement and management of complications related to PD catheters are not technically challenging, the availability of interventionists (either a surgeon or trained interventional radiologist) should be part of the business plan.

Financial Considerations

The financial considerations involving a new PD program within the VHA are complex (eAppendix 2, available online at doi:10.12788/fp.0356). ESKD is one of the most complex and costly comorbidities. It is a major determinant of the expenditure and revenue generation for facilities. The Veterans Equitable Resource Allocation system classifies ESKD on repeated dialysis as price category 10, indicating high complexity and cost. The VAMC workload and facility budget allocation is assessed annually and increases as the population of price group 10 veterans increases. VHA also provides additional Veterans Equitable Resource Allocation funds to VAMCs, which can improve the bottom line for VA-based dialysis units. Providing PD facilitates outpatient and inpatient management of comorbidities, allowing for substantial cost savings while improving the quality of nonrenal care. Outsourcing dialysis care can reduce the administrative burden, although, it deprives the VAMC of all dialysis-associated revenues while bearing the cost of all nonrenal and some renal care. The net effect is reduced facility productivity. In aggregate, establishing a local dialysis program requires greater financial resources for the capital and personnel costs; however, if captured appropriately these funds can be a major source of revenue and savings for the local VAMC.

Indirect costs are important for financial projections. Most community dialysis units operate as outpatient units, whereas all but a handful of the VA dialysis units operate within or near a VAMC. As a result, the VA units providing maintenance dialysis are regularly classified as inpatient centers while providing largely outpatient services, which negatively impacts overhead cost calculations. The predominant use of in-center HD as the default modality further sets an erroneously high baseline for the indirect cost of the VA-based PD services, especially considering that the principal savings of the home dialysis are through the reduction in the labor and capital costs. A rudimentary make-buy model for the in-center HD is available through the NKDP, and establishing a similar model for PD programs may be useful.

Cost considerations also may vary based on the model of ESKD care used locally. Of the 71 hospital-based and free-standing VA HD facilities, only 33 provide PD services, with 5 units providing only inpatient PD. The financial burden of establishing a fully operational outpatient PD program will be based on whether it is targeting a new unit or is expanding. The costs for equipment rental, disposables, and supplies vary based on the VA contract negotiations but are standardized across the nation with approved cost-of-living geographic adjustments. Caution needs to be exercised in employing a phased-hiring approach, as newer programs may require proportionally larger nursing resources due to greater needs for KDE, transitioning services, and training for PD. A target census-based hiring schedule should be negotiated with leadership before launch. If existing labor mapping does not allow for cross-coverage, part-time positions for physicians may be considered. Travel nurses, especially for PD training, can be considered to meet labor needs when long-term projections prohibit permanent full-time hires.

Finally, the balance sheet of a new program needs to account for different scenarios. In addition to nephrology costs, outsourcing veterans for PD services incurs multiple costs (eg, administrative, social work). Facilities with inpatient PD services alone are likely already bearing a component of the medications (including antibiotics) and/or surgical costs for their outsourced patients. These hidden costs are infrequently counted in projections. Facilities without inpatient PD cannot provide complex nonrenal care to ESKD patients on PD, even when the center is well equipped to provide it. These facilities also bear the cost of outsourcing even for complications related to PD. While a full estimation of these services varies, the hidden cost savings of many procedures or inpatient admissions, such as cardiovascular or musculoskeletal surgeries, can exceed those of dialysis in this complex population.

Step 3: proposal

There are no standardized formats for presenting a VHA business proposal; however, this outline provides a template. The business proposal should be designed to effectively communicate the collective data that describe the needs and requirements of a PD program to the local, regional, and national leadership. Not every rationale presented here will apply to an individual proposal and the local champion will need to tailor their rationale for their locale. A sample business plan is shown in eAppendix 3 (available online at doi:10.12788/fp.0356). VHA Handbook of dialysis requires that a PD nurse has a minimum of 12 months of nursing experience with at least 3 months of PD experience.²⁵ Nursing training, education, and support should be discussed with nursing leadership and included in the business plan. Similarly, arrangements for laboratory, pharmacy, and prosthetics services and/or logistics to facilitate procurement of the needed devices, disposables, and supplies are essential and should be highlighted in the business plan.

Approval Process

Postapproval Process

Once approved, the champion will need to work closely with various services and managers to oversee infrastructural renovations and execute the hiring plans, establish standard operating procedures (SOPs), standardize staff proficiencies and functional statements, and finalize quality assessment parameters. Home dialysis standards have been addressed by NKDP and The Joint Commission. While PD requires home visits to assess the appropriateness of the environment, the PD program is accredited under hospital-based therapy. Standards and performance metrics should be incorporated into all the VA PD programs for standardization and assessment. Based on guidance from the VHA Handbook, quality metrics, such as dialysis adequacy, and rates of infection should be monitored and reviewed. The dialysis director may need to consider more frequent program evaluations in the first year to ensure appropriate troubleshooting. The VA infrastructure has developed the resources for a central repository for the PD SOPs and quality metrics, which can be obtained and adapted for the local program. Similarly, veteran satisfaction can be assessed through existing resources. Finally, the dialysis director can join the National VHA Dialysis Director listserv for regular updates on the existing and new VHA policies and NKDP updates.

Conclusions

Establishing a new PD program within a local federal infrastructure can appear daunting, both in terms of planning as well as approvals. However, the provision of home-based dialysis therapies may be beneficial to those in rural settings with limited access to in-center dialysis modalities as well as to those who seek autonomy and lifestyle independence in their medical care. Collaborations with the VHA NKDP or PD workgroup can help overcome many of the procedural hurdles, provide guidance about infrastructure and resource allocation and utilization, and provide easy access to established SOPs and quality parameters.

Acknowledgments

We acknowledge the late Dr. Catherine Do for her significant contribution to this manuscript. We also extend our sincere thanks to Dr. Holly Mattix-Kramer (Edward Hines Jr. Veterans Affairs Hospital and Loyola University Medical Center) for her prompt and valuable feedback on this manuscript.

Compared with hemodialysis (HD), peritoneal dialysis (PD) offers comparable survival and superior patient-centered and health services outcomes.^1,2 This has prompted repeated calls over the past 2 decades for policies to increase the use of home dialysis and, more specifically, for PD in the United States.^3,4

Veterans comprise nearly 10% of the population with end-stage kidney disease (ESKD) burden; > 50,000 US veterans are currently on dialysis.^5,6 A majority of these veterans receive their chronic kidney disease (CKD) care through their affiliated US Department of Veterans Affairs (VA) medical centers (VAMCs).

Step 1: Prerequisites

A functional nephrology service is a bedrock prerequisite for establishing a new PD program. A clinician champion capable of leading the effort is equally necessary. Occasionally, the prevalent ESKD economic and health care burden prompts local VAMC leadership to consider a new PD program to improve the quality or availability of services. More commonly, though, the nephrology section and the clinician champion are the first to recognize the need. In either scenario, the champion will require support and advocacy at multiple levels of local leadership, ie, the section or department chief, facility chief of staff, VAMC director, and the Veterans Integrated Service Network (VISN) director. The foremost task for the champion is to assess local clinical and infrastructure needs.

Goal Alignment

Any new VA nephrology program needs to be evaluated for its overall congruence with the local and national VA missions to improve the accessibility, integration, quality, and innovation of care for veterans. The following considerations are likely to apply to many VA systems.

Accessibility. A VHA directive recommends that all veterans be provided with the opportunity to choose and use any form of dialysis, especially home dialysis.⁹ Transitioning a veteran seamlessly from advanced CKD to PD requires the execution of multiple sequential processes in the pre-ESKD period, beginning with early identification of advanced CKD, timely referral to nephrology, education for shared dialysis decision making, coordination of care, and PD training and therapy.¹⁰ Splitting this sequence between VA and community-based care creates obstacles, including multiple approvals through VA Community Care Services that may substantially increase wait time and effort. This onerous process may be a significant deterrent against pursuing PD and increases the odds of emergency or inpatient initiation. Furthermore, the lack of PD availability limits the knowledge and experience among staff designated to assist veterans, which may result in inappropriate advocacy for HD or delay the transition to PD. Together, these processes can increase morbidity and health care use, and significantly delay or eliminate PD. Finally, many veterans reside in rural or remote areas where the expertise and the availability of PD may be unreliable. Establishing PD services within the local VAMC can improve access to PD, reduce the lead time needed to coordinate the transition to ESKD, and assist individual veterans in making an informed choice about dialysis. The program champion will need to identify and highlight all accessibility barriers within their business plan.

Integration. Many veterans receiving dialysis care at community-based facilities continue to receive nonnephrology care in the VA. This creates a parallel health care system with concerns for duplication of efforts and processes, suboptimal quality of care, and increased risk of medical errors. Establishing VA PD services increases access and integration of nephrology with other VA care.

Excellence. Studies of many chronic diseases have shown superior patient satisfaction and equal or superior quality of care delivered by the VA compared with that of non-VA facilities.^11-14 Similarly, mortality rates for veterans receiving CKD and ESKD care in VA are lower compared with those at non-VA facilities.^15-17 While these outcomes have not been examined for PD, integration of PD with VA care may lead to an improved overall quality of care and greater loyalty to the VA.

Innovation. Due to its integrated health care infrastructure, the VA is uniquely positioned to implement patient-centered and evidence-based pre-ESKD interventions that may improve outcomes. Prior studies have shown that pre-ESKD kidney disease education (KDE) improves pre- and post-ESKD outcomes, reduces health care costs, and leads to higher selection and use of home dialysis therapies.^18-20 The VA recommends that all veterans with advanced CKD be provided access to pre-ESKD care and KDE. Unfortunately, KDE is uncommon among non-VA clinicians. A recent USRDS analysis reported that < 1% of patients with ESKD received pre-ESKD KDE.²¹ The ongoing Evaluate and Assess the effects of Comprehensive Pre-ESKD kidney disease Education on home dialysis in Veterans Trial (NCT04064086) should provide further evidence.

Step 2: Feasibility

A business plan requires the realistic projections of the costs and accounting for gains of the new clinical program. While there is limited guidance on personnel requirements when planning a PD program, we provide estimated resources needed to successfully establish and run a PD program (eAppendix 1, available online at doi:10.12788/fp.0356).

Clinical Considerations

Secondary or tertiary care VAMCs with multiple medical and surgical specialties routinely provide complex inpatient care. For these facilities, the lack of inpatient PD poses an obstacle to the provision of specialized nonnephrology care to veterans with ESKD, who are frequent users of such complex care. These considerations argue for the need for at least inpatient PD services at VAMCs that provide complex medical care for many veterans receiving PD in the community.

Deliberations for outpatient PD programs should be based on the clinical demands of ESKD care, the number of veterans likely to use PD, and growth projections. While there is no established minimum number that guarantees cost-effectiveness, most existing VA outpatient PD programs provide services for about 5 to 25 veterans. A local census can provide estimations of future PD needs. Travel considerations (ie, distance, terrain, traffic) may affect eligibility for purchased care and the decision where to receive PD. Many veterans may prefer PD from the local VAMC if it is convenient and allows them to maintain centralized VA care. Potential patients can be surveyed to gauge interest in receiving VA-based PD. Facilities providing structured pre-ESKD KDE may hold greater potential for PD growth, and it is important to highlight KDE infrastructure in the business plan.

Infrastructure

Spatial needs including clinic space and storage space for consumables, supplies, and equipment should be part of infrastructure requirements. The program champion may need to examine the available space for suitability and adequacy of the PD program early in the process. Ventilation renovations in the PD rooms should be incorporated into budget calculations. Water access for handwashing and PD effluent drainage should be confirmed, and if the program intends to establish home HD, additional considerations for the storage and water supply may be required. The VHA Handbook outlines the infrastructure requirements for a dialysis program.²² The VA has established national vendor contracts for dialysis equipment and consumables. However, a new PD program may need further guidance regarding the local agencies that provide administrative support and assist patients.

Telehealth technology has enabled many VAMCs to overcome geographical barriers for rural veterans.²³ Ongoing expansion of community-based outpatient clinics (CBOCs) to include more rural locations is improving access to specialty care, while the launch of VA Video Connect (VVC) has further improved outreach. Investigators from Minneapolis have demonstrated the feasibility of multidisciplinary home-based telehealth management of veterans with CKD.²⁴ Several existing nephrology sections across the VHA use a combination of VVC and CBOC-facilitated clinic visits to provide some pre-ESKD and ESKD care, including KDE, PD home visits and training, and comprehensive ESKD care visits. Recent changes in the clinical care pattern during the COVID-19 pandemic have further eased ESKD telehealth protocols. Integrating the projected use of telehealth in collaboration with existing resources available through the VHA NKDP can allow the local champion to improve the financial feasibility and long-term success of a new PD program.

Clinicians

Experience and expertise in managing PD vary among nephrologists. A recent survey found that only 11% of second-year nephrology trainees felt fully prepared to manage PD patients and 27% felt that they were minimally prepared.²⁵ Thus, it is important to ensure that adequately trained nephrologists are available locally before initiating a new program, and if needed, coverage across VHS or VISN can be explored. One potential method to enhance practitioner comfort in PD is the use of existing peer-to-peer education through the VA Kidney Specialty Care Access Network-Extension for Community Health care Outcomes program that links health care professionals in rural areas with specialists at a tertiary care center.²³ Nurses are a primary pillar for the success of home dialysis programs and the lack of a trained nursing workforce can be a significant limitation. Similarly, while the placement and management of complications related to PD catheters are not technically challenging, the availability of interventionists (either a surgeon or trained interventional radiologist) should be part of the business plan.

Financial Considerations

The financial considerations involving a new PD program within the VHA are complex (eAppendix 2, available online at doi:10.12788/fp.0356). ESKD is one of the most complex and costly comorbidities. It is a major determinant of the expenditure and revenue generation for facilities. The Veterans Equitable Resource Allocation system classifies ESKD on repeated dialysis as price category 10, indicating high complexity and cost. The VAMC workload and facility budget allocation is assessed annually and increases as the population of price group 10 veterans increases. VHA also provides additional Veterans Equitable Resource Allocation funds to VAMCs, which can improve the bottom line for VA-based dialysis units. Providing PD facilitates outpatient and inpatient management of comorbidities, allowing for substantial cost savings while improving the quality of nonrenal care. Outsourcing dialysis care can reduce the administrative burden, although, it deprives the VAMC of all dialysis-associated revenues while bearing the cost of all nonrenal and some renal care. The net effect is reduced facility productivity. In aggregate, establishing a local dialysis program requires greater financial resources for the capital and personnel costs; however, if captured appropriately these funds can be a major source of revenue and savings for the local VAMC.

Indirect costs are important for financial projections. Most community dialysis units operate as outpatient units, whereas all but a handful of the VA dialysis units operate within or near a VAMC. As a result, the VA units providing maintenance dialysis are regularly classified as inpatient centers while providing largely outpatient services, which negatively impacts overhead cost calculations. The predominant use of in-center HD as the default modality further sets an erroneously high baseline for the indirect cost of the VA-based PD services, especially considering that the principal savings of the home dialysis are through the reduction in the labor and capital costs. A rudimentary make-buy model for the in-center HD is available through the NKDP, and establishing a similar model for PD programs may be useful.

Cost considerations also may vary based on the model of ESKD care used locally. Of the 71 hospital-based and free-standing VA HD facilities, only 33 provide PD services, with 5 units providing only inpatient PD. The financial burden of establishing a fully operational outpatient PD program will be based on whether it is targeting a new unit or is expanding. The costs for equipment rental, disposables, and supplies vary based on the VA contract negotiations but are standardized across the nation with approved cost-of-living geographic adjustments. Caution needs to be exercised in employing a phased-hiring approach, as newer programs may require proportionally larger nursing resources due to greater needs for KDE, transitioning services, and training for PD. A target census-based hiring schedule should be negotiated with leadership before launch. If existing labor mapping does not allow for cross-coverage, part-time positions for physicians may be considered. Travel nurses, especially for PD training, can be considered to meet labor needs when long-term projections prohibit permanent full-time hires.

Finally, the balance sheet of a new program needs to account for different scenarios. In addition to nephrology costs, outsourcing veterans for PD services incurs multiple costs (eg, administrative, social work). Facilities with inpatient PD services alone are likely already bearing a component of the medications (including antibiotics) and/or surgical costs for their outsourced patients. These hidden costs are infrequently counted in projections. Facilities without inpatient PD cannot provide complex nonrenal care to ESKD patients on PD, even when the center is well equipped to provide it. These facilities also bear the cost of outsourcing even for complications related to PD. While a full estimation of these services varies, the hidden cost savings of many procedures or inpatient admissions, such as cardiovascular or musculoskeletal surgeries, can exceed those of dialysis in this complex population.

Step 3: proposal

There are no standardized formats for presenting a VHA business proposal; however, this outline provides a template. The business proposal should be designed to effectively communicate the collective data that describe the needs and requirements of a PD program to the local, regional, and national leadership. Not every rationale presented here will apply to an individual proposal and the local champion will need to tailor their rationale for their locale. A sample business plan is shown in eAppendix 3 (available online at doi:10.12788/fp.0356). VHA Handbook of dialysis requires that a PD nurse has a minimum of 12 months of nursing experience with at least 3 months of PD experience.²⁵ Nursing training, education, and support should be discussed with nursing leadership and included in the business plan. Similarly, arrangements for laboratory, pharmacy, and prosthetics services and/or logistics to facilitate procurement of the needed devices, disposables, and supplies are essential and should be highlighted in the business plan.

Approval Process

Postapproval Process

Once approved, the champion will need to work closely with various services and managers to oversee infrastructural renovations and execute the hiring plans, establish standard operating procedures (SOPs), standardize staff proficiencies and functional statements, and finalize quality assessment parameters. Home dialysis standards have been addressed by NKDP and The Joint Commission. While PD requires home visits to assess the appropriateness of the environment, the PD program is accredited under hospital-based therapy. Standards and performance metrics should be incorporated into all the VA PD programs for standardization and assessment. Based on guidance from the VHA Handbook, quality metrics, such as dialysis adequacy, and rates of infection should be monitored and reviewed. The dialysis director may need to consider more frequent program evaluations in the first year to ensure appropriate troubleshooting. The VA infrastructure has developed the resources for a central repository for the PD SOPs and quality metrics, which can be obtained and adapted for the local program. Similarly, veteran satisfaction can be assessed through existing resources. Finally, the dialysis director can join the National VHA Dialysis Director listserv for regular updates on the existing and new VHA policies and NKDP updates.

Conclusions

Establishing a new PD program within a local federal infrastructure can appear daunting, both in terms of planning as well as approvals. However, the provision of home-based dialysis therapies may be beneficial to those in rural settings with limited access to in-center dialysis modalities as well as to those who seek autonomy and lifestyle independence in their medical care. Collaborations with the VHA NKDP or PD workgroup can help overcome many of the procedural hurdles, provide guidance about infrastructure and resource allocation and utilization, and provide easy access to established SOPs and quality parameters.

Acknowledgments

We acknowledge the late Dr. Catherine Do for her significant contribution to this manuscript. We also extend our sincere thanks to Dr. Holly Mattix-Kramer (Edward Hines Jr. Veterans Affairs Hospital and Loyola University Medical Center) for her prompt and valuable feedback on this manuscript.

THE COMPARISON

A Melasma on the face of a Hispanic woman, with hyperpigmentation on the cheeks, bridge of the nose, and upper lip.

B Melasma on the face of a Malaysian woman, with hyperpigmentation on the upper cheeks and bridge of the nose.

C Melasma on the face of an African woman, with hyperpigmentation on the upper cheeks and lateral to the eyes.

Melasma (also known as chloasma) is a pigmentary disorder that causes chronic symmetric hyperpigmentation on the face. In patients with darker skin tones, centrofacial areas are affected.¹ Increased deposition of melanin distributed in the dermis leads to dermal melanosis. Newer research suggests that mast cell and keratinocyte interactions, altered gene regulation, neovascularization, and disruptions in the basement membrane cause melasma.² Patients present with epidermal or dermal melasma or a combination of both (mixed melasma).³ Wood lamp examination is helpful to distinguish between epidermal and dermal melasma. Dermal and mixed melasma can be difficult to treat and require multimodal treatments.

Epidemiology

Melasma commonly affects women ages 20 to 40 years,⁴ with a female to male ratio of 9:1.⁵ Potential triggers of melasma include hormones (eg, pregnancy, oral contraceptives, hormone replacement therapy) and exposure to UV light.^2,5 Melasma occurs in patients of all racial and ethnic backgrounds; however, the prevalence is higher in patients with darker skin tones.²

Key clinical features in people with darker skin tones

Melasma commonly manifests as symmetrically distributed, reticulated (lacy), dark brown to grayish brown patches on the cheeks, nose, forehead, upper lip, and chin in patients with darker skin tones.⁵ The pigment can be tan brown in patients with lighter skin tones. Given that postinflammatory hyperpigmentation and other pigmentary disorders can cause a similar appearance, a biopsy sometimes is needed to confirm the diagnosis, but melasma is diagnosed via physical examination in most patients. Melasma can be misdiagnosed as postinflammatory hyperpigmentation, solar lentigines, exogenous ochronosis, and Hori nevus.⁵

Worth noting

Prevention

• Daily sunscreen use is critical to prevent worsening of melasma. Sunscreen may not appear cosmetically elegant on darker skin tones, which creates a barrier to its use.⁶ Protection from both sunlight and visible light is necessary. Visible light, including light from light bulbs and device-emitted blue light, can worsen melasma. Iron oxides in tinted sunscreen offer protection from visible light.
• Physicians can recommend sunscreens that are more transparent or tinted for a better cosmetic match.
• Severe flares of melasma can occur with sun exposure despite good control with medications and laser modalities.

Treatment

• First-line therapies include topical hydroquinone 2% to 4%, tretinoin, azelaic acid, kojic acid, or ascorbic acid (vitamin C). A popular topical compound is a steroid, tretinoin, and hydroquinone.^1,5 Over-the-counter hydroquinone has been removed from the market due to safety concerns; however, it is still first line in the treatment of melasma. If hydroquinone is prescribed, treatment intervals of 6 to 8 weeks followed by a hydroquinone-free period is advised to reduce the risk for exogenous ochronosis (a paradoxical darkening of the skin).
• Chemical peels are second-line treatments that are effective for melasma. Improvement in epidermal melasma has been shown with chemical peels containing Jessner solution, salicylic acid, or a-hydroxy acid. Patients with dermal and mixed melasma have seen improvement with trichloroacetic acid 25% to 35% with or without Jessner solution.¹
• Cysteamine is a topical treatment created from the degradation of coenzyme A. It disrupts the synthesis of melanin to create a more even skin tone. It may be recommended in combination with sunscreen as a first-line or secondline topical therapy.
• Oral tranexamic acid is a third-line treatment that is an analogue for lysine. It decreases prostaglandin production, which leads to a lower number of tyrosine precursors available for the creation of melanin. Tranexamic acid has been shown to lighten the appearance of melasma.⁷ The most common and dangerous adverse effect of tranexamic acid is blood clots, and this treatment should be avoided in those on combination (estrogen and progestin) contraceptives or those with a personal or family history of clotting disorders.⁸
• Fourth-line treatments such as lasers (performed by dermatologists) can destroy the deposition of pigment while avoiding destruction of epidermal keratinocytes.^1,9,10 They also are commonly employed in refractive melasma. The most common lasers are nonablative fractionated lasers and low-fluence Q-switched lasers. The Q-switched Nd:YAG and picosecond lasers are safe for treating melasma in darker skin tones. Ablative fractionated lasers such as CO₂ lasers and erbium:YAG lasers also have been used in the treatment of melasma; however, there is still an extremely high risk for postinflammatory dyspigmentation 1 to 2 months after the procedure.¹⁰
• Although there is still a risk for rebound hyperpigmentation after laser treatment, use of topical hydroquinone pretreatment may help decrease postoperative hyperpigmentation.^1,5 Patients who are treated with the incorrect laser or overtreated may develop postinflammatory hyperpigmentation, rebound hyperpigmentation, or hypopigmentation.

Health disparity highlight

Melasma, most common in patients with skin of color, is a common chronic pigmentation disorder that is cosmetically and psychologically burdensome,¹¹ leading to decreased quality of life, emotional functioning, and self-esteem.¹² Clinicians should counsel patients and work closely on long-term management. The treatment options for melasma are considered cosmetic and may be cost prohibitive for many to cover out of pocket. Topical treatments have been found to be the most cost-effective.¹³ Some compounding pharmacies and drug discount programs provide more affordable treatment pricing; however, some patients are still unable to afford these options.

THE COMPARISON

A Melasma on the face of a Hispanic woman, with hyperpigmentation on the cheeks, bridge of the nose, and upper lip.

B Melasma on the face of a Malaysian woman, with hyperpigmentation on the upper cheeks and bridge of the nose.

C Melasma on the face of an African woman, with hyperpigmentation on the upper cheeks and lateral to the eyes.

Melasma (also known as chloasma) is a pigmentary disorder that causes chronic symmetric hyperpigmentation on the face. In patients with darker skin tones, centrofacial areas are affected.¹ Increased deposition of melanin distributed in the dermis leads to dermal melanosis. Newer research suggests that mast cell and keratinocyte interactions, altered gene regulation, neovascularization, and disruptions in the basement membrane cause melasma.² Patients present with epidermal or dermal melasma or a combination of both (mixed melasma).³ Wood lamp examination is helpful to distinguish between epidermal and dermal melasma. Dermal and mixed melasma can be difficult to treat and require multimodal treatments.

Epidemiology

Melasma commonly affects women ages 20 to 40 years,⁴ with a female to male ratio of 9:1.⁵ Potential triggers of melasma include hormones (eg, pregnancy, oral contraceptives, hormone replacement therapy) and exposure to UV light.^2,5 Melasma occurs in patients of all racial and ethnic backgrounds; however, the prevalence is higher in patients with darker skin tones.²

Key clinical features in people with darker skin tones

Melasma commonly manifests as symmetrically distributed, reticulated (lacy), dark brown to grayish brown patches on the cheeks, nose, forehead, upper lip, and chin in patients with darker skin tones.⁵ The pigment can be tan brown in patients with lighter skin tones. Given that postinflammatory hyperpigmentation and other pigmentary disorders can cause a similar appearance, a biopsy sometimes is needed to confirm the diagnosis, but melasma is diagnosed via physical examination in most patients. Melasma can be misdiagnosed as postinflammatory hyperpigmentation, solar lentigines, exogenous ochronosis, and Hori nevus.⁵

Worth noting

Prevention

• Daily sunscreen use is critical to prevent worsening of melasma. Sunscreen may not appear cosmetically elegant on darker skin tones, which creates a barrier to its use.⁶ Protection from both sunlight and visible light is necessary. Visible light, including light from light bulbs and device-emitted blue light, can worsen melasma. Iron oxides in tinted sunscreen offer protection from visible light.
• Physicians can recommend sunscreens that are more transparent or tinted for a better cosmetic match.
• Severe flares of melasma can occur with sun exposure despite good control with medications and laser modalities.

Treatment

• First-line therapies include topical hydroquinone 2% to 4%, tretinoin, azelaic acid, kojic acid, or ascorbic acid (vitamin C). A popular topical compound is a steroid, tretinoin, and hydroquinone.^1,5 Over-the-counter hydroquinone has been removed from the market due to safety concerns; however, it is still first line in the treatment of melasma. If hydroquinone is prescribed, treatment intervals of 6 to 8 weeks followed by a hydroquinone-free period is advised to reduce the risk for exogenous ochronosis (a paradoxical darkening of the skin).
• Chemical peels are second-line treatments that are effective for melasma. Improvement in epidermal melasma has been shown with chemical peels containing Jessner solution, salicylic acid, or a-hydroxy acid. Patients with dermal and mixed melasma have seen improvement with trichloroacetic acid 25% to 35% with or without Jessner solution.¹
• Cysteamine is a topical treatment created from the degradation of coenzyme A. It disrupts the synthesis of melanin to create a more even skin tone. It may be recommended in combination with sunscreen as a first-line or secondline topical therapy.
• Oral tranexamic acid is a third-line treatment that is an analogue for lysine. It decreases prostaglandin production, which leads to a lower number of tyrosine precursors available for the creation of melanin. Tranexamic acid has been shown to lighten the appearance of melasma.⁷ The most common and dangerous adverse effect of tranexamic acid is blood clots, and this treatment should be avoided in those on combination (estrogen and progestin) contraceptives or those with a personal or family history of clotting disorders.⁸
• Fourth-line treatments such as lasers (performed by dermatologists) can destroy the deposition of pigment while avoiding destruction of epidermal keratinocytes.^1,9,10 They also are commonly employed in refractive melasma. The most common lasers are nonablative fractionated lasers and low-fluence Q-switched lasers. The Q-switched Nd:YAG and picosecond lasers are safe for treating melasma in darker skin tones. Ablative fractionated lasers such as CO₂ lasers and erbium:YAG lasers also have been used in the treatment of melasma; however, there is still an extremely high risk for postinflammatory dyspigmentation 1 to 2 months after the procedure.¹⁰
• Although there is still a risk for rebound hyperpigmentation after laser treatment, use of topical hydroquinone pretreatment may help decrease postoperative hyperpigmentation.^1,5 Patients who are treated with the incorrect laser or overtreated may develop postinflammatory hyperpigmentation, rebound hyperpigmentation, or hypopigmentation.

Health disparity highlight

Melasma, most common in patients with skin of color, is a common chronic pigmentation disorder that is cosmetically and psychologically burdensome,¹¹ leading to decreased quality of life, emotional functioning, and self-esteem.¹² Clinicians should counsel patients and work closely on long-term management. The treatment options for melasma are considered cosmetic and may be cost prohibitive for many to cover out of pocket. Topical treatments have been found to be the most cost-effective.¹³ Some compounding pharmacies and drug discount programs provide more affordable treatment pricing; however, some patients are still unable to afford these options.

THE COMPARISON

A Melasma on the face of a Hispanic woman, with hyperpigmentation on the cheeks, bridge of the nose, and upper lip.

B Melasma on the face of a Malaysian woman, with hyperpigmentation on the upper cheeks and bridge of the nose.

C Melasma on the face of an African woman, with hyperpigmentation on the upper cheeks and lateral to the eyes.

Melasma (also known as chloasma) is a pigmentary disorder that causes chronic symmetric hyperpigmentation on the face. In patients with darker skin tones, centrofacial areas are affected.¹ Increased deposition of melanin distributed in the dermis leads to dermal melanosis. Newer research suggests that mast cell and keratinocyte interactions, altered gene regulation, neovascularization, and disruptions in the basement membrane cause melasma.² Patients present with epidermal or dermal melasma or a combination of both (mixed melasma).³ Wood lamp examination is helpful to distinguish between epidermal and dermal melasma. Dermal and mixed melasma can be difficult to treat and require multimodal treatments.

Epidemiology

Melasma commonly affects women ages 20 to 40 years,⁴ with a female to male ratio of 9:1.⁵ Potential triggers of melasma include hormones (eg, pregnancy, oral contraceptives, hormone replacement therapy) and exposure to UV light.^2,5 Melasma occurs in patients of all racial and ethnic backgrounds; however, the prevalence is higher in patients with darker skin tones.²

Key clinical features in people with darker skin tones

Melasma commonly manifests as symmetrically distributed, reticulated (lacy), dark brown to grayish brown patches on the cheeks, nose, forehead, upper lip, and chin in patients with darker skin tones.⁵ The pigment can be tan brown in patients with lighter skin tones. Given that postinflammatory hyperpigmentation and other pigmentary disorders can cause a similar appearance, a biopsy sometimes is needed to confirm the diagnosis, but melasma is diagnosed via physical examination in most patients. Melasma can be misdiagnosed as postinflammatory hyperpigmentation, solar lentigines, exogenous ochronosis, and Hori nevus.⁵

Worth noting

Prevention

• Daily sunscreen use is critical to prevent worsening of melasma. Sunscreen may not appear cosmetically elegant on darker skin tones, which creates a barrier to its use.⁶ Protection from both sunlight and visible light is necessary. Visible light, including light from light bulbs and device-emitted blue light, can worsen melasma. Iron oxides in tinted sunscreen offer protection from visible light.
• Physicians can recommend sunscreens that are more transparent or tinted for a better cosmetic match.
• Severe flares of melasma can occur with sun exposure despite good control with medications and laser modalities.

Treatment

• First-line therapies include topical hydroquinone 2% to 4%, tretinoin, azelaic acid, kojic acid, or ascorbic acid (vitamin C). A popular topical compound is a steroid, tretinoin, and hydroquinone.^1,5 Over-the-counter hydroquinone has been removed from the market due to safety concerns; however, it is still first line in the treatment of melasma. If hydroquinone is prescribed, treatment intervals of 6 to 8 weeks followed by a hydroquinone-free period is advised to reduce the risk for exogenous ochronosis (a paradoxical darkening of the skin).
• Chemical peels are second-line treatments that are effective for melasma. Improvement in epidermal melasma has been shown with chemical peels containing Jessner solution, salicylic acid, or a-hydroxy acid. Patients with dermal and mixed melasma have seen improvement with trichloroacetic acid 25% to 35% with or without Jessner solution.¹
• Cysteamine is a topical treatment created from the degradation of coenzyme A. It disrupts the synthesis of melanin to create a more even skin tone. It may be recommended in combination with sunscreen as a first-line or secondline topical therapy.
• Oral tranexamic acid is a third-line treatment that is an analogue for lysine. It decreases prostaglandin production, which leads to a lower number of tyrosine precursors available for the creation of melanin. Tranexamic acid has been shown to lighten the appearance of melasma.⁷ The most common and dangerous adverse effect of tranexamic acid is blood clots, and this treatment should be avoided in those on combination (estrogen and progestin) contraceptives or those with a personal or family history of clotting disorders.⁸
• Fourth-line treatments such as lasers (performed by dermatologists) can destroy the deposition of pigment while avoiding destruction of epidermal keratinocytes.^1,9,10 They also are commonly employed in refractive melasma. The most common lasers are nonablative fractionated lasers and low-fluence Q-switched lasers. The Q-switched Nd:YAG and picosecond lasers are safe for treating melasma in darker skin tones. Ablative fractionated lasers such as CO₂ lasers and erbium:YAG lasers also have been used in the treatment of melasma; however, there is still an extremely high risk for postinflammatory dyspigmentation 1 to 2 months after the procedure.¹⁰
• Although there is still a risk for rebound hyperpigmentation after laser treatment, use of topical hydroquinone pretreatment may help decrease postoperative hyperpigmentation.^1,5 Patients who are treated with the incorrect laser or overtreated may develop postinflammatory hyperpigmentation, rebound hyperpigmentation, or hypopigmentation.

Health disparity highlight

Melasma, most common in patients with skin of color, is a common chronic pigmentation disorder that is cosmetically and psychologically burdensome,¹¹ leading to decreased quality of life, emotional functioning, and self-esteem.¹² Clinicians should counsel patients and work closely on long-term management. The treatment options for melasma are considered cosmetic and may be cost prohibitive for many to cover out of pocket. Topical treatments have been found to be the most cost-effective.¹³ Some compounding pharmacies and drug discount programs provide more affordable treatment pricing; however, some patients are still unable to afford these options.

THE CASE

An 85-year-old woman with hypertension presented to our hospital with a 10-month history of insomnia along with abdominal discomfort. Several months prior, the patient had undergone an esophagogastroduodenoscopy, the results of which were normal, and had received diagnoses of psychogenic insomnia and abdominal pain from her previous physician. At that time, she was prescribed eszopiclone, but her insomnia did not improve. She did not complain of any other gastrointestinal symptoms.

On examination at our hospital, the patient’s abdomen was soft and nontender. Laboratory results were unremarkable. Abdominal computed tomography was performed to exclude obvious malignancy and showed no remarkable findings.

Additional history taking and physical examination were performed. The patient reported that she could sleep for only about 2 hours per night due to persistent severe discomfort around the umbilicus, which she described as “itching.” The discomfort occurred along with an urge to move while she laid in a state of relaxed wakefulness. This discomfort occurred no matter what position she laid in and improved if she walked or tapped around the umbilicus for a while. She denied any unusual or uncomfortable sensations in her lower extremities.

Her symptoms were absent during the daytime and not related to diet. Furthermore, she did not have any symptoms of anxiety and/or depression; a detailed neurologic examination, including cognitive assessment and extrapyramidal system, yielded unremarkable findings. Additional laboratory tests showed a mild iron deficiency (ferritin, 52.6 µ g/L; iron, 10.7 µ mol/L) without anemia.

THE DIAGNOSIS

Given the patient’s presentation and clinical history, the differential diagnosis included restless abdomen (which is a spectrum or a phenotypic variant of restless legs syndrome [RLS]) and its mimics, which include fibromyalgia and gastrointestinal tract diseases. We considered the characteristic symptoms of this case (ie, irresistible symptoms, lengthy duration of symptoms, and sleep problems) to better support the diagnosis of restless abdomen than its mimics.¹ In particular, abdominal discomfort that led to insomnia was characteristic of restless abdomen, helping to pinpoint the diagnosis.

DISCUSSION

RLS is a common sensorimotor disorder that is characterized by an unpleasant urge to move the legs.² RLS may manifest as an idiopathic condition, or it can be secondary to medical conditions such as iron deficiency and Parkinson disease.^3,4 Because the unpleasant symptom is exacerbated in the evenings, patients with RLS frequently complain of sleep disturbance.

Cases of RLS-like sensory disorders, with symptoms involving sites other than the lower extremities (eg, arms, mouth, trunk, and genitals) recently have been reported.^5-7 Among them is restless abdomen, a rare disorder that manifests with a restless abdominal sensation and worsens the quality of sleep and life.⁶

Continue to: Restless abdomen meets all...

Restless abdomen meets all other diagnostic criteria for RLS except for the affected anatomy.^6,8 In most cases of restless abdomen, the uncomfortable sensation involves the abdomen, as well as other parts of the body (eg, legs and arms). Cases in which the symptoms are confined to the abdomen are rare, with only 7 reported to date. ^6,8-10 All of these cases have involved patients older than 40 years. ^6,8-10

Treatment is straightforward, but consider iron supplementation, as well

Because RLS or its variants degrade the quality of life and sleep in patients,^3,4 appropriate therapy must be initiated early. Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—specifically, pramipexole—has been used successfully in almost all cases.^6,8-10

Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—pramipexole—has been used successfully in almost all cases.

Previous clinical research has shown that patients with RLS have low levels of iron in the brain and may benefit from iron supplementation, even if they are not anemic.^3,4 Iron replacement is suggested for patients with RLS whose fasting serum ferritin level is ≤ 75 µg/L.⁴ It is not known to what extent iron deficiency is involved in the pathophysiology of restless abdomen, and further research is required to determine the optimal therapy for it.

Our patient was started on oral supplementation with sodium ferrous citrate (50 mg/d) based on an initial suspicion that iron deficiency was the cause of her restless abdomen. We also suggested that the patient undergo a fecal occult blood test or colonoscopy, but she declined because of her advanced age.

After 2 months of iron supplementation, the patient’s serum ferritin levels improved (100 µg/L) and her insomnia and abdominal discomfort improved a bit. However, 3 months after starting on the iron supplementation, her symptoms flared again.

Continue to: We then prescribed...

We then prescribed pramipexole 0.25 mg/d. The patient’s symptoms subsequently resolved, and she no longer experienced insomnia. This favorable response to dopamine agonist therapy supported the diagnosis of restless abdomen. The patient continues to take the pramipexole to prevent a relapse.

THE TAKEAWAY

Insomnia is a common presenting complaint in primary care and sleeping pills may be prescribed without adequate investigation of the cause. However, some patients may have serious underlying diseases.¹¹

Although restless abdomen is a disorder that causes severe sleep disturbance and impairs the patient’s quality of sleep and life, it is not widely recognized by clinicians and may be misdiagnosed. When recognized, insomnia due to restless abdomen can be relieved by a simple therapy: oral dopamine agonists. Therefore, primary care physicians should consider restless abdomen as a potential cause of insomnia with abdominal symptoms.

CORRESPONDENCE
Hirohisa Fujikawa, MD, Department of Medical Education Studies, International Research Center for Medical Education, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; hirohisa.fujikawa@gmail.com

THE CASE

An 85-year-old woman with hypertension presented to our hospital with a 10-month history of insomnia along with abdominal discomfort. Several months prior, the patient had undergone an esophagogastroduodenoscopy, the results of which were normal, and had received diagnoses of psychogenic insomnia and abdominal pain from her previous physician. At that time, she was prescribed eszopiclone, but her insomnia did not improve. She did not complain of any other gastrointestinal symptoms.

On examination at our hospital, the patient’s abdomen was soft and nontender. Laboratory results were unremarkable. Abdominal computed tomography was performed to exclude obvious malignancy and showed no remarkable findings.

Additional history taking and physical examination were performed. The patient reported that she could sleep for only about 2 hours per night due to persistent severe discomfort around the umbilicus, which she described as “itching.” The discomfort occurred along with an urge to move while she laid in a state of relaxed wakefulness. This discomfort occurred no matter what position she laid in and improved if she walked or tapped around the umbilicus for a while. She denied any unusual or uncomfortable sensations in her lower extremities.

Her symptoms were absent during the daytime and not related to diet. Furthermore, she did not have any symptoms of anxiety and/or depression; a detailed neurologic examination, including cognitive assessment and extrapyramidal system, yielded unremarkable findings. Additional laboratory tests showed a mild iron deficiency (ferritin, 52.6 µ g/L; iron, 10.7 µ mol/L) without anemia.

THE DIAGNOSIS

Given the patient’s presentation and clinical history, the differential diagnosis included restless abdomen (which is a spectrum or a phenotypic variant of restless legs syndrome [RLS]) and its mimics, which include fibromyalgia and gastrointestinal tract diseases. We considered the characteristic symptoms of this case (ie, irresistible symptoms, lengthy duration of symptoms, and sleep problems) to better support the diagnosis of restless abdomen than its mimics.¹ In particular, abdominal discomfort that led to insomnia was characteristic of restless abdomen, helping to pinpoint the diagnosis.

DISCUSSION

RLS is a common sensorimotor disorder that is characterized by an unpleasant urge to move the legs.² RLS may manifest as an idiopathic condition, or it can be secondary to medical conditions such as iron deficiency and Parkinson disease.^3,4 Because the unpleasant symptom is exacerbated in the evenings, patients with RLS frequently complain of sleep disturbance.

Cases of RLS-like sensory disorders, with symptoms involving sites other than the lower extremities (eg, arms, mouth, trunk, and genitals) recently have been reported.^5-7 Among them is restless abdomen, a rare disorder that manifests with a restless abdominal sensation and worsens the quality of sleep and life.⁶

Continue to: Restless abdomen meets all...

Restless abdomen meets all other diagnostic criteria for RLS except for the affected anatomy.^6,8 In most cases of restless abdomen, the uncomfortable sensation involves the abdomen, as well as other parts of the body (eg, legs and arms). Cases in which the symptoms are confined to the abdomen are rare, with only 7 reported to date. ^6,8-10 All of these cases have involved patients older than 40 years. ^6,8-10

Treatment is straightforward, but consider iron supplementation, as well

Because RLS or its variants degrade the quality of life and sleep in patients,^3,4 appropriate therapy must be initiated early. Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—specifically, pramipexole—has been used successfully in almost all cases.^6,8-10

Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—pramipexole—has been used successfully in almost all cases.

Previous clinical research has shown that patients with RLS have low levels of iron in the brain and may benefit from iron supplementation, even if they are not anemic.^3,4 Iron replacement is suggested for patients with RLS whose fasting serum ferritin level is ≤ 75 µg/L.⁴ It is not known to what extent iron deficiency is involved in the pathophysiology of restless abdomen, and further research is required to determine the optimal therapy for it.

Our patient was started on oral supplementation with sodium ferrous citrate (50 mg/d) based on an initial suspicion that iron deficiency was the cause of her restless abdomen. We also suggested that the patient undergo a fecal occult blood test or colonoscopy, but she declined because of her advanced age.

After 2 months of iron supplementation, the patient’s serum ferritin levels improved (100 µg/L) and her insomnia and abdominal discomfort improved a bit. However, 3 months after starting on the iron supplementation, her symptoms flared again.

Continue to: We then prescribed...

We then prescribed pramipexole 0.25 mg/d. The patient’s symptoms subsequently resolved, and she no longer experienced insomnia. This favorable response to dopamine agonist therapy supported the diagnosis of restless abdomen. The patient continues to take the pramipexole to prevent a relapse.

THE TAKEAWAY

Insomnia is a common presenting complaint in primary care and sleeping pills may be prescribed without adequate investigation of the cause. However, some patients may have serious underlying diseases.¹¹

Although restless abdomen is a disorder that causes severe sleep disturbance and impairs the patient’s quality of sleep and life, it is not widely recognized by clinicians and may be misdiagnosed. When recognized, insomnia due to restless abdomen can be relieved by a simple therapy: oral dopamine agonists. Therefore, primary care physicians should consider restless abdomen as a potential cause of insomnia with abdominal symptoms.

CORRESPONDENCE
Hirohisa Fujikawa, MD, Department of Medical Education Studies, International Research Center for Medical Education, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; hirohisa.fujikawa@gmail.com

THE CASE

An 85-year-old woman with hypertension presented to our hospital with a 10-month history of insomnia along with abdominal discomfort. Several months prior, the patient had undergone an esophagogastroduodenoscopy, the results of which were normal, and had received diagnoses of psychogenic insomnia and abdominal pain from her previous physician. At that time, she was prescribed eszopiclone, but her insomnia did not improve. She did not complain of any other gastrointestinal symptoms.

On examination at our hospital, the patient’s abdomen was soft and nontender. Laboratory results were unremarkable. Abdominal computed tomography was performed to exclude obvious malignancy and showed no remarkable findings.

Additional history taking and physical examination were performed. The patient reported that she could sleep for only about 2 hours per night due to persistent severe discomfort around the umbilicus, which she described as “itching.” The discomfort occurred along with an urge to move while she laid in a state of relaxed wakefulness. This discomfort occurred no matter what position she laid in and improved if she walked or tapped around the umbilicus for a while. She denied any unusual or uncomfortable sensations in her lower extremities.

Her symptoms were absent during the daytime and not related to diet. Furthermore, she did not have any symptoms of anxiety and/or depression; a detailed neurologic examination, including cognitive assessment and extrapyramidal system, yielded unremarkable findings. Additional laboratory tests showed a mild iron deficiency (ferritin, 52.6 µ g/L; iron, 10.7 µ mol/L) without anemia.

THE DIAGNOSIS

Given the patient’s presentation and clinical history, the differential diagnosis included restless abdomen (which is a spectrum or a phenotypic variant of restless legs syndrome [RLS]) and its mimics, which include fibromyalgia and gastrointestinal tract diseases. We considered the characteristic symptoms of this case (ie, irresistible symptoms, lengthy duration of symptoms, and sleep problems) to better support the diagnosis of restless abdomen than its mimics.¹ In particular, abdominal discomfort that led to insomnia was characteristic of restless abdomen, helping to pinpoint the diagnosis.

DISCUSSION

RLS is a common sensorimotor disorder that is characterized by an unpleasant urge to move the legs.² RLS may manifest as an idiopathic condition, or it can be secondary to medical conditions such as iron deficiency and Parkinson disease.^3,4 Because the unpleasant symptom is exacerbated in the evenings, patients with RLS frequently complain of sleep disturbance.

Cases of RLS-like sensory disorders, with symptoms involving sites other than the lower extremities (eg, arms, mouth, trunk, and genitals) recently have been reported.^5-7 Among them is restless abdomen, a rare disorder that manifests with a restless abdominal sensation and worsens the quality of sleep and life.⁶

Continue to: Restless abdomen meets all...

Restless abdomen meets all other diagnostic criteria for RLS except for the affected anatomy.^6,8 In most cases of restless abdomen, the uncomfortable sensation involves the abdomen, as well as other parts of the body (eg, legs and arms). Cases in which the symptoms are confined to the abdomen are rare, with only 7 reported to date. ^6,8-10 All of these cases have involved patients older than 40 years. ^6,8-10

Treatment is straightforward, but consider iron supplementation, as well

Because RLS or its variants degrade the quality of life and sleep in patients,^3,4 appropriate therapy must be initiated early. Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—specifically, pramipexole—has been used successfully in almost all cases.^6,8-10

Although the optimal treatment strategy for restless abdomen is yet to be established, an oral dopamine agonist—pramipexole—has been used successfully in almost all cases.

Previous clinical research has shown that patients with RLS have low levels of iron in the brain and may benefit from iron supplementation, even if they are not anemic.^3,4 Iron replacement is suggested for patients with RLS whose fasting serum ferritin level is ≤ 75 µg/L.⁴ It is not known to what extent iron deficiency is involved in the pathophysiology of restless abdomen, and further research is required to determine the optimal therapy for it.

Our patient was started on oral supplementation with sodium ferrous citrate (50 mg/d) based on an initial suspicion that iron deficiency was the cause of her restless abdomen. We also suggested that the patient undergo a fecal occult blood test or colonoscopy, but she declined because of her advanced age.

After 2 months of iron supplementation, the patient’s serum ferritin levels improved (100 µg/L) and her insomnia and abdominal discomfort improved a bit. However, 3 months after starting on the iron supplementation, her symptoms flared again.

Continue to: We then prescribed...

We then prescribed pramipexole 0.25 mg/d. The patient’s symptoms subsequently resolved, and she no longer experienced insomnia. This favorable response to dopamine agonist therapy supported the diagnosis of restless abdomen. The patient continues to take the pramipexole to prevent a relapse.

THE TAKEAWAY

Insomnia is a common presenting complaint in primary care and sleeping pills may be prescribed without adequate investigation of the cause. However, some patients may have serious underlying diseases.¹¹

Although restless abdomen is a disorder that causes severe sleep disturbance and impairs the patient’s quality of sleep and life, it is not widely recognized by clinicians and may be misdiagnosed. When recognized, insomnia due to restless abdomen can be relieved by a simple therapy: oral dopamine agonists. Therefore, primary care physicians should consider restless abdomen as a potential cause of insomnia with abdominal symptoms.

CORRESPONDENCE
Hirohisa Fujikawa, MD, Department of Medical Education Studies, International Research Center for Medical Education, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; hirohisa.fujikawa@gmail.com

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Central retinal vein occlusion

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

 

 

Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Central retinal vein occlusion

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

 

 

Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Central retinal vein occlusion

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

 

 

Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

 

 

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

 

 

Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

 

 

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

 

 

Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

 

 

How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

 

 

Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; firnhaberj@ecu.edu

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

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Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The patient’s recurrent indurated nodules under her arms and other intertriginous areas, often draining pus, are consistent with a diagnosis of hidradenitis suppurativa (HS).

HS is a chronic inflammatory and suppurative skin condition that primarily involves the sweat glands.¹ The most commonly affected sites are intertriginous areas that include the axillae, groin, and perianal and inframammary regions.² Prevalence of this disorder ranges from 0.05% to 4.1% of the population with an onset from puberty to adulthood, usually at around 40 years of age.³ Its incidence is twice as high in women as men and is more common in Black individuals.^4,5

While its pathogenesis is not fully understood, it’s believed that excess proliferation of keratinocytes contributes to occlusion, leading to plugging of hair follicle ducts. Hormones, smoking, and obesity may contribute to and exacerbate HS. Intertriginous areas are prone to friction, leading to inflammation and further clogging.

The inflammation evolves into a chronic foreign body-type granulomatous inflammation with the potential for rupture, tunneling, and draining sinuses, which, although malodorous, are sterile, separating HS from an infected abscess.⁵ The result is thick, dense, scarred tissue.

The diagnosis is clinical in nature, with the history and physical exam distinguishing it from other skin disorders. In addition to the recurring physical pain, there is the emotional distress and self-consciousness about the drainage, odor, and scarring. This particular patient said that she avoided wearing sleeveless shirts due to the lesions’ appearance.

Treatment is multifactorial. Smoking and obesity are contributory factors, so smoking cessation and weight loss are recommended. For very mild HS, topical clindamycin 1% twice daily may suffice, but usually, due to the amount of inflammation, oral antibiotics are the initial therapy. (The use of antibiotics is for their anti-inflammatory component, as the nodules and unruptured tracts are sterile.)

Doxycycline 100 mg twice daily is the usual starting systemic antibiotic. In more severe or resistant cases, a combination of clindamycin and rifampin 300 mg each twice daily is used. (Worth noting: Rifampin interacts with oral contraceptives and many of these patients are women of reproductive age.) Treatment length is usually long (10 to 12 weeks) and recurrence is common.³

Spironolactone 100 mg daily and metformin 1000 mg extended release daily, which reduces insulin resistance, may be helpful. Intralesional injections of 10 mg/mL of triamcinolone in sterile saline can relieve the painful inflamed tracts. Referral for biologic agents, including infliximab, may be needed in severe cases that do not respond to other measures. Although invasive, wide debridement of the diseased tissue can reduce the disease burden.⁶

This particular patient said that she’d stopped smoking 3 years earlier and would work on losing weight. She was prescribed topical clindamycin 1% lotion twice daily along with oral clindamycin and rifampin dosed as above for 3 months. She declined metformin and intralesional injections. At a follow-up appointment 3 weeks later, she was pleased with the decrease in inflammation and had only 1 remaining tender area of fluctuance. She again declined injections and planned to continue on her oral and topical antibiotics.

‌

Photo courtesy of Daniel Stulberg, MD, FAAFP. Text courtesy of Derissa F. Raynold, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.