Tobacco companies are marketing a new version of cigarettes dubbed heat-not-burn (HNB) cigarettes.^1,2 Offered as a “modified-risk tobacco product,” HNB cigarettes utilize a lithium battery-powered heating element and are available all over the world.^1,2 Like conventional smokes, they contain tobacco, but deliver nicotine by heating leaves at 350° C rather than burning them at 600° C.^1-3 Heating the tobacco produces an inhalable aerosol with tobacco flavor and nicotine, without smoke. These HNB cigarettes are also different from e-cigarettes that aerosolize a liquid.

Heat-not-burn aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.

Tobacco companies contend that HNB cigarettes are safer than smoking tobacco.¹ Consumers inhale a heated tobacco aerosol that reportedly contains less nicotine and fewer toxicities; yet, HNB are not independently substantiated as being healthier, nor proven safe.^1-5 Thermal decomposition, rather than combustion, may afford a less dangerous nicotine consumption; however, HNB aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.^2-6 Despite possible harm reduction in the short-run, long-term safety remains unconfirmed.

Safety in passive environmental inhalations is not established.² HNB cigarettes are contraindicated during pregnancy and/or lactation. Nicotine is provided in addictive quantities, enough to foster continued dependence. Exposure to HNB products can promote longer-term usage or lead to smoking traditional tobacco cigarettes. There is also an increased risk to non-smokers of exposure to HNB aerosols. Additionally, lithium batteries have been known to burn or explode. HNB devices may even lead to privacy concerns due micro-controller chips contained within that harvest information. These chips could inform manufacturers about device usage.⁷

Tobacco is a global health hazard and smoking is the number one preventable cause of disease.^1,5,8 Global smoking prevalence is nearing 19%.⁹ There are concerns about dual use, rather than HNB cigarettes alone as a substitute for conventional smoking. The ultimate hope is to abstain from all tobacco and nicotine. Although HNB inhalations contain fewer toxic chemicals than by smoking, evidence regarding mitigation of tobacco-related diseases is inconclusive.¹⁰

Physicians have an obligation to minimize tobacco and nicotine-related hazards.

Physicians have an obligation to minimize tobacco and nicotine-related hazards. Ongoing research and clinical exposure might better document the health impact of HNB cigarettes. Until the risks and benefits of HNB cigarettes are confirmed, health care professionals would be wise to counsel against their use.

Diksha Mohanty, MD; Steven Lippmann, MD
Louisville, Ky

Tobacco companies are marketing a new version of cigarettes dubbed heat-not-burn (HNB) cigarettes.^1,2 Offered as a “modified-risk tobacco product,” HNB cigarettes utilize a lithium battery-powered heating element and are available all over the world.^1,2 Like conventional smokes, they contain tobacco, but deliver nicotine by heating leaves at 350° C rather than burning them at 600° C.^1-3 Heating the tobacco produces an inhalable aerosol with tobacco flavor and nicotine, without smoke. These HNB cigarettes are also different from e-cigarettes that aerosolize a liquid.

Heat-not-burn aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.

Tobacco companies contend that HNB cigarettes are safer than smoking tobacco.¹ Consumers inhale a heated tobacco aerosol that reportedly contains less nicotine and fewer toxicities; yet, HNB are not independently substantiated as being healthier, nor proven safe.^1-5 Thermal decomposition, rather than combustion, may afford a less dangerous nicotine consumption; however, HNB aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.^2-6 Despite possible harm reduction in the short-run, long-term safety remains unconfirmed.

Safety in passive environmental inhalations is not established.² HNB cigarettes are contraindicated during pregnancy and/or lactation. Nicotine is provided in addictive quantities, enough to foster continued dependence. Exposure to HNB products can promote longer-term usage or lead to smoking traditional tobacco cigarettes. There is also an increased risk to non-smokers of exposure to HNB aerosols. Additionally, lithium batteries have been known to burn or explode. HNB devices may even lead to privacy concerns due micro-controller chips contained within that harvest information. These chips could inform manufacturers about device usage.⁷

Tobacco is a global health hazard and smoking is the number one preventable cause of disease.^1,5,8 Global smoking prevalence is nearing 19%.⁹ There are concerns about dual use, rather than HNB cigarettes alone as a substitute for conventional smoking. The ultimate hope is to abstain from all tobacco and nicotine. Although HNB inhalations contain fewer toxic chemicals than by smoking, evidence regarding mitigation of tobacco-related diseases is inconclusive.¹⁰

Physicians have an obligation to minimize tobacco and nicotine-related hazards.

Physicians have an obligation to minimize tobacco and nicotine-related hazards. Ongoing research and clinical exposure might better document the health impact of HNB cigarettes. Until the risks and benefits of HNB cigarettes are confirmed, health care professionals would be wise to counsel against their use.

Diksha Mohanty, MD; Steven Lippmann, MD
Louisville, Ky

Tobacco companies are marketing a new version of cigarettes dubbed heat-not-burn (HNB) cigarettes.^1,2 Offered as a “modified-risk tobacco product,” HNB cigarettes utilize a lithium battery-powered heating element and are available all over the world.^1,2 Like conventional smokes, they contain tobacco, but deliver nicotine by heating leaves at 350° C rather than burning them at 600° C.^1-3 Heating the tobacco produces an inhalable aerosol with tobacco flavor and nicotine, without smoke. These HNB cigarettes are also different from e-cigarettes that aerosolize a liquid.

Heat-not-burn aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.

Tobacco companies contend that HNB cigarettes are safer than smoking tobacco.¹ Consumers inhale a heated tobacco aerosol that reportedly contains less nicotine and fewer toxicities; yet, HNB are not independently substantiated as being healthier, nor proven safe.^1-5 Thermal decomposition, rather than combustion, may afford a less dangerous nicotine consumption; however, HNB aerosols deliver many of the same dangerous compounds as traditional cigarettes, including carbon monoxide, tar, and aromatic hydrocarbons.^2-6 Despite possible harm reduction in the short-run, long-term safety remains unconfirmed.

Safety in passive environmental inhalations is not established.² HNB cigarettes are contraindicated during pregnancy and/or lactation. Nicotine is provided in addictive quantities, enough to foster continued dependence. Exposure to HNB products can promote longer-term usage or lead to smoking traditional tobacco cigarettes. There is also an increased risk to non-smokers of exposure to HNB aerosols. Additionally, lithium batteries have been known to burn or explode. HNB devices may even lead to privacy concerns due micro-controller chips contained within that harvest information. These chips could inform manufacturers about device usage.⁷

Tobacco is a global health hazard and smoking is the number one preventable cause of disease.^1,5,8 Global smoking prevalence is nearing 19%.⁹ There are concerns about dual use, rather than HNB cigarettes alone as a substitute for conventional smoking. The ultimate hope is to abstain from all tobacco and nicotine. Although HNB inhalations contain fewer toxic chemicals than by smoking, evidence regarding mitigation of tobacco-related diseases is inconclusive.¹⁰

Physicians have an obligation to minimize tobacco and nicotine-related hazards.

Physicians have an obligation to minimize tobacco and nicotine-related hazards. Ongoing research and clinical exposure might better document the health impact of HNB cigarettes. Until the risks and benefits of HNB cigarettes are confirmed, health care professionals would be wise to counsel against their use.

Diksha Mohanty, MD; Steven Lippmann, MD
Louisville, Ky

Like JFP’s Editor-in-Chief, Dr. John Hickner, I have been skeptical about bariatric surgery (A [former] skeptic’s view of bariatric surgery. J Fam Pract. 2018;67:600), but I will recommend it for a select few patients who are unable or unwilling to undergo significant lifestyle changes. My experience in clinic has done nothing to change this skeptical view. I have many patients who opted for bariatric surgery, but did not change their lifestyle habits. These patients often regain weight and accumulate chronic diseases 2 to 7 years postop. In the end, if a patient does not change their lifestyle, bariatric surgery can push the consequences of obesity out 5 to 10 years, but at a very significant risk.

The most significant problem I see is that many primary care providers do not feel qualified to impart meaningful lifestyle recommendations to patients, which often leads to guidance that is inadequate and, in some cases, inaccurate. Furthermore, assuming patients have received evidence-based instructions, they often lack the support and means to apply these lifestyle changes. I would be very hesitant to recommend bariatric surgery before addressing all of these concerns.

An interesting study done by Lingvay et al¹ showed that postsurgical starvation (600 kcal/d) without the bariatric surgery had better short-term outcomes than surgery with calorie restriction, which suggests that a period of starvation is better than surgery.

It is more prudent to refer bariatric surgery candidates to someone who understands good nutrition and lifestyle changes.

In general, the results of evidence-based lifestyle changes far surpass any medical or surgical treatment for obesity and its associated chronic diseases. The evidence for this is overwhelming. (See books by Drs. Joel Fuhrman, Michael Greger, Neal Barnard, Dean Ornish, and Garth Davis, as well as the hundreds of peer-reviewed studies cited in these books.) Yet most patients under-going bariatric surgery never receive proper instructions or attempt any meaningful lifestyle changes.

I think it is far more prudent to refer potential surgical candidates to someone who understands good nutrition and lifestyle changes, such as a doctor certified by the American College of Lifestyle Medicine (lifestylemedicine.org). Surgery, in my opinion, is a very poor and dangerous second choice.

John Reed, MD
Fishersville, Va

Like JFP’s Editor-in-Chief, Dr. John Hickner, I have been skeptical about bariatric surgery (A [former] skeptic’s view of bariatric surgery. J Fam Pract. 2018;67:600), but I will recommend it for a select few patients who are unable or unwilling to undergo significant lifestyle changes. My experience in clinic has done nothing to change this skeptical view. I have many patients who opted for bariatric surgery, but did not change their lifestyle habits. These patients often regain weight and accumulate chronic diseases 2 to 7 years postop. In the end, if a patient does not change their lifestyle, bariatric surgery can push the consequences of obesity out 5 to 10 years, but at a very significant risk.

The most significant problem I see is that many primary care providers do not feel qualified to impart meaningful lifestyle recommendations to patients, which often leads to guidance that is inadequate and, in some cases, inaccurate. Furthermore, assuming patients have received evidence-based instructions, they often lack the support and means to apply these lifestyle changes. I would be very hesitant to recommend bariatric surgery before addressing all of these concerns.

An interesting study done by Lingvay et al¹ showed that postsurgical starvation (600 kcal/d) without the bariatric surgery had better short-term outcomes than surgery with calorie restriction, which suggests that a period of starvation is better than surgery.

It is more prudent to refer bariatric surgery candidates to someone who understands good nutrition and lifestyle changes.

In general, the results of evidence-based lifestyle changes far surpass any medical or surgical treatment for obesity and its associated chronic diseases. The evidence for this is overwhelming. (See books by Drs. Joel Fuhrman, Michael Greger, Neal Barnard, Dean Ornish, and Garth Davis, as well as the hundreds of peer-reviewed studies cited in these books.) Yet most patients under-going bariatric surgery never receive proper instructions or attempt any meaningful lifestyle changes.

I think it is far more prudent to refer potential surgical candidates to someone who understands good nutrition and lifestyle changes, such as a doctor certified by the American College of Lifestyle Medicine (lifestylemedicine.org). Surgery, in my opinion, is a very poor and dangerous second choice.

John Reed, MD
Fishersville, Va

Like JFP’s Editor-in-Chief, Dr. John Hickner, I have been skeptical about bariatric surgery (A [former] skeptic’s view of bariatric surgery. J Fam Pract. 2018;67:600), but I will recommend it for a select few patients who are unable or unwilling to undergo significant lifestyle changes. My experience in clinic has done nothing to change this skeptical view. I have many patients who opted for bariatric surgery, but did not change their lifestyle habits. These patients often regain weight and accumulate chronic diseases 2 to 7 years postop. In the end, if a patient does not change their lifestyle, bariatric surgery can push the consequences of obesity out 5 to 10 years, but at a very significant risk.

The most significant problem I see is that many primary care providers do not feel qualified to impart meaningful lifestyle recommendations to patients, which often leads to guidance that is inadequate and, in some cases, inaccurate. Furthermore, assuming patients have received evidence-based instructions, they often lack the support and means to apply these lifestyle changes. I would be very hesitant to recommend bariatric surgery before addressing all of these concerns.

An interesting study done by Lingvay et al¹ showed that postsurgical starvation (600 kcal/d) without the bariatric surgery had better short-term outcomes than surgery with calorie restriction, which suggests that a period of starvation is better than surgery.

It is more prudent to refer bariatric surgery candidates to someone who understands good nutrition and lifestyle changes.

In general, the results of evidence-based lifestyle changes far surpass any medical or surgical treatment for obesity and its associated chronic diseases. The evidence for this is overwhelming. (See books by Drs. Joel Fuhrman, Michael Greger, Neal Barnard, Dean Ornish, and Garth Davis, as well as the hundreds of peer-reviewed studies cited in these books.) Yet most patients under-going bariatric surgery never receive proper instructions or attempt any meaningful lifestyle changes.

I think it is far more prudent to refer potential surgical candidates to someone who understands good nutrition and lifestyle changes, such as a doctor certified by the American College of Lifestyle Medicine (lifestylemedicine.org). Surgery, in my opinion, is a very poor and dangerous second choice.

John Reed, MD
Fishersville, Va

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

I appreciated the PURL, “Should you reassess your patient’s asthma diagnosis?” (J Fam Pract. 2018;67:704-707) that reminded clinicians to taper asthma controller medications in asymptomatic patients. The articles cited^1,2 by Drs. Stevermer and Hayes documented that one-third of the adults enrolled in the respective study with physician-diagnosed asthma did not have objective evidence for asthma and were either over-diagnosed or had remitted. These articles also contained evidence that: 1) over-diagnosis was likely much more common than remission,¹ and 2) there was a significant temporal trend towards increasing over-diagnosis/remission during the last several decades. The authors of the cited article¹ suggested that the temporal trend could be explained by increased public awareness of respiratory symptoms, more aggressive marketing of asthma medications, and a lack of objective measurement of reversible airway obstruction in primary care. These assertions deserve careful consideration as we strive to diagnose asthma appropriately.

Over-diagnosis/remission is almost certainly not as prevalent (33%) as the authors of the cited articles^1,2 reported. The reason is simple selection bias: 1) the cited study² excluded asthma patients who smoked >10 pack-years (it enrolled 701 asthma patients and excluded 812 asthma patients with a >10 pack-year smoking history), and 2) this study likely did not include asthma patients with the asthma-COPD overlap syndrome, which is treated as asthma and comprises an additional 30% of our patients with chronic airflow limitation (the asthma-COPD spectrum).³ Asthma patients who smoke and/or have the overlap syndrome are prone to severe asthma that is refractory to inhaled corticosteroids.^3,4

In addition to making the correct diagnosis, it is equally important to be aware of efficacious therapies for severe refractory asthma that primary care clinicians can easily use. There is now good evidence that azithromycin is efficacious for severe refractory asthma⁵ and should be considered prior to referral for immunomodulatory asthma therapies.⁶

David L. Hahn, MD, MS
Madison, Wis

1. Aaron SD, Vandemheen KL, Boulet LP, et al; Canadian Respiratory Clinical Research Consortium. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

3. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax. 2009;64:728-735.

4. Stapleton M, Howard-Thompson A, George C, et al. Smoking and asthma. J Am Board Fam Med. 2011;24;313-322.

5. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017:390659-668.

6. Hahn DL, Grasmick M, Hetzel S, et al; AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study Group. Azithromycin for bronchial asthma in adults: an effectiveness trial. J Am Board Fam Med. 2012;25:442-459.

Continue to: Authors' response...

Authors’ response:

We appreciate Dr. Hahn’s observations about the PURL¹ on overdiagnosis of asthma. This article focused on the results of a prospective, multicenter cohort study² that evaluated the feasibility of tapering, and in many patients, stopping asthma medications. We agree that if the study had included people diagnosed with asthma who also had smoked at least 10 pack-years or who also had COPD, the proportion of those who would eventually no longer meet diagnostic criteria for asthma would be lower than in this study. We are uncertain of the relative proportion of cases that were overdiagnosis, when compared with true remission of disease, as only 43% of those no longer meeting the diagnostic criteria for asthma had evidence of prior lung function testing, whether by formal spirometry, serial peak function testing, or bronchial challenge testing.

We agree that using efficacious therapies for severe refractory asthma is essential, but the selection of those therapies was outside the scope of this PURL.

James J. Stevermer, MD, MSPH; Alisa Hayes, MD
Columbia, Mo

1. Stevermer JJ, Hayes A. Should you reassess your patient’s asthma diagnosis? J Fam Pract. 2018;67:704-707.

2. Aaron SD, Vandemheen KL, FitzGerald JM, et al; Canadian Respiratory Research Network. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.

EVIDENCE SUMMARY

A 2017 network meta-analysis included 19 RCTs and 87,831 patients receiving anticoagulation, antiplatelet therapy, or LAAC for NVAF.¹ LAAC was superior to antiplatelet therapy (hazard ratio [HR]=0.44; 95% confidence interval [CI], 0.23-0.86; P<.05) and similar to NOACs (HR=1.01; 95% CI, 0.53-1.92; P=.969) for reducing risk of stroke.

LAAC and NOACs found “most effective”

A network meta-analysis of 21 RCTs, which included data from 96,017 patients, examined the effectiveness of 7 interventions to prevent stroke in patients with NVAF: 4 NOACs, VKA, aspirin, and LAAC; the analysis compared VKA with the other interventions.² The 2 trials that investigated LAAC accounted for only 1114 patients.

When the 7 interventions were ranked simultaneously on 2 efficacy outcomes (stroke/systemic embolism and all-cause mortality), all 4 NOACs and LAAC clustered together as “the most effective and lifesaving.”

Fewer hemorrhagic strokes with LAAC than VKA

A 2016 meta-analysis of 6 RCTs compared risk of stroke for adults with NVAF who received LAAC, VKA, or NOACs.³ No significant differences were found between NOACs and VKA or LAAC and VKA. The LAAC group had a significantly smaller number of patients.

A 2015 meta-analysis of 2406 patients with NVAF found that patients who received LAAC had significantly fewer hemorrhagic strokes (HR=0.22; P<.05) than patients who received VKA.⁴ No differences in all-cause stroke were found between the 2 groups during an average follow-up of 2.69 years.

LAAC found superior to warfarin for stroke prevention in one trial

A 2014 multicenter, randomized study (PROTECT-AF) of 707 patients with NVAF plus 1 additional stroke risk factor compared LAAC with VKA (warfarin).⁵ LAAC met criteria at 3.8 years for both noninferiority and superiority in preventing stroke, based on 2.3 events per 100 patient-years compared with 3.8 events per 100 patient-years for VKA. The number needed to treat with LAAC was 67 to result in 1 less event per patient-year.

A 2014 RCT (PREVAIL) evaluated patients with NVAF plus 1 additional stroke risk factor. LAAC was noninferior to warfarin for ischemic stroke prevention.⁶

Continue to: RECOMMENDATIONS

The American College of Cardiology (ACC) recommends LAAC for patients with NVAF who are not candidates for long-term anticoagulation.⁷ Similarly, the 2016 European Society of Cardiology guidelines issued a Class IIb recommendation for LAAC for stroke prevention in those with contraindications for long-term anticoagulation.⁸ Lastly, in a 2014 guideline, the American Heart Association, ACC, and the Heart Rhythm Society issued a Class IIb recommendation for surgical excision of the left atrial appendage in patients with atrial fibrillation undergoing cardiac surgery, but did not provide recommendations regarding LAAC.⁹

EVIDENCE SUMMARY

A 2017 network meta-analysis included 19 RCTs and 87,831 patients receiving anticoagulation, antiplatelet therapy, or LAAC for NVAF.¹ LAAC was superior to antiplatelet therapy (hazard ratio [HR]=0.44; 95% confidence interval [CI], 0.23-0.86; P<.05) and similar to NOACs (HR=1.01; 95% CI, 0.53-1.92; P=.969) for reducing risk of stroke.

LAAC and NOACs found “most effective”

A network meta-analysis of 21 RCTs, which included data from 96,017 patients, examined the effectiveness of 7 interventions to prevent stroke in patients with NVAF: 4 NOACs, VKA, aspirin, and LAAC; the analysis compared VKA with the other interventions.² The 2 trials that investigated LAAC accounted for only 1114 patients.

When the 7 interventions were ranked simultaneously on 2 efficacy outcomes (stroke/systemic embolism and all-cause mortality), all 4 NOACs and LAAC clustered together as “the most effective and lifesaving.”

Fewer hemorrhagic strokes with LAAC than VKA

A 2016 meta-analysis of 6 RCTs compared risk of stroke for adults with NVAF who received LAAC, VKA, or NOACs.³ No significant differences were found between NOACs and VKA or LAAC and VKA. The LAAC group had a significantly smaller number of patients.

A 2015 meta-analysis of 2406 patients with NVAF found that patients who received LAAC had significantly fewer hemorrhagic strokes (HR=0.22; P<.05) than patients who received VKA.⁴ No differences in all-cause stroke were found between the 2 groups during an average follow-up of 2.69 years.

LAAC found superior to warfarin for stroke prevention in one trial

A 2014 multicenter, randomized study (PROTECT-AF) of 707 patients with NVAF plus 1 additional stroke risk factor compared LAAC with VKA (warfarin).⁵ LAAC met criteria at 3.8 years for both noninferiority and superiority in preventing stroke, based on 2.3 events per 100 patient-years compared with 3.8 events per 100 patient-years for VKA. The number needed to treat with LAAC was 67 to result in 1 less event per patient-year.

A 2014 RCT (PREVAIL) evaluated patients with NVAF plus 1 additional stroke risk factor. LAAC was noninferior to warfarin for ischemic stroke prevention.⁶

Continue to: RECOMMENDATIONS

The American College of Cardiology (ACC) recommends LAAC for patients with NVAF who are not candidates for long-term anticoagulation.⁷ Similarly, the 2016 European Society of Cardiology guidelines issued a Class IIb recommendation for LAAC for stroke prevention in those with contraindications for long-term anticoagulation.⁸ Lastly, in a 2014 guideline, the American Heart Association, ACC, and the Heart Rhythm Society issued a Class IIb recommendation for surgical excision of the left atrial appendage in patients with atrial fibrillation undergoing cardiac surgery, but did not provide recommendations regarding LAAC.⁹

EVIDENCE SUMMARY

A 2017 network meta-analysis included 19 RCTs and 87,831 patients receiving anticoagulation, antiplatelet therapy, or LAAC for NVAF.¹ LAAC was superior to antiplatelet therapy (hazard ratio [HR]=0.44; 95% confidence interval [CI], 0.23-0.86; P<.05) and similar to NOACs (HR=1.01; 95% CI, 0.53-1.92; P=.969) for reducing risk of stroke.

LAAC and NOACs found “most effective”

A network meta-analysis of 21 RCTs, which included data from 96,017 patients, examined the effectiveness of 7 interventions to prevent stroke in patients with NVAF: 4 NOACs, VKA, aspirin, and LAAC; the analysis compared VKA with the other interventions.² The 2 trials that investigated LAAC accounted for only 1114 patients.

When the 7 interventions were ranked simultaneously on 2 efficacy outcomes (stroke/systemic embolism and all-cause mortality), all 4 NOACs and LAAC clustered together as “the most effective and lifesaving.”

Fewer hemorrhagic strokes with LAAC than VKA

A 2016 meta-analysis of 6 RCTs compared risk of stroke for adults with NVAF who received LAAC, VKA, or NOACs.³ No significant differences were found between NOACs and VKA or LAAC and VKA. The LAAC group had a significantly smaller number of patients.

A 2015 meta-analysis of 2406 patients with NVAF found that patients who received LAAC had significantly fewer hemorrhagic strokes (HR=0.22; P<.05) than patients who received VKA.⁴ No differences in all-cause stroke were found between the 2 groups during an average follow-up of 2.69 years.

LAAC found superior to warfarin for stroke prevention in one trial

A 2014 multicenter, randomized study (PROTECT-AF) of 707 patients with NVAF plus 1 additional stroke risk factor compared LAAC with VKA (warfarin).⁵ LAAC met criteria at 3.8 years for both noninferiority and superiority in preventing stroke, based on 2.3 events per 100 patient-years compared with 3.8 events per 100 patient-years for VKA. The number needed to treat with LAAC was 67 to result in 1 less event per patient-year.

A 2014 RCT (PREVAIL) evaluated patients with NVAF plus 1 additional stroke risk factor. LAAC was noninferior to warfarin for ischemic stroke prevention.⁶

Continue to: RECOMMENDATIONS

The American College of Cardiology (ACC) recommends LAAC for patients with NVAF who are not candidates for long-term anticoagulation.⁷ Similarly, the 2016 European Society of Cardiology guidelines issued a Class IIb recommendation for LAAC for stroke prevention in those with contraindications for long-term anticoagulation.⁸ Lastly, in a 2014 guideline, the American Heart Association, ACC, and the Heart Rhythm Society issued a Class IIb recommendation for surgical excision of the left atrial appendage in patients with atrial fibrillation undergoing cardiac surgery, but did not provide recommendations regarding LAAC.⁹

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.

When I was training to become a family physician, my mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation. I am not sure where that figure came from, but my 40 years of experience in family medicine supports that prediction. Of course, the flip-side of that coin is having the wisdom to make those referrals for patients who really need a specialist’s diagnostic or treatment skills. The “rub,” of course, is that when I do need a specialist’s help, the wait for an appointment is often unacceptably long—both for me and my patients.

One way to help alleviate the logjam of referrals is to manage more medical problems ourselves. Now I don’t mean holding on to patients who definitely need a referral. But I do think we should avoid being too quick to hand off a patient. Let me explain.

When I was Chair of Family Medicine at Cleveland Clinic, I asked my specialty colleagues what percentage of the referred patients they saw in their offices could be managed competently by a well-trained family physician. The usual answer—from a variety of specialists—was “about 30%.” If we took care of that 30% of patients ourselves, it would go a long way toward freeing up specialists’ schedules to see the patients who truly require their expertise.

My mentor often told me that a competent family physician should be able to manage about 80% of patients’ office visits without consultation.

Some public health systems, such as the University of California San Francisco Medical Center,¹ have implemented successful triage systems to alleviate the referral backlog. Patients are triaged by a specialist and assigned to 1 of 3 categories: 1) urgent—the patient will be seen right away, 2) non-urgent—the patient will be seen as soon as possible (usually within 2 weeks), or 3) phone/email consultation—the specialist provides diagnostic and management advice electronically, or by phone, but does not see the patient.

Continue to: The issue of referral comes to mind...

The issue of referral comes to mind this month in light of our cover story on migraine headache management. Migraine is one of those conditions that is often referred for specialist care, but can, in many cases, be competently managed by family physicians. The diagnosis of migraine is made almost entirely by history and physical exam, and there are many treatments for acute attacks and prevention that are effective and can be prescribed by family physicians and other primary health care professionals.

Yes, patients with more severe migraine may need a specialist consultation. But let’s remain cognizant of the fact that a good percentage of our patients will be best served staying right where they are—in the office of their family physician.

A 59-year-old woman presented to a dermatology clinic with an asymptomatic brown facial hyperpigmentation that had developed several years earlier, and had persisted, despite regular face washing. Physicians who previously treated this patient interpreted this as melasma and advised her to wear sunscreen. The condition was not aggravated by sun exposure. The patient reported that she was otherwise healthy.

Physical examination revealed a brown discoloration with a slightly rough texture. Upon rubbing the affected area with a 70% isopropyl alcohol pad, normal skin was revealed (FIGURE 1A) and brown flakes were apparent on the gauze (FIGURE 1B). 

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

The physician diagnosed terra firma-forme dermatosis (TFFD) in this patient, noting the “dirty brown coloration” and distribution that did not suggest post-inflammatory hyperpigmentation or melasma. TFFD is a rare and benign form of acquired hyperpigmentation characterized by “velvety, pigmented patches or plaques.”¹ A simple bedside test, known as an “alcohol wipe test,” both confirms and treats TFFD; it involves rubbing the affected area with a 70% isopropyl alcohol pad.¹

TFFD is not a consequence of poor hygiene, but may be a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria.

TFFD typically affects the face, neck, trunk, or ankles, but the scalp, axilla, back, and pubis also can be affected.¹ Histopathology will show negligible amounts of dermal inflammation, hyperkeratosis with mild acanthosis, and hyperkeratosis and papillomatosis.¹ Most patients diagnosed with TFFD report that the hyperpigmentation does not improve despite washing with soap and water.²

Hygiene is not a factor

In 2015, Greywal and Cohen followed the case presentations of 10 Caucasian patients with TFFD who presented with “brown and/or black plaques or papules or both.”² Many of the individuals followed in this case series reported “[practicing] good hygiene and showered a minimum of every other day or daily.”² The same was reported by the patient in this case. This suggests that TFFD is not a consequence of poor hygiene but perhaps a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria on the skin.³ This produces the hyperpigmentation seen clinically.

Differential includes post-inflammatory hyperpigmentation

Several other hyperpigmentation disorders were considered on the initial differential diagnosis for this case, including melasma and post-inflammatory hyperpigmentation. However, these 2 conditions are macular, whereas this hyperpigmented condition had a rough, mildly papular texture. Additionally, melasma flares up in the summer with UV exposure, and post-inflammatory hyperpigmentation presents with pruritus and/or a pre-existing rash.⁴ This patient reported that the condition did not itch nor change with increased sunlight, thus making melasma and post-inflammatory hyperpigmentation unlikely diagnoses.

Acanthosis nigricans also was considered because it presents with a velvety brown pigmentation similar to what was seen with this patient. Acanthosis nigricans, however, primarily affects flexural areas, not the face, making it improbable.

Continue to: Our patient

Our patient. A “wipe test” was performed on the patient. This removed the brown flaky scaling and revealed the underlying normal skin. We instructed the patient to wash daily with a soapy wash cloth and scrub with 70% isopropyl alcohol should the hyperpigmentation recur. The patient did not return.

CORRESPONDENCE
Robert T. Brodell, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; rbrodell@umc.edu

A 59-year-old woman presented to a dermatology clinic with an asymptomatic brown facial hyperpigmentation that had developed several years earlier, and had persisted, despite regular face washing. Physicians who previously treated this patient interpreted this as melasma and advised her to wear sunscreen. The condition was not aggravated by sun exposure. The patient reported that she was otherwise healthy.

Physical examination revealed a brown discoloration with a slightly rough texture. Upon rubbing the affected area with a 70% isopropyl alcohol pad, normal skin was revealed (FIGURE 1A) and brown flakes were apparent on the gauze (FIGURE 1B). 

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

The physician diagnosed terra firma-forme dermatosis (TFFD) in this patient, noting the “dirty brown coloration” and distribution that did not suggest post-inflammatory hyperpigmentation or melasma. TFFD is a rare and benign form of acquired hyperpigmentation characterized by “velvety, pigmented patches or plaques.”¹ A simple bedside test, known as an “alcohol wipe test,” both confirms and treats TFFD; it involves rubbing the affected area with a 70% isopropyl alcohol pad.¹

TFFD is not a consequence of poor hygiene, but may be a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria.

TFFD typically affects the face, neck, trunk, or ankles, but the scalp, axilla, back, and pubis also can be affected.¹ Histopathology will show negligible amounts of dermal inflammation, hyperkeratosis with mild acanthosis, and hyperkeratosis and papillomatosis.¹ Most patients diagnosed with TFFD report that the hyperpigmentation does not improve despite washing with soap and water.²

Hygiene is not a factor

In 2015, Greywal and Cohen followed the case presentations of 10 Caucasian patients with TFFD who presented with “brown and/or black plaques or papules or both.”² Many of the individuals followed in this case series reported “[practicing] good hygiene and showered a minimum of every other day or daily.”² The same was reported by the patient in this case. This suggests that TFFD is not a consequence of poor hygiene but perhaps a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria on the skin.³ This produces the hyperpigmentation seen clinically.

Differential includes post-inflammatory hyperpigmentation

Several other hyperpigmentation disorders were considered on the initial differential diagnosis for this case, including melasma and post-inflammatory hyperpigmentation. However, these 2 conditions are macular, whereas this hyperpigmented condition had a rough, mildly papular texture. Additionally, melasma flares up in the summer with UV exposure, and post-inflammatory hyperpigmentation presents with pruritus and/or a pre-existing rash.⁴ This patient reported that the condition did not itch nor change with increased sunlight, thus making melasma and post-inflammatory hyperpigmentation unlikely diagnoses.

Acanthosis nigricans also was considered because it presents with a velvety brown pigmentation similar to what was seen with this patient. Acanthosis nigricans, however, primarily affects flexural areas, not the face, making it improbable.

Continue to: Our patient

Our patient. A “wipe test” was performed on the patient. This removed the brown flaky scaling and revealed the underlying normal skin. We instructed the patient to wash daily with a soapy wash cloth and scrub with 70% isopropyl alcohol should the hyperpigmentation recur. The patient did not return.

CORRESPONDENCE
Robert T. Brodell, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; rbrodell@umc.edu

A 59-year-old woman presented to a dermatology clinic with an asymptomatic brown facial hyperpigmentation that had developed several years earlier, and had persisted, despite regular face washing. Physicians who previously treated this patient interpreted this as melasma and advised her to wear sunscreen. The condition was not aggravated by sun exposure. The patient reported that she was otherwise healthy.

Physical examination revealed a brown discoloration with a slightly rough texture. Upon rubbing the affected area with a 70% isopropyl alcohol pad, normal skin was revealed (FIGURE 1A) and brown flakes were apparent on the gauze (FIGURE 1B). 

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

The physician diagnosed terra firma-forme dermatosis (TFFD) in this patient, noting the “dirty brown coloration” and distribution that did not suggest post-inflammatory hyperpigmentation or melasma. TFFD is a rare and benign form of acquired hyperpigmentation characterized by “velvety, pigmented patches or plaques.”¹ A simple bedside test, known as an “alcohol wipe test,” both confirms and treats TFFD; it involves rubbing the affected area with a 70% isopropyl alcohol pad.¹

TFFD is not a consequence of poor hygiene, but may be a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria.

TFFD typically affects the face, neck, trunk, or ankles, but the scalp, axilla, back, and pubis also can be affected.¹ Histopathology will show negligible amounts of dermal inflammation, hyperkeratosis with mild acanthosis, and hyperkeratosis and papillomatosis.¹ Most patients diagnosed with TFFD report that the hyperpigmentation does not improve despite washing with soap and water.²

Hygiene is not a factor

In 2015, Greywal and Cohen followed the case presentations of 10 Caucasian patients with TFFD who presented with “brown and/or black plaques or papules or both.”² Many of the individuals followed in this case series reported “[practicing] good hygiene and showered a minimum of every other day or daily.”² The same was reported by the patient in this case. This suggests that TFFD is not a consequence of poor hygiene but perhaps a result of “sticky” sebum that produces a buildup of keratin debris, sebum, and bacteria on the skin.³ This produces the hyperpigmentation seen clinically.

Differential includes post-inflammatory hyperpigmentation

Several other hyperpigmentation disorders were considered on the initial differential diagnosis for this case, including melasma and post-inflammatory hyperpigmentation. However, these 2 conditions are macular, whereas this hyperpigmented condition had a rough, mildly papular texture. Additionally, melasma flares up in the summer with UV exposure, and post-inflammatory hyperpigmentation presents with pruritus and/or a pre-existing rash.⁴ This patient reported that the condition did not itch nor change with increased sunlight, thus making melasma and post-inflammatory hyperpigmentation unlikely diagnoses.

Acanthosis nigricans also was considered because it presents with a velvety brown pigmentation similar to what was seen with this patient. Acanthosis nigricans, however, primarily affects flexural areas, not the face, making it improbable.

Continue to: Our patient

Our patient. A “wipe test” was performed on the patient. This removed the brown flaky scaling and revealed the underlying normal skin. We instructed the patient to wash daily with a soapy wash cloth and scrub with 70% isopropyl alcohol should the hyperpigmentation recur. The patient did not return.

CORRESPONDENCE
Robert T. Brodell, MD, Department of Dermatology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; rbrodell@umc.edu

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; dustymarienarducci@gmail.com

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; dustymarienarducci@gmail.com

THE CASE

A 61-year-old Caucasian woman presented with acute right shoulder pain that began after she received an influenza vaccination at a local pharmacy 2 weeks earlier. She pointed to the proximal-most aspect of her lateral right upper arm as the vaccination site. Her pain intensified with shoulder abduction, forward flexion, and reaching movements. She denied recent and past injury to her shoulder, fever, chills, rash, or skin changes at the injection site. She said her left shoulder did not bother her.

The patient had continued to participate in her aerobics class, despite the discomfort. Her medical history included hypertension and myocardial infarction, and the medications she was taking included lisinopril 20 mg/d, atenolol 50 mg/d, and aspirin 81 mg/d.

The physical exam revealed a thin female with no visible rashes or erythema on her right shoulder. While there was no deltoid atrophy in comparison to her unaffected shoulder, she generally had low muscle mass in both arms. A painful arc of abduction was present, as was pain with palpation of the supraspinatus insertion. No pain was appreciated over the short or long head of the biceps tendon or the sternoclavicular or acromioclavicular joints. Strength was 5/5 for all movements of the rotator cuff, but pain was reproduced with resisted shoulder abduction. A Hawkin’s test was positive, while Speed’s, Yergason’s, cross-arm abduction, and O’Brien’s tests were all negative.

THE DIAGNOSIS

Anteroposterior, Grashey, Y-view, and axillary view radiographs of the right shoulder were normal without any calcific tendinopathy, degenerative changes, or acute fractures. The patient’s history and physical exam were consistent with a rotator cuff tendinitis secondary to an immune response to an influenza vaccination that infiltrated the supraspinatus tendon.

DISCUSSION

Soreness, redness and swelling at the injection site, fever, body aches, and headache are common adverse effects of the influenza vaccine.¹Although rare, acute brachial neuritis, infection, rotator cuff injuries, and contusions of the humeral head have also been reported. ^2-5 Collectively, these conditions are referred to as shoulder injuries related to vaccination administration (SIRVA). There have been multiple SIRVA cases reported in the United States, and the US Court of Federal Claims has compensated >100 patients for SIRVA since 2011.⁶ There is currently no listing of SIRVA as a potential adverse reaction to the influenza vaccine on the package inserts or on the Centers for Disease Control and Prevention (CDC) Web site.

Shoulder soreness lasting <72 hours without functional impairment is likely due to soreness at the injection site. If symptoms do not resolve within 72 to 96 hours, consider a more thorough workup, with SIRVA being a possible diagnosis.^1,7 The etiology of SIRVA remains uncertain, but an inflammatory reaction from a vaccine mistakenly administered into the subacromial/subdeltoid bursa has been suggested. Whether this reaction is dependent on the nonantigenic or antigenic components of the vaccine has yet to be determined.

Symptoms of SIRVA include pain with arm movement, pain that is worse at night or awakens the patient from sleep, restricted range of motion, or arm weakness. Examination will reveal pain when resisting rotator cuff movements, particularly shoulder abduction. Advanced imaging can be considered when the diagnosis is in question. In previous cases of vaccine-associated rotator cuff tendinopathy in the authors’ practice, T2 magnetic resonance imaging (MRI) has shown focal inflammatory signal within the supraspinatus tendon and subacromial bursa.

Continue to: With support from the CDC...

With support from the CDC, the Immunization Action Coalition (IAC), a source of immunization information for health care professionals, recommends that vaccines be administered into the deltoid or vastus lateralis for individuals between the ages of 3 and 18 years and recommends the deltoid as the preferred location in adults ≥19 years. The IAC suggests increasing the needle length for intramuscular (IM) immunizations (depending on the weight of the patient), although in the authors’ experience, the adjustment of needle length may often be overlooked (TABLE⁷).

The majority of reported SIRVA cases caused by overpenetration have occurred in individuals weighing <140 lb or those who had little deltoid muscle bulk. An MRI study to evaluate optimal intramuscular needle length in pediatric patients found that the IAC-recommended needle lengths still allowed penetration of the subdeltoid space in a substantial number of patients.⁸ Classic teaching of IM deltoid injection landmarks is 3 fingerbreadths distal to the acromion, and a more proximal administration of a vaccine would allow penetration of the rotator cuff structures below.

How to manage the patient

Patients who develop SIRVA should be managed similarly to patients with tendinopathy from other causes. Treatment options include: physical therapy, anti-inflammatory medications, and subacromial corticosteroid injections. Given the significant discomfort and nighttime pain associated with rotator cuff tendinopathy, corticosteroid injections can offer rapid relief.

Limited data exist on the effect of corticosteroids on the suppression of the immune response in immunocompetent patients. Vaccinations are generally thought to stimulate an adequate immune response 14 days following administration, so our suggestion would be to re-vaccinate patients if a corticosteroid injection to treat SIRVA is completed prior to this.⁹

Our patient’s outcome

We talked to the patient about treatment options, which included physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs), but the patient elected to go forward with a corticosteroid injection. We administered 2 cc of Depo-Medrol 40 mg/mL with 2 cc of 1% lidocaine without epinephrine and 2 cc of 0.5% ropivacaine into her right shoulder subacromial space using a posterior approach. The patient noticed a 70% improvement in her pain immediately following the injection.

Continue to: Considering her influenza vaccine...

Considering her influenza vaccine was administered more than 14 days prior to her corticosteroid injection, we felt that she had mounted enough of an immune response for the vaccination to have been adequate for protection.⁹ Therefore, we told her that she didn’t need to be revaccinated for influenza this season. The case was reported to the Vaccine Adverse Event Reporting System (VAERS).

In previous cases of vaccine-associated rotator cuff tendonopathy, T2 MRI images have shown focal inflammatory signal within the supraspinatous tendon and subacromial bursa.

At the patient’s 2-month follow up, she reported an overall 80% improvement in pain. She continued to have occasional discomfort with certain movements, although the pain was relieved with over-the-counter anti-inflammatory medication. On physical exam she had an intact arc of abduction of the right shoulder to 150° without pain. Forward flexion and external and internal rotation were normal and pain free. She had mild pain with resisted abduction and a positive Hawkin’s test. The patient agreed to go to physical therapy to work on rotator cuff strengthening. She denied any known influenza infection up to that time.

THE TAKEAWAY

It’s important to consider rotator cuff injuries or SIRVA as a potential adverse effect of influenza vaccination administration. Thin patients and those with low deltoid muscle mass are at risk of vaccine over-penetration, and proximally placed deltoid vaccines may reach the rotator cuff structures below. Staff should be trained on appropriate techniques for administering influenza vaccinations to avoid causing SIRVA. Specifically:

• Intramuscular vaccines injected into the deltoid muscle should be 3 fingerbreadths distal to the acromion. A more proximal approach could potentially contact the rotator cuff muscles.
• Vaccine administration should mirror the position of the patient (eg, if the patient is sitting, the administrator should be sitting; if the patient is standing, the administrator should be standing).
• Needle length for vaccine administration should be adjusted according to the patient’s weight (TABLE⁷).

Following vaccination, it is important to keep 2 other points in mind. First, if a subacromial corticosteroid injection is used for treatment of SIRVA within the first 2 weeks of vaccine administration, consider revaccination. Second, be sure to use the VAERS to report any clinically significant medical event that occurs after vaccination. VAERS is a national vaccine safety surveillance program that is supported by the CDC and the US Food and Drug Administration. The VAERS reporting system can be accessed through www.vaers.hhhs.gov.

CORRESPONDENCE
Dusty Marie Narducci, MD, 5290 Big Island Drive, Unit 1303, Jacksonville, FL 32246; dustymarienarducci@gmail.com

ILLUSTRATIVE CASE

A 46-year-old man with no significant past medical history presents to the emergency department (ED) with right flank pain and nausea. A computed tomography scan reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning on starting him on intravenous (IV) ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective nonsteroidal anti-inflammatory drug (NSAID). As a non-opiate analgesic, it is often the optimal first choice for the treatment of acute conditions such as flank, abdominal, musculoskeletal, and headache pains.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries a US Food and Drug Administration black box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose,” a dose at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the analgesic ceiling dose of ketorolac as 10 mg across dosage forms.^4,5 Yet, the majority of research and the majority of health care providers in current practice use higher doses of 20 to 60 mg. The US Food and Drug Administration label provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose of 10 mg in atleast 97% of patients who received IV doses and in at least 96% of patients receiving intramuscular (IM) doses in a US emergency department.⁶ If ketorolac 10 mg is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

Though often used at higher doses, 10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of 3 different doses of IV ketorolac for acute pain in 240 adult patients, ages 18 to 65 years, presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset ≤30 days.

Patients were randomized to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, and the syringes were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0 to 10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine 0.1 mg/kg was offered. The primary outcome was numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication.

The groups were similar in terms of demographics and baseline vital signs. The mean age of the participants was 39 to 42 years. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores were similar...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, but there was no difference between the groups; for the 10- and 15-mg groups, the mean pain scores post-intervention were 5.1 (95% confidence interval [CI] 4.5-5.7 and 4.5-5.6, respectively); and for the 30-mg group, the mean pain score was 4.8 (95% CI, 4.2-5.5). No P values were provided. There was no difference between the groups at any other time intervals. There was also no difference in the number of patients who needed rescue medication (morphine) at 30 minutes between the groups (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group; no P values were provided). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose (10 mg) of IV ketorolac is just as effective for acute pain control as higher 15- and 30-mg doses.

CAVEATS

A 2-hour time limit and no look at long-term effects

The ketorolac dose of 10 mg IV was specially prepared by the study pharmacist; it is unlikely this will be readily available in clinical settings. However, the 15-mg IV dose is also as effective as the higher 30-mg dose based on study results and is readily available.

A 10-mg dose of IV ketorolac is just as effective for acute pain control as a 15- or 30-mg IV dose.

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects like bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

A 10-mg single-dose vial is not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared. However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 46-year-old man with no significant past medical history presents to the emergency department (ED) with right flank pain and nausea. A computed tomography scan reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning on starting him on intravenous (IV) ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective nonsteroidal anti-inflammatory drug (NSAID). As a non-opiate analgesic, it is often the optimal first choice for the treatment of acute conditions such as flank, abdominal, musculoskeletal, and headache pains.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries a US Food and Drug Administration black box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose,” a dose at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the analgesic ceiling dose of ketorolac as 10 mg across dosage forms.^4,5 Yet, the majority of research and the majority of health care providers in current practice use higher doses of 20 to 60 mg. The US Food and Drug Administration label provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose of 10 mg in atleast 97% of patients who received IV doses and in at least 96% of patients receiving intramuscular (IM) doses in a US emergency department.⁶ If ketorolac 10 mg is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

Though often used at higher doses, 10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of 3 different doses of IV ketorolac for acute pain in 240 adult patients, ages 18 to 65 years, presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset ≤30 days.

Patients were randomized to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, and the syringes were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0 to 10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine 0.1 mg/kg was offered. The primary outcome was numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication.

The groups were similar in terms of demographics and baseline vital signs. The mean age of the participants was 39 to 42 years. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores were similar...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, but there was no difference between the groups; for the 10- and 15-mg groups, the mean pain scores post-intervention were 5.1 (95% confidence interval [CI] 4.5-5.7 and 4.5-5.6, respectively); and for the 30-mg group, the mean pain score was 4.8 (95% CI, 4.2-5.5). No P values were provided. There was no difference between the groups at any other time intervals. There was also no difference in the number of patients who needed rescue medication (morphine) at 30 minutes between the groups (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group; no P values were provided). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose (10 mg) of IV ketorolac is just as effective for acute pain control as higher 15- and 30-mg doses.

CAVEATS

A 2-hour time limit and no look at long-term effects

The ketorolac dose of 10 mg IV was specially prepared by the study pharmacist; it is unlikely this will be readily available in clinical settings. However, the 15-mg IV dose is also as effective as the higher 30-mg dose based on study results and is readily available.

A 10-mg dose of IV ketorolac is just as effective for acute pain control as a 15- or 30-mg IV dose.

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects like bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

A 10-mg single-dose vial is not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared. However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 46-year-old man with no significant past medical history presents to the emergency department (ED) with right flank pain and nausea. A computed tomography scan reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning on starting him on intravenous (IV) ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective nonsteroidal anti-inflammatory drug (NSAID). As a non-opiate analgesic, it is often the optimal first choice for the treatment of acute conditions such as flank, abdominal, musculoskeletal, and headache pains.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries a US Food and Drug Administration black box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose,” a dose at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the analgesic ceiling dose of ketorolac as 10 mg across dosage forms.^4,5 Yet, the majority of research and the majority of health care providers in current practice use higher doses of 20 to 60 mg. The US Food and Drug Administration label provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose of 10 mg in atleast 97% of patients who received IV doses and in at least 96% of patients receiving intramuscular (IM) doses in a US emergency department.⁶ If ketorolac 10 mg is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

Though often used at higher doses, 10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of 3 different doses of IV ketorolac for acute pain in 240 adult patients, ages 18 to 65 years, presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset ≤30 days.

Patients were randomized to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, and the syringes were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0 to 10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine 0.1 mg/kg was offered. The primary outcome was numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication.

The groups were similar in terms of demographics and baseline vital signs. The mean age of the participants was 39 to 42 years. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores were similar...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, but there was no difference between the groups; for the 10- and 15-mg groups, the mean pain scores post-intervention were 5.1 (95% confidence interval [CI] 4.5-5.7 and 4.5-5.6, respectively); and for the 30-mg group, the mean pain score was 4.8 (95% CI, 4.2-5.5). No P values were provided. There was no difference between the groups at any other time intervals. There was also no difference in the number of patients who needed rescue medication (morphine) at 30 minutes between the groups (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group; no P values were provided). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose (10 mg) of IV ketorolac is just as effective for acute pain control as higher 15- and 30-mg doses.

CAVEATS

A 2-hour time limit and no look at long-term effects

The ketorolac dose of 10 mg IV was specially prepared by the study pharmacist; it is unlikely this will be readily available in clinical settings. However, the 15-mg IV dose is also as effective as the higher 30-mg dose based on study results and is readily available.

A 10-mg dose of IV ketorolac is just as effective for acute pain control as a 15- or 30-mg IV dose.

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects like bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

A 10-mg single-dose vial is not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared. However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

THE CASE

Ms. E, a 42-year-old woman, visited her new physician for a physical exam. When asked about alcohol intake, she reported that she drank 3 to 4 beers after work and sometimes 5 to 8 beers a day on the weekends. Occasionally, she exceeded those amounts, but she didn’t feel guilty about her drinking. She was often late to work and said her relationship with her boyfriend was strained. A review of systems was positive for fatigue, poor concentration, abdominal pain, and weight gain. Her body mass index was 41, pulse 100 beats/min, blood pressure 125/75 mm Hg, and she was afebrile. Her physical exam was otherwise within normal limits.

How would you proceed with this patient?

Alcohol use disorder (AUD) is a common and often untreated condition that is increasingly prevalent in the United States.¹ The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) characterizes AUD as a combination of signs and symptoms typifying alcohol abuse and dependence (discussed in a bit).²

Data from the 2015 National Survey on Drug Use and Health (NSDUH) showed 15.7 million Americans with AUD, affecting 6.2% of the population ages 18 years or older and 2.5% of adolescents ages 12 to 17 years.³

Alcohol use and AUD account for an estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life years.⁴ AUD adversely affects several systems (TABLE 1⁵), and patients with AUD are sicker and more likely to die younger than those without AUD.⁴ In the United States, prevalence of AUD has increased in recent years among women, older adults, racial minorities, and individuals with a low education level.⁶

Screening for AUD is reasonable and straightforward, although diagnosis and treatment of AUD in primary care settings may be challenging due to competing clinical priorities; lack of training, resources, and support; and skepticism about the efficacy of behavioral and pharmacologic treatments.^7,8 However, family physicians are in an excellent position to diagnose and help address the complex biopsychosocial needs of patients with AUD, often in collaboration with colleagues and community organizations.

Signs and symptoms of AUD

In clinical practice, at least 2 of the following 11 behaviors or symptoms are required to diagnose AUD²:

• consuming larger amounts of alcohol over a longer period than intended
• persistent desire or unsuccessful efforts to cut down or control alcohol use
• making a significant effort to obtain, use, or recover from alcohol

In moderate-to-severe cases:

• cravings or urges to use alcohol
• recurrent failure to fulfill major work, school, or social obligations
• continued alcohol use despite recurrent social and interpersonal problems
• giving up social, occupational, and recreational activities due to alcohol
• using alcohol in physically dangerous situations
• continued alcohol use despite having physical or psychological problems
• tolerance to alcohol’s effects
• withdrawal symptoms.

Continue to: Patients meet criteria for mild AUD severity if...

Patients meet criteria for mild AUD severity if they exhibit 2 or 3 symptoms, moderate AUD with 4 or 5 symptoms, and severe AUD if there are 6 or more symptoms.²

USPSTF recommends screening for alcohol use disorder with the 10-question AUDIT, 3-question AUDIT-C, or single-question NIAAA tool.

Those who meet criteria for AUD and are able to stop using alcohol are deemed to be in early remission if the criteria have gone unfulfilled for at least 3 months and less than 12 months. Patients are considered to be in sustained remission if they have not met criteria for AUD at any time during a period of 12 months or longer.

How to detect AUD

Several clues in a patient’s history can suggest AUD (TABLE 2^9,10). Most imbibers are unaware of the dangers and may consider themselves merely “social drinkers.” Binge drinking may be an early indicator of vulnerability to AUD and should be assessed as part of a thorough clinical evaluation.¹¹ The US Preventive Services Task Force (USPSTF) recommends (Grade B) that clinicians screen adults ages 18 years or older for alcohol misuse.¹²

Studies demonstrate that both genetic and environmental factors play important roles in the development of AUD.¹³ A family history of excessive alcohol use increases the risk of AUD. Comorbidity of AUD and other mental health conditions is extremely common. For example, high rates of association between major depressive disorder and AUD have been observed.¹⁴

Tools to use in screening and diagnosing AUD

Screening for AUD during an office visit can be done fairly quickly. While 96% of primary care physicians screen for alcohol misuse in some way, only 38% use 1 of the 3 tools recommended by the USPSTF¹⁵—the Alcohol Use Disorders Identification Test (AUDIT), the abbreviated AUDIT-C, or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single question screen—which detect the full spectrum of alcohol misuse in adults.¹² Although the commonly used CAGE questionnaire is one of the most studied self-report tools, it has lower sensitivity at a lower level of alcohol intake.¹⁶

Continue to: The NIAAA single-question screen asks...

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.¹⁵ The sensitivity and specificity of single-question screening are 82% to 87% and 61% to 79%, respectively, and the test has been validated in several different settings.¹² The AUDIT screening tool, freely available from the World Health Organization, is a 10-item questionnaire that probes an individual’s alcohol intake, alcohol dependence, and adverse consequences of alcohol use. Administration of the AUDIT typically requires only 2 minutes. AUDIT-C¹⁷ is an abbreviated version of the AUDIT questionnaire that asks 3 consumption questions to screen for AUD.

It was found that AUDIT scores in the range of 8 to 15 indicate a medium-level alcohol problem, whereas a score of ≥16 indicates a high-level alcohol problem. The AUDIT-C is scored from 0 to 12, with ≥4 indicating a problem in men and ≥3 a problem in women.

THE CASE

The physician had used the NIAAA single- question screen to determine that Ms. E drank more than 4 beers per day during social events and weekends, which occurred 2 to 3 times per month over the past year. She lives alone and said that she’d been seeing less and less of her boyfriend lately. Her score on the Patient Health Questionnaire (PHQ), which screens for depression, was 11, indicating moderate impairment. Her response on the CAGE questionnaire was negative for a problem with alcohol. However, her AUDIT score was 17, indicating a high-level alcohol problem. Based on these findings, her physician expressed concern that her alcohol use might be contributing to her symptoms and difficulties.

The CAGE questionnaire has lower sensitivity when alcohol intake is lower.

Although she did not have a history of increasing usage per day, a persistent desire to cut down, significant effort to obtain alcohol, or cravings, she was having work troubles and continued to drink even though it was straining relationships, promoting weight gain, and causing abdominal pain.

The physician asked her to schedule a return visit and ordered several blood studies. He also offered to connect her with a colleague with whom he collaborated who could speak with her about possible alcohol use disorders and depression.

Continue to: Selecting blood work in screening for AUD

Lab tests used to measure hepatic injury due to alcohol include gamma-glutamyl-transferase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and macrocytic volume, although the indices of hepatic damage have low specificity. Elevated serum ethanol levels can reveal recent alcohol use, and vitamin deficiencies and other abnormalities can be used to differentiate other causes of hepatic inflammation and co-existing health issues (TABLE 3^10,18). A number of as-yet-unvalidated biomarkers are being studied to assist in screening, diagnosing, and treating AUD.¹⁸

What treatment approaches work for AUD?

Family physicians can efficiently and productively address AUD by using alcohol screening and brief intervention, which have been shown to reduce risky drinking. Reimbursement for this service is covered by such CPT codes as 99408, 99409, or H0049, or with other evaluation and management (E/M) codes by using modifier 25.

Treatment of AUD varies and should be customized to each patient’s needs, readiness, preferences, and resources. Individual and group counseling approaches can be effective, and medications are available for inpatient and outpatient settings. Psychotherapy options include brief interventions, 12-step programs (eg, Alcoholics Anonymous—https://www.aa.org/pages/en_US/find-aa-resources),motivational enhancement therapy, and cognitive behavioral therapy. Although it is beyond the scope of this article to describe these options in detail, resources are available for those who wish to learn more.^19-21

Psychopharmacologic management includes US Food and Drug Administration (FDA)-approved medications such as disulfiram, naltrexone, and acamprosate, and off-label uses of other medications (TABLE 4⁹). Not enough empiric evidence is available to judge the effectiveness of these medications in adolescents, and the FDA has not approved them for such use. Evidence from meta-analyses comparing naltrexone and acamprosate have shown naltrexone to be more efficacious in reducing heavy drinking and cravings, while acamprosate is effective in promoting abstinence.^22,23 Naltrexone combined with behavioral intervention reduces the heavy drinking days and percentage of abstinence days.²⁴

Current guideline recommendations from the American Psychiatric Association²⁵ include:

• Naltrexone and acamprosate are recommended to treat patients with moderate-to-severe AUD in specific circumstances (eg, when nonpharmacologic approaches have failed to produce an effect or when patients prefer to use one of these medications).
• Topiramate and gabapentin are also suggested as medications for patients with moderate-to-severe AUD, but typically after first trying naltrexone and acamprosate.
• Disulfiram generally should not be used as first-line treatment. It produces physical reactions (eg, flushing) if alcohol is consumed within 12 to 24 hours of medication use.

Continue to: THE CASE

Ms. E was open to the idea of decreasing her alcohol use and agreed that she was depressed. Her lab tests at follow-up were normal other than an elevated AST/ALT of 90/80 U/L. She received brief counseling from her family physician combined with cognitive behavioral therapy by a psychologist colleague. A subsequent ultrasound of her liver showed mild hepatomegaly and moderate-to-severe steatosis with nodularity of the liver, raising the possibility of cirrhosis.

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.

She continued to get counseling for her AUD and for her comorbid depression in addition to taking a selective serotonin reuptake inhibitor. She is now in early remission for her alcohol use.

CORRESPONDENCE
Jaividhya Dasarathy, MD, Department of Family Medicine, Metro Health Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109; jdasarathy@metrohealth.org.

THE CASE

Ms. E, a 42-year-old woman, visited her new physician for a physical exam. When asked about alcohol intake, she reported that she drank 3 to 4 beers after work and sometimes 5 to 8 beers a day on the weekends. Occasionally, she exceeded those amounts, but she didn’t feel guilty about her drinking. She was often late to work and said her relationship with her boyfriend was strained. A review of systems was positive for fatigue, poor concentration, abdominal pain, and weight gain. Her body mass index was 41, pulse 100 beats/min, blood pressure 125/75 mm Hg, and she was afebrile. Her physical exam was otherwise within normal limits.

How would you proceed with this patient?

Alcohol use disorder (AUD) is a common and often untreated condition that is increasingly prevalent in the United States.¹ The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) characterizes AUD as a combination of signs and symptoms typifying alcohol abuse and dependence (discussed in a bit).²

Data from the 2015 National Survey on Drug Use and Health (NSDUH) showed 15.7 million Americans with AUD, affecting 6.2% of the population ages 18 years or older and 2.5% of adolescents ages 12 to 17 years.³

Alcohol use and AUD account for an estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life years.⁴ AUD adversely affects several systems (TABLE 1⁵), and patients with AUD are sicker and more likely to die younger than those without AUD.⁴ In the United States, prevalence of AUD has increased in recent years among women, older adults, racial minorities, and individuals with a low education level.⁶

Screening for AUD is reasonable and straightforward, although diagnosis and treatment of AUD in primary care settings may be challenging due to competing clinical priorities; lack of training, resources, and support; and skepticism about the efficacy of behavioral and pharmacologic treatments.^7,8 However, family physicians are in an excellent position to diagnose and help address the complex biopsychosocial needs of patients with AUD, often in collaboration with colleagues and community organizations.

Signs and symptoms of AUD

In clinical practice, at least 2 of the following 11 behaviors or symptoms are required to diagnose AUD²:

• consuming larger amounts of alcohol over a longer period than intended
• persistent desire or unsuccessful efforts to cut down or control alcohol use
• making a significant effort to obtain, use, or recover from alcohol

In moderate-to-severe cases:

• cravings or urges to use alcohol
• recurrent failure to fulfill major work, school, or social obligations
• continued alcohol use despite recurrent social and interpersonal problems
• giving up social, occupational, and recreational activities due to alcohol
• using alcohol in physically dangerous situations
• continued alcohol use despite having physical or psychological problems
• tolerance to alcohol’s effects
• withdrawal symptoms.

Continue to: Patients meet criteria for mild AUD severity if...

Patients meet criteria for mild AUD severity if they exhibit 2 or 3 symptoms, moderate AUD with 4 or 5 symptoms, and severe AUD if there are 6 or more symptoms.²

USPSTF recommends screening for alcohol use disorder with the 10-question AUDIT, 3-question AUDIT-C, or single-question NIAAA tool.

Those who meet criteria for AUD and are able to stop using alcohol are deemed to be in early remission if the criteria have gone unfulfilled for at least 3 months and less than 12 months. Patients are considered to be in sustained remission if they have not met criteria for AUD at any time during a period of 12 months or longer.

How to detect AUD

Several clues in a patient’s history can suggest AUD (TABLE 2^9,10). Most imbibers are unaware of the dangers and may consider themselves merely “social drinkers.” Binge drinking may be an early indicator of vulnerability to AUD and should be assessed as part of a thorough clinical evaluation.¹¹ The US Preventive Services Task Force (USPSTF) recommends (Grade B) that clinicians screen adults ages 18 years or older for alcohol misuse.¹²

Studies demonstrate that both genetic and environmental factors play important roles in the development of AUD.¹³ A family history of excessive alcohol use increases the risk of AUD. Comorbidity of AUD and other mental health conditions is extremely common. For example, high rates of association between major depressive disorder and AUD have been observed.¹⁴

Tools to use in screening and diagnosing AUD

Screening for AUD during an office visit can be done fairly quickly. While 96% of primary care physicians screen for alcohol misuse in some way, only 38% use 1 of the 3 tools recommended by the USPSTF¹⁵—the Alcohol Use Disorders Identification Test (AUDIT), the abbreviated AUDIT-C, or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single question screen—which detect the full spectrum of alcohol misuse in adults.¹² Although the commonly used CAGE questionnaire is one of the most studied self-report tools, it has lower sensitivity at a lower level of alcohol intake.¹⁶

Continue to: The NIAAA single-question screen asks...

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.¹⁵ The sensitivity and specificity of single-question screening are 82% to 87% and 61% to 79%, respectively, and the test has been validated in several different settings.¹² The AUDIT screening tool, freely available from the World Health Organization, is a 10-item questionnaire that probes an individual’s alcohol intake, alcohol dependence, and adverse consequences of alcohol use. Administration of the AUDIT typically requires only 2 minutes. AUDIT-C¹⁷ is an abbreviated version of the AUDIT questionnaire that asks 3 consumption questions to screen for AUD.

It was found that AUDIT scores in the range of 8 to 15 indicate a medium-level alcohol problem, whereas a score of ≥16 indicates a high-level alcohol problem. The AUDIT-C is scored from 0 to 12, with ≥4 indicating a problem in men and ≥3 a problem in women.

THE CASE

The physician had used the NIAAA single- question screen to determine that Ms. E drank more than 4 beers per day during social events and weekends, which occurred 2 to 3 times per month over the past year. She lives alone and said that she’d been seeing less and less of her boyfriend lately. Her score on the Patient Health Questionnaire (PHQ), which screens for depression, was 11, indicating moderate impairment. Her response on the CAGE questionnaire was negative for a problem with alcohol. However, her AUDIT score was 17, indicating a high-level alcohol problem. Based on these findings, her physician expressed concern that her alcohol use might be contributing to her symptoms and difficulties.

The CAGE questionnaire has lower sensitivity when alcohol intake is lower.

Although she did not have a history of increasing usage per day, a persistent desire to cut down, significant effort to obtain alcohol, or cravings, she was having work troubles and continued to drink even though it was straining relationships, promoting weight gain, and causing abdominal pain.

The physician asked her to schedule a return visit and ordered several blood studies. He also offered to connect her with a colleague with whom he collaborated who could speak with her about possible alcohol use disorders and depression.

Continue to: Selecting blood work in screening for AUD

Lab tests used to measure hepatic injury due to alcohol include gamma-glutamyl-transferase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and macrocytic volume, although the indices of hepatic damage have low specificity. Elevated serum ethanol levels can reveal recent alcohol use, and vitamin deficiencies and other abnormalities can be used to differentiate other causes of hepatic inflammation and co-existing health issues (TABLE 3^10,18). A number of as-yet-unvalidated biomarkers are being studied to assist in screening, diagnosing, and treating AUD.¹⁸

What treatment approaches work for AUD?

Family physicians can efficiently and productively address AUD by using alcohol screening and brief intervention, which have been shown to reduce risky drinking. Reimbursement for this service is covered by such CPT codes as 99408, 99409, or H0049, or with other evaluation and management (E/M) codes by using modifier 25.

Treatment of AUD varies and should be customized to each patient’s needs, readiness, preferences, and resources. Individual and group counseling approaches can be effective, and medications are available for inpatient and outpatient settings. Psychotherapy options include brief interventions, 12-step programs (eg, Alcoholics Anonymous—https://www.aa.org/pages/en_US/find-aa-resources),motivational enhancement therapy, and cognitive behavioral therapy. Although it is beyond the scope of this article to describe these options in detail, resources are available for those who wish to learn more.^19-21

Psychopharmacologic management includes US Food and Drug Administration (FDA)-approved medications such as disulfiram, naltrexone, and acamprosate, and off-label uses of other medications (TABLE 4⁹). Not enough empiric evidence is available to judge the effectiveness of these medications in adolescents, and the FDA has not approved them for such use. Evidence from meta-analyses comparing naltrexone and acamprosate have shown naltrexone to be more efficacious in reducing heavy drinking and cravings, while acamprosate is effective in promoting abstinence.^22,23 Naltrexone combined with behavioral intervention reduces the heavy drinking days and percentage of abstinence days.²⁴

Current guideline recommendations from the American Psychiatric Association²⁵ include:

• Naltrexone and acamprosate are recommended to treat patients with moderate-to-severe AUD in specific circumstances (eg, when nonpharmacologic approaches have failed to produce an effect or when patients prefer to use one of these medications).
• Topiramate and gabapentin are also suggested as medications for patients with moderate-to-severe AUD, but typically after first trying naltrexone and acamprosate.
• Disulfiram generally should not be used as first-line treatment. It produces physical reactions (eg, flushing) if alcohol is consumed within 12 to 24 hours of medication use.

Continue to: THE CASE

Ms. E was open to the idea of decreasing her alcohol use and agreed that she was depressed. Her lab tests at follow-up were normal other than an elevated AST/ALT of 90/80 U/L. She received brief counseling from her family physician combined with cognitive behavioral therapy by a psychologist colleague. A subsequent ultrasound of her liver showed mild hepatomegaly and moderate-to-severe steatosis with nodularity of the liver, raising the possibility of cirrhosis.

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.

She continued to get counseling for her AUD and for her comorbid depression in addition to taking a selective serotonin reuptake inhibitor. She is now in early remission for her alcohol use.

CORRESPONDENCE
Jaividhya Dasarathy, MD, Department of Family Medicine, Metro Health Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109; jdasarathy@metrohealth.org.

THE CASE

Ms. E, a 42-year-old woman, visited her new physician for a physical exam. When asked about alcohol intake, she reported that she drank 3 to 4 beers after work and sometimes 5 to 8 beers a day on the weekends. Occasionally, she exceeded those amounts, but she didn’t feel guilty about her drinking. She was often late to work and said her relationship with her boyfriend was strained. A review of systems was positive for fatigue, poor concentration, abdominal pain, and weight gain. Her body mass index was 41, pulse 100 beats/min, blood pressure 125/75 mm Hg, and she was afebrile. Her physical exam was otherwise within normal limits.

How would you proceed with this patient?

Alcohol use disorder (AUD) is a common and often untreated condition that is increasingly prevalent in the United States.¹ The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) characterizes AUD as a combination of signs and symptoms typifying alcohol abuse and dependence (discussed in a bit).²

Data from the 2015 National Survey on Drug Use and Health (NSDUH) showed 15.7 million Americans with AUD, affecting 6.2% of the population ages 18 years or older and 2.5% of adolescents ages 12 to 17 years.³

Alcohol use and AUD account for an estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life years.⁴ AUD adversely affects several systems (TABLE 1⁵), and patients with AUD are sicker and more likely to die younger than those without AUD.⁴ In the United States, prevalence of AUD has increased in recent years among women, older adults, racial minorities, and individuals with a low education level.⁶

Screening for AUD is reasonable and straightforward, although diagnosis and treatment of AUD in primary care settings may be challenging due to competing clinical priorities; lack of training, resources, and support; and skepticism about the efficacy of behavioral and pharmacologic treatments.^7,8 However, family physicians are in an excellent position to diagnose and help address the complex biopsychosocial needs of patients with AUD, often in collaboration with colleagues and community organizations.

Signs and symptoms of AUD

In clinical practice, at least 2 of the following 11 behaviors or symptoms are required to diagnose AUD²:

• consuming larger amounts of alcohol over a longer period than intended
• persistent desire or unsuccessful efforts to cut down or control alcohol use
• making a significant effort to obtain, use, or recover from alcohol

In moderate-to-severe cases:

• cravings or urges to use alcohol
• recurrent failure to fulfill major work, school, or social obligations
• continued alcohol use despite recurrent social and interpersonal problems
• giving up social, occupational, and recreational activities due to alcohol
• using alcohol in physically dangerous situations
• continued alcohol use despite having physical or psychological problems
• tolerance to alcohol’s effects
• withdrawal symptoms.

Continue to: Patients meet criteria for mild AUD severity if...

Patients meet criteria for mild AUD severity if they exhibit 2 or 3 symptoms, moderate AUD with 4 or 5 symptoms, and severe AUD if there are 6 or more symptoms.²

USPSTF recommends screening for alcohol use disorder with the 10-question AUDIT, 3-question AUDIT-C, or single-question NIAAA tool.

Those who meet criteria for AUD and are able to stop using alcohol are deemed to be in early remission if the criteria have gone unfulfilled for at least 3 months and less than 12 months. Patients are considered to be in sustained remission if they have not met criteria for AUD at any time during a period of 12 months or longer.

How to detect AUD

Several clues in a patient’s history can suggest AUD (TABLE 2^9,10). Most imbibers are unaware of the dangers and may consider themselves merely “social drinkers.” Binge drinking may be an early indicator of vulnerability to AUD and should be assessed as part of a thorough clinical evaluation.¹¹ The US Preventive Services Task Force (USPSTF) recommends (Grade B) that clinicians screen adults ages 18 years or older for alcohol misuse.¹²

Studies demonstrate that both genetic and environmental factors play important roles in the development of AUD.¹³ A family history of excessive alcohol use increases the risk of AUD. Comorbidity of AUD and other mental health conditions is extremely common. For example, high rates of association between major depressive disorder and AUD have been observed.¹⁴

Tools to use in screening and diagnosing AUD

Screening for AUD during an office visit can be done fairly quickly. While 96% of primary care physicians screen for alcohol misuse in some way, only 38% use 1 of the 3 tools recommended by the USPSTF¹⁵—the Alcohol Use Disorders Identification Test (AUDIT), the abbreviated AUDIT-C, or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single question screen—which detect the full spectrum of alcohol misuse in adults.¹² Although the commonly used CAGE questionnaire is one of the most studied self-report tools, it has lower sensitivity at a lower level of alcohol intake.¹⁶

Continue to: The NIAAA single-question screen asks...

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.¹⁵ The sensitivity and specificity of single-question screening are 82% to 87% and 61% to 79%, respectively, and the test has been validated in several different settings.¹² The AUDIT screening tool, freely available from the World Health Organization, is a 10-item questionnaire that probes an individual’s alcohol intake, alcohol dependence, and adverse consequences of alcohol use. Administration of the AUDIT typically requires only 2 minutes. AUDIT-C¹⁷ is an abbreviated version of the AUDIT questionnaire that asks 3 consumption questions to screen for AUD.

It was found that AUDIT scores in the range of 8 to 15 indicate a medium-level alcohol problem, whereas a score of ≥16 indicates a high-level alcohol problem. The AUDIT-C is scored from 0 to 12, with ≥4 indicating a problem in men and ≥3 a problem in women.

THE CASE

The physician had used the NIAAA single- question screen to determine that Ms. E drank more than 4 beers per day during social events and weekends, which occurred 2 to 3 times per month over the past year. She lives alone and said that she’d been seeing less and less of her boyfriend lately. Her score on the Patient Health Questionnaire (PHQ), which screens for depression, was 11, indicating moderate impairment. Her response on the CAGE questionnaire was negative for a problem with alcohol. However, her AUDIT score was 17, indicating a high-level alcohol problem. Based on these findings, her physician expressed concern that her alcohol use might be contributing to her symptoms and difficulties.

The CAGE questionnaire has lower sensitivity when alcohol intake is lower.

Although she did not have a history of increasing usage per day, a persistent desire to cut down, significant effort to obtain alcohol, or cravings, she was having work troubles and continued to drink even though it was straining relationships, promoting weight gain, and causing abdominal pain.

The physician asked her to schedule a return visit and ordered several blood studies. He also offered to connect her with a colleague with whom he collaborated who could speak with her about possible alcohol use disorders and depression.

Continue to: Selecting blood work in screening for AUD

Lab tests used to measure hepatic injury due to alcohol include gamma-glutamyl-transferase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and macrocytic volume, although the indices of hepatic damage have low specificity. Elevated serum ethanol levels can reveal recent alcohol use, and vitamin deficiencies and other abnormalities can be used to differentiate other causes of hepatic inflammation and co-existing health issues (TABLE 3^10,18). A number of as-yet-unvalidated biomarkers are being studied to assist in screening, diagnosing, and treating AUD.¹⁸

What treatment approaches work for AUD?

Family physicians can efficiently and productively address AUD by using alcohol screening and brief intervention, which have been shown to reduce risky drinking. Reimbursement for this service is covered by such CPT codes as 99408, 99409, or H0049, or with other evaluation and management (E/M) codes by using modifier 25.

Treatment of AUD varies and should be customized to each patient’s needs, readiness, preferences, and resources. Individual and group counseling approaches can be effective, and medications are available for inpatient and outpatient settings. Psychotherapy options include brief interventions, 12-step programs (eg, Alcoholics Anonymous—https://www.aa.org/pages/en_US/find-aa-resources),motivational enhancement therapy, and cognitive behavioral therapy. Although it is beyond the scope of this article to describe these options in detail, resources are available for those who wish to learn more.^19-21

Psychopharmacologic management includes US Food and Drug Administration (FDA)-approved medications such as disulfiram, naltrexone, and acamprosate, and off-label uses of other medications (TABLE 4⁹). Not enough empiric evidence is available to judge the effectiveness of these medications in adolescents, and the FDA has not approved them for such use. Evidence from meta-analyses comparing naltrexone and acamprosate have shown naltrexone to be more efficacious in reducing heavy drinking and cravings, while acamprosate is effective in promoting abstinence.^22,23 Naltrexone combined with behavioral intervention reduces the heavy drinking days and percentage of abstinence days.²⁴

Current guideline recommendations from the American Psychiatric Association²⁵ include:

• Naltrexone and acamprosate are recommended to treat patients with moderate-to-severe AUD in specific circumstances (eg, when nonpharmacologic approaches have failed to produce an effect or when patients prefer to use one of these medications).
• Topiramate and gabapentin are also suggested as medications for patients with moderate-to-severe AUD, but typically after first trying naltrexone and acamprosate.
• Disulfiram generally should not be used as first-line treatment. It produces physical reactions (eg, flushing) if alcohol is consumed within 12 to 24 hours of medication use.

Continue to: THE CASE

Ms. E was open to the idea of decreasing her alcohol use and agreed that she was depressed. Her lab tests at follow-up were normal other than an elevated AST/ALT of 90/80 U/L. She received brief counseling from her family physician combined with cognitive behavioral therapy by a psychologist colleague. A subsequent ultrasound of her liver showed mild hepatomegaly and moderate-to-severe steatosis with nodularity of the liver, raising the possibility of cirrhosis.

The NIAAA single-question screen asks how many times in the past year the patient had ≥4 drinks (women) or ≥5 drinks (men) in a day.

She continued to get counseling for her AUD and for her comorbid depression in addition to taking a selective serotonin reuptake inhibitor. She is now in early remission for her alcohol use.

CORRESPONDENCE
Jaividhya Dasarathy, MD, Department of Family Medicine, Metro Health Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109; jdasarathy@metrohealth.org.

National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 revealed that 29% of adults in the United States have hypertension.¹ Prevalence increases with age, so that 7% of adults ages 18 to 39 years, 32% of adults ages 40 to 59, and 65% of adults ages ≥60 years have the disease.¹ This national survey data also showed that 53% of those given the diagnosis had uncontrolled hypertension, and that control of hypertension did not change significantly from 2009 to 2014.¹

Elevated blood pressure (BP) has been the leading risk factor for death related to cardiovascular disease globally for the last 3 decades.² Yet in 2 nationally representative samples, only 1 in 6 patients with documented BP ≥140/90 mm Hg received treatment intensification with new medication during primary care visits.³ Uncertainty about the representativeness of any single clinic BP measurement is a prominent reason for health care providers not to intensify therapy.⁴

Confirming the Dx outside the office. The 2015 US Preventive Services Task Force (USPSTF) guidelines on screening for hypertension state that, for most patients, a diagnosis of hypertension should be confirmed with out-of-office BP monitoring before initiating treatment.⁵ The USPSTF states that ambulatory BP monitoring (ABPM) is accurate for hypertension diagnosis and monitoring, and that home BP monitoring (HBPM) is an acceptable alternative, based on good quality evidence.

Access to ABPM, however, is often limited. In a 2015 survey of primary care clinics, only 25% of the 123 clinics that completed the questionnaire reported having access to it.⁶ Conversely, HBPM is widely available and acceptable to most patients. A recent NHANES survey showed that 43.5% of patients who were aware of their hypertension diagnosis engaged in HBPM.⁷

So what, exactly, should the role of HBPM be in the management of patients with hypertension? The evidence-based answers to the 10 questions that follow provide useful insights.

[polldaddy:10224678]

1. Can HBPM be used to confirm a Dx of hypertension?

Yes (Strength of recommendation [SOR] C).

In reviewing the diagnostic accuracy of various methods to confirm the diagnosis of hypertension, the USPSTF identified ABPM as the most accurate, followed by HBPM, with clinic BP measurements bringing up the rear.⁵ In adults ≥18 years of age, the USPSTF recommends obtaining BP measurements outside of the clinical setting for diagnostic confirmation before starting treatment unless the patient’s BP is ≥180/110 mm Hg, there is evidence of end-organ damage, or the patient has a diagnosis of secondary hypertension.⁵ The USPSTF recommends HBPM as an acceptable alternative to ABPM based on 6 studies including a total of 1253 participants.⁸ The percentage of patients with elevated office BP confirmed by HBPM to have hypertension was 45% to 84% across these 6 studies.

Sixteen studies from another systematic review evaluated the diagnostic accuracy of HBPM while using ABPM as a reference.⁹ This review found that HBPM had high specificity and negative predictive value, but low sensitivity and positive predictive value. There was moderate diagnostic agreement between HBPM and ABPM, with kappa statistic values of 0.37 to 0.73 across all studies.⁹

Continue to: In yet another study...

In yet another study, home BP and ambulatory BP measurements were identical when the same dual-mode device was used to measure both ambulatory and home BP.¹⁰

2. What are the diagnostic and treatment targets for home BP monitoring?

Treat patients if home BP is ≥130/80 mm Hg and categorize patients as normotensive if home BP is <125/76 mm Hg (SOR C). Monitor patients who are in between.

A 2017 joint statement from the American College of Cardiology/American Heart Association (ACC/AHA) Task Force states that the target BP for HBPM should be <130/80 mm Hg.¹¹ The Joint National Commission (JNC) 8 issued BP goals of <140/90 mm Hg for adults <60 years of age and those with diabetes and/or chronic kidney disease, and a goal of <150/90 mm Hg for adults ≥60 years of age with no diabetes or chronic kidney disease,¹² but much debate has recently surrounded these guidelines. JNC 8 does not provide a separate BP goal for HBPM.

Although based solely on evidence (and not patient-oriented outcomes), a home BP threshold of ≥135/85 mm Hg for the diagnosis and treatment of hypertension has been supported by the European Society of Hypertension consensus guidelines,¹³ results of a longitudinal study,¹⁴ meta-analyses of published studies, and a meta-analysis using individual subject data.¹⁵

Support for a home BP measurement of <125/76 mm Hg as normal is limited to a single cross-sectional study of 48 patients with 2 elevated office BP readings where the threshold of 125/76 mm Hg on home BP was shown to exclude 80% of patients diagnosed with hypertension by ambulatory readings.¹⁶ If home BP measurements are >125/76 mm Hgbut <135/85 mm Hg, 24-hour ambulatory BP monitoring is recommended to assess hypertension control.¹⁷

3. Does home BP monitoring improve hypertension control?

Yes, in the short term, but not in the long term (SOR C).

A meta-analysis of 13 comparative studies looking at HBPM alone vs usual care showed a small, but statistically significant, benefit of achieving target BP at 6 months with a relative risk ratio (RRR) of 1.3 (95% confidence interval [CI], 1.00-1.68; I²=77%).¹⁸ However, the pooled effects from 3 studies that measured the benefit of achieving a predefined BP target at the 12-month follow-up mark were not significant in this review (RRR=1.18; 95% CI, 0.95-1.46, I²=86%).¹⁸ The pooled effect from 19 studies from the same review showed that there was a statistically significant weighted mean difference of -3.9 mm Hg in systolic BP and a weighted mean difference of -2.4 mm Hg in diastolic BP at 6 months; however, the changes were no longer significant at the 12-month follow-up mark.¹⁸

Continue to: More than half of the studies included...

More than half of the studies included in the meta-analysis were of low quality, and none of the studies recruited patients based on differences in clinic BP and home BP patterns, but rather on controlled or uncontrolled hypertension status. The studies included in this meta-analysis measured final BP outcomes by measuring ambulatory BP or clinic BP.

Another systematic review of 19 studies and 7100 participants looking at how HBPM compared with ABPM as a measurement standard for BP control and patient outcomes found insufficient data to determine the benefit of using HBPM as a measurement standard for BP control.¹⁹

HBPM + added support. There was high-quality evidence from the meta-analysis that HBPM plus additional support vs usual care led to a reduction in BP and a higher proportion of patients achieving target BP.¹⁸ However, the additional support interventions in the studies were heterogeneous.

4. Should HBPM be used to detect a change in BP associated with medication alterations?

Yes (SOR B).

A 2008 meta-analysis²⁰ and several other studies^21,22 showed that HBPM has greater accuracy than office BP for identifying drug-induced BP changes. The 2008 meta-analysis looked at changes in office and home BP measurements produced by various antihypertensive drugs. In 7 studies that compared office BP measurements with home and ambulatory BP measurements, the 24-hour ambulatory BP measurements and home BP measurements showed less dramatic BP reductions with medications than clinic BP measurements.²⁰ This meta-analysis included 30 studies with 6794 participants and showed that home BP readings fell 20% less than office BP readings; the difference was statistically significant. These findings suggest that treatment-attributable changes in home BP and clinic BP measurements are linearly related, with the treatment effect on home BP measurements being around 80% of the effect on clinic BP measurements.

5. Do home BP measurements correlate with clinical outcomes?

Yes, and better than office BP measurements do; however, most studies comparing home BP measurements with usual care while looking at clinical outcomes are observational or quasi-experimental (SOR B).

For example, a 2015 systematic review looking at associations between BP measurement type (office, home, and ambulatory) and patient mortality found 5 observational studies that showed that adding home or ambulatory BP information improved cardiovascular risk prediction models. Moreover, all-cause mortality was associated with home BP and ambulatory BP levels only and not with office BP levels.¹⁹ The number of participants in these 5 studies varied between 210 and 2051 with study duration between 2.4 and 12.3 years. Of note, every study had a distinct population, affecting the generalizability of the results.

Continue to: One quasi-experimental study...

One quasi-experimental study with 450 participants showed that home BP measurements were at least as good as ambulatory BP measurements at predicting end organ damage related to hypertension when organ damage was measured by cardiac echocardiography, detection of microalbuminuria, and carotid echocardiography.²³ Similarly, a systematic review of 14 studies and 2485 participants comparing home, ambulatory, and office BP readings showed that home BP measurements’ association with left ventricular mass index is as good as that of ambulatory BP measurements, and superior to clinic BP readings.²⁴

6. Does HBPM help improve medication adherence?

The jury is still out on this one (SOR B).

Home blood pressure monitoring correlates better with clinical outcomes than does office blood pressure monitoring.

A 2006 systematic review of randomized controlled trials (RCTs) incorporating HBPM and evaluating medication adherence outcomes found that in 6 of the 11 studies identified, there was some improvement in medication adherence with HBPM.²⁵ However, only 1 of the 6 studies in this review involved HBPM as the sole intervention; the remaining 5 studies employed additional adherence-enhancing strategies.

Another systematic review looking at HBPM vs usual care included 8 studies (3 of moderate quality and 5 of low quality) that measured medication adherence (using varying measures of adherence) of which only 3 studies showed some improvement in medication adherence with HBPM.¹⁸

7. Does HBPM reduce therapeutic inertia?

Yes (SOR B).

A meta-analysis of 15 studies showed that therapeutic inertia was less common with HBPM than with office BP monitoring alone; the relative risk for unchanged medication was 0.82 (95% CI, 0.68 to 0.99) with HBPM.²⁶ However, 10 of the 15 studies were of low quality with a Jadad score ≤3.

8. Does HBPM, along with titration of treatment, improve BP outcomes?

Yes (SOR B).

Two RCTs that looked at self-monitoring of BP and self-titration of hypertensive medications showed significant reductions in BP levels.^27,28 In a cluster RCT of home BP telemonitoring, in which the pharmacist adjusted antihypertensives based on transmitted BP measurements, hypertension control was significantly better in the intervention group than in the usual care group (57.2% vs 30%).²⁹

Continue to: What are the recommended techniques for HBPM?

Patients should use a device that is validated, fully automated, and has an upper arm cuff (not a wrist monitor), according to a joint statement from the AHA, the American Society of Hypertension, and the Preventive Cardiovascular Nurses Association.¹⁷ (SOR C). (See validated BP monitor list at http://www.dableducational.org/sphygmomanometers/devices_2_sbpm.html.)

Patients should measure their BP in their nondominant arm after 5 minutes of rest with the arm at heart level, back supported, and feet flat on the ground. Patient technique and the accuracy of the home BP monitor should be checked annually. It is also recommended that patients check their BP 2 to 3 times every morning and evening. An average of 12 morning and evening measurements should be used for monitoring and treatment changes. An AHA informational sheet that shows how to measure BP properly can be found on their Web site (https://www.heart.org/-/media/files/health-topics/high-blood-pressure/how-to-measure-blood-pressure-letter-size-ucm_445846.pdf).

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.^30-33

10. What are the predictors of differences between home and office BP measurements?

Gender is one of the biggest predictors (SOR B).

A 2016 meta-analysis reported a total of 60 different hypothesized predictors of differences between home and clinic BP measurements (eg, gender, age, body mass index, systolic BP, diastolic BP). Masked hypertension was defined as a normal clinic BP reading and an elevated home BP reading. White coat hypertension was defined as an elevated clinic BP measurement with an acceptable home BP measurement. The researchers extracted odds ratios (ORs) for each study describing the association between patient characteristics and white coat or masked hypertension.³⁴ Studies of masked hypertension diagnosed from HBPM showed male gender as the most significant predictor of home-clinic BP differences (OR=1.47, 95% CI, 1.18-1.75). In contrast, female gender was the only significant predictor of white coat hypertension (OR=3.38; 95% CI, 1.64-6.96) when comparing home BP with clinic BP measurements.

Literature limitations and barriers to greater implementation

Most studies looking at HBPM outcomes have measured outcomes using ABPM or office BP measurements. The authors of studies using office BP as the outcome measure usually performed multiple BP measurements at often multiple office or clinic visits to calculate the true BP—a procedure that primary care practices rarely follow.³⁵ Additionally, there are significant methodologic differences in HBPM and ABPM; home BP is measured at rest, while ambulatory BP is measured while the patient is mobile and functioning. There are insufficient prospective studies looking at HBPM effects on clinical and patient-oriented outcomes.

The evidence clearly supports using HBPM in the diagnosis of hypertension and suggests its benefit in hypertension management. However, there are significant barriers to incorporating HBPM into practice—barriers that are largely unaddressed in the literature.

One of the biggest predictors of differences between home and office blood pressure measurements is gender.

For HBPM to be successful, patients need affordable validated home BP monitors covered by insurance that can translate home BP readings into usable information. Additional administrative and/or nursing assistance is required for patient education and support. Uploaded data need to be summarized in a way that is actionable and linked to the electronic health record.

Continue to: As the volume of patient-generated home date increases...

As the volume of patient-generated home data increases, there is a risk of information overload. Thus, meaningful summarization of the data is required to enable the physician, patient, and/or pharmacist to take prompt and effective action.

CORRESPONDENCE
Sonal J. Patil, MD, MSPH, Curtis W. and Ann H. Long Department of Family and Community Medicine, University of Missouri, MA306 Medical Sciences Building, DC032.00 Columbia, MO 65212; patilso@health.missouri.edu.

ACKNOWLEDGEMENTS
The authors are grateful to Dr. David R. Mehr for his valuable expertise in editing and proofreading this manuscript.

National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 revealed that 29% of adults in the United States have hypertension.¹ Prevalence increases with age, so that 7% of adults ages 18 to 39 years, 32% of adults ages 40 to 59, and 65% of adults ages ≥60 years have the disease.¹ This national survey data also showed that 53% of those given the diagnosis had uncontrolled hypertension, and that control of hypertension did not change significantly from 2009 to 2014.¹

Elevated blood pressure (BP) has been the leading risk factor for death related to cardiovascular disease globally for the last 3 decades.² Yet in 2 nationally representative samples, only 1 in 6 patients with documented BP ≥140/90 mm Hg received treatment intensification with new medication during primary care visits.³ Uncertainty about the representativeness of any single clinic BP measurement is a prominent reason for health care providers not to intensify therapy.⁴

Confirming the Dx outside the office. The 2015 US Preventive Services Task Force (USPSTF) guidelines on screening for hypertension state that, for most patients, a diagnosis of hypertension should be confirmed with out-of-office BP monitoring before initiating treatment.⁵ The USPSTF states that ambulatory BP monitoring (ABPM) is accurate for hypertension diagnosis and monitoring, and that home BP monitoring (HBPM) is an acceptable alternative, based on good quality evidence.

Access to ABPM, however, is often limited. In a 2015 survey of primary care clinics, only 25% of the 123 clinics that completed the questionnaire reported having access to it.⁶ Conversely, HBPM is widely available and acceptable to most patients. A recent NHANES survey showed that 43.5% of patients who were aware of their hypertension diagnosis engaged in HBPM.⁷

So what, exactly, should the role of HBPM be in the management of patients with hypertension? The evidence-based answers to the 10 questions that follow provide useful insights.

[polldaddy:10224678]

1. Can HBPM be used to confirm a Dx of hypertension?

Yes (Strength of recommendation [SOR] C).

In reviewing the diagnostic accuracy of various methods to confirm the diagnosis of hypertension, the USPSTF identified ABPM as the most accurate, followed by HBPM, with clinic BP measurements bringing up the rear.⁵ In adults ≥18 years of age, the USPSTF recommends obtaining BP measurements outside of the clinical setting for diagnostic confirmation before starting treatment unless the patient’s BP is ≥180/110 mm Hg, there is evidence of end-organ damage, or the patient has a diagnosis of secondary hypertension.⁵ The USPSTF recommends HBPM as an acceptable alternative to ABPM based on 6 studies including a total of 1253 participants.⁸ The percentage of patients with elevated office BP confirmed by HBPM to have hypertension was 45% to 84% across these 6 studies.

Sixteen studies from another systematic review evaluated the diagnostic accuracy of HBPM while using ABPM as a reference.⁹ This review found that HBPM had high specificity and negative predictive value, but low sensitivity and positive predictive value. There was moderate diagnostic agreement between HBPM and ABPM, with kappa statistic values of 0.37 to 0.73 across all studies.⁹

Continue to: In yet another study...

In yet another study, home BP and ambulatory BP measurements were identical when the same dual-mode device was used to measure both ambulatory and home BP.¹⁰

2. What are the diagnostic and treatment targets for home BP monitoring?

Treat patients if home BP is ≥130/80 mm Hg and categorize patients as normotensive if home BP is <125/76 mm Hg (SOR C). Monitor patients who are in between.

A 2017 joint statement from the American College of Cardiology/American Heart Association (ACC/AHA) Task Force states that the target BP for HBPM should be <130/80 mm Hg.¹¹ The Joint National Commission (JNC) 8 issued BP goals of <140/90 mm Hg for adults <60 years of age and those with diabetes and/or chronic kidney disease, and a goal of <150/90 mm Hg for adults ≥60 years of age with no diabetes or chronic kidney disease,¹² but much debate has recently surrounded these guidelines. JNC 8 does not provide a separate BP goal for HBPM.

Although based solely on evidence (and not patient-oriented outcomes), a home BP threshold of ≥135/85 mm Hg for the diagnosis and treatment of hypertension has been supported by the European Society of Hypertension consensus guidelines,¹³ results of a longitudinal study,¹⁴ meta-analyses of published studies, and a meta-analysis using individual subject data.¹⁵

Support for a home BP measurement of <125/76 mm Hg as normal is limited to a single cross-sectional study of 48 patients with 2 elevated office BP readings where the threshold of 125/76 mm Hg on home BP was shown to exclude 80% of patients diagnosed with hypertension by ambulatory readings.¹⁶ If home BP measurements are >125/76 mm Hgbut <135/85 mm Hg, 24-hour ambulatory BP monitoring is recommended to assess hypertension control.¹⁷

3. Does home BP monitoring improve hypertension control?

Yes, in the short term, but not in the long term (SOR C).

A meta-analysis of 13 comparative studies looking at HBPM alone vs usual care showed a small, but statistically significant, benefit of achieving target BP at 6 months with a relative risk ratio (RRR) of 1.3 (95% confidence interval [CI], 1.00-1.68; I²=77%).¹⁸ However, the pooled effects from 3 studies that measured the benefit of achieving a predefined BP target at the 12-month follow-up mark were not significant in this review (RRR=1.18; 95% CI, 0.95-1.46, I²=86%).¹⁸ The pooled effect from 19 studies from the same review showed that there was a statistically significant weighted mean difference of -3.9 mm Hg in systolic BP and a weighted mean difference of -2.4 mm Hg in diastolic BP at 6 months; however, the changes were no longer significant at the 12-month follow-up mark.¹⁸

Continue to: More than half of the studies included...

More than half of the studies included in the meta-analysis were of low quality, and none of the studies recruited patients based on differences in clinic BP and home BP patterns, but rather on controlled or uncontrolled hypertension status. The studies included in this meta-analysis measured final BP outcomes by measuring ambulatory BP or clinic BP.

Another systematic review of 19 studies and 7100 participants looking at how HBPM compared with ABPM as a measurement standard for BP control and patient outcomes found insufficient data to determine the benefit of using HBPM as a measurement standard for BP control.¹⁹

HBPM + added support. There was high-quality evidence from the meta-analysis that HBPM plus additional support vs usual care led to a reduction in BP and a higher proportion of patients achieving target BP.¹⁸ However, the additional support interventions in the studies were heterogeneous.

4. Should HBPM be used to detect a change in BP associated with medication alterations?

Yes (SOR B).

A 2008 meta-analysis²⁰ and several other studies^21,22 showed that HBPM has greater accuracy than office BP for identifying drug-induced BP changes. The 2008 meta-analysis looked at changes in office and home BP measurements produced by various antihypertensive drugs. In 7 studies that compared office BP measurements with home and ambulatory BP measurements, the 24-hour ambulatory BP measurements and home BP measurements showed less dramatic BP reductions with medications than clinic BP measurements.²⁰ This meta-analysis included 30 studies with 6794 participants and showed that home BP readings fell 20% less than office BP readings; the difference was statistically significant. These findings suggest that treatment-attributable changes in home BP and clinic BP measurements are linearly related, with the treatment effect on home BP measurements being around 80% of the effect on clinic BP measurements.

5. Do home BP measurements correlate with clinical outcomes?

Yes, and better than office BP measurements do; however, most studies comparing home BP measurements with usual care while looking at clinical outcomes are observational or quasi-experimental (SOR B).

For example, a 2015 systematic review looking at associations between BP measurement type (office, home, and ambulatory) and patient mortality found 5 observational studies that showed that adding home or ambulatory BP information improved cardiovascular risk prediction models. Moreover, all-cause mortality was associated with home BP and ambulatory BP levels only and not with office BP levels.¹⁹ The number of participants in these 5 studies varied between 210 and 2051 with study duration between 2.4 and 12.3 years. Of note, every study had a distinct population, affecting the generalizability of the results.

Continue to: One quasi-experimental study...

One quasi-experimental study with 450 participants showed that home BP measurements were at least as good as ambulatory BP measurements at predicting end organ damage related to hypertension when organ damage was measured by cardiac echocardiography, detection of microalbuminuria, and carotid echocardiography.²³ Similarly, a systematic review of 14 studies and 2485 participants comparing home, ambulatory, and office BP readings showed that home BP measurements’ association with left ventricular mass index is as good as that of ambulatory BP measurements, and superior to clinic BP readings.²⁴

6. Does HBPM help improve medication adherence?

The jury is still out on this one (SOR B).

Home blood pressure monitoring correlates better with clinical outcomes than does office blood pressure monitoring.

A 2006 systematic review of randomized controlled trials (RCTs) incorporating HBPM and evaluating medication adherence outcomes found that in 6 of the 11 studies identified, there was some improvement in medication adherence with HBPM.²⁵ However, only 1 of the 6 studies in this review involved HBPM as the sole intervention; the remaining 5 studies employed additional adherence-enhancing strategies.

Another systematic review looking at HBPM vs usual care included 8 studies (3 of moderate quality and 5 of low quality) that measured medication adherence (using varying measures of adherence) of which only 3 studies showed some improvement in medication adherence with HBPM.¹⁸

7. Does HBPM reduce therapeutic inertia?

Yes (SOR B).

A meta-analysis of 15 studies showed that therapeutic inertia was less common with HBPM than with office BP monitoring alone; the relative risk for unchanged medication was 0.82 (95% CI, 0.68 to 0.99) with HBPM.²⁶ However, 10 of the 15 studies were of low quality with a Jadad score ≤3.

8. Does HBPM, along with titration of treatment, improve BP outcomes?

Yes (SOR B).

Two RCTs that looked at self-monitoring of BP and self-titration of hypertensive medications showed significant reductions in BP levels.^27,28 In a cluster RCT of home BP telemonitoring, in which the pharmacist adjusted antihypertensives based on transmitted BP measurements, hypertension control was significantly better in the intervention group than in the usual care group (57.2% vs 30%).²⁹

Continue to: What are the recommended techniques for HBPM?

Patients should use a device that is validated, fully automated, and has an upper arm cuff (not a wrist monitor), according to a joint statement from the AHA, the American Society of Hypertension, and the Preventive Cardiovascular Nurses Association.¹⁷ (SOR C). (See validated BP monitor list at http://www.dableducational.org/sphygmomanometers/devices_2_sbpm.html.)

Patients should measure their BP in their nondominant arm after 5 minutes of rest with the arm at heart level, back supported, and feet flat on the ground. Patient technique and the accuracy of the home BP monitor should be checked annually. It is also recommended that patients check their BP 2 to 3 times every morning and evening. An average of 12 morning and evening measurements should be used for monitoring and treatment changes. An AHA informational sheet that shows how to measure BP properly can be found on their Web site (https://www.heart.org/-/media/files/health-topics/high-blood-pressure/how-to-measure-blood-pressure-letter-size-ucm_445846.pdf).

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.^30-33

10. What are the predictors of differences between home and office BP measurements?

Gender is one of the biggest predictors (SOR B).

A 2016 meta-analysis reported a total of 60 different hypothesized predictors of differences between home and clinic BP measurements (eg, gender, age, body mass index, systolic BP, diastolic BP). Masked hypertension was defined as a normal clinic BP reading and an elevated home BP reading. White coat hypertension was defined as an elevated clinic BP measurement with an acceptable home BP measurement. The researchers extracted odds ratios (ORs) for each study describing the association between patient characteristics and white coat or masked hypertension.³⁴ Studies of masked hypertension diagnosed from HBPM showed male gender as the most significant predictor of home-clinic BP differences (OR=1.47, 95% CI, 1.18-1.75). In contrast, female gender was the only significant predictor of white coat hypertension (OR=3.38; 95% CI, 1.64-6.96) when comparing home BP with clinic BP measurements.

Literature limitations and barriers to greater implementation

Most studies looking at HBPM outcomes have measured outcomes using ABPM or office BP measurements. The authors of studies using office BP as the outcome measure usually performed multiple BP measurements at often multiple office or clinic visits to calculate the true BP—a procedure that primary care practices rarely follow.³⁵ Additionally, there are significant methodologic differences in HBPM and ABPM; home BP is measured at rest, while ambulatory BP is measured while the patient is mobile and functioning. There are insufficient prospective studies looking at HBPM effects on clinical and patient-oriented outcomes.

The evidence clearly supports using HBPM in the diagnosis of hypertension and suggests its benefit in hypertension management. However, there are significant barriers to incorporating HBPM into practice—barriers that are largely unaddressed in the literature.

One of the biggest predictors of differences between home and office blood pressure measurements is gender.

For HBPM to be successful, patients need affordable validated home BP monitors covered by insurance that can translate home BP readings into usable information. Additional administrative and/or nursing assistance is required for patient education and support. Uploaded data need to be summarized in a way that is actionable and linked to the electronic health record.

Continue to: As the volume of patient-generated home date increases...

As the volume of patient-generated home data increases, there is a risk of information overload. Thus, meaningful summarization of the data is required to enable the physician, patient, and/or pharmacist to take prompt and effective action.

CORRESPONDENCE
Sonal J. Patil, MD, MSPH, Curtis W. and Ann H. Long Department of Family and Community Medicine, University of Missouri, MA306 Medical Sciences Building, DC032.00 Columbia, MO 65212; patilso@health.missouri.edu.

ACKNOWLEDGEMENTS
The authors are grateful to Dr. David R. Mehr for his valuable expertise in editing and proofreading this manuscript.

National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 revealed that 29% of adults in the United States have hypertension.¹ Prevalence increases with age, so that 7% of adults ages 18 to 39 years, 32% of adults ages 40 to 59, and 65% of adults ages ≥60 years have the disease.¹ This national survey data also showed that 53% of those given the diagnosis had uncontrolled hypertension, and that control of hypertension did not change significantly from 2009 to 2014.¹

Elevated blood pressure (BP) has been the leading risk factor for death related to cardiovascular disease globally for the last 3 decades.² Yet in 2 nationally representative samples, only 1 in 6 patients with documented BP ≥140/90 mm Hg received treatment intensification with new medication during primary care visits.³ Uncertainty about the representativeness of any single clinic BP measurement is a prominent reason for health care providers not to intensify therapy.⁴

Confirming the Dx outside the office. The 2015 US Preventive Services Task Force (USPSTF) guidelines on screening for hypertension state that, for most patients, a diagnosis of hypertension should be confirmed with out-of-office BP monitoring before initiating treatment.⁵ The USPSTF states that ambulatory BP monitoring (ABPM) is accurate for hypertension diagnosis and monitoring, and that home BP monitoring (HBPM) is an acceptable alternative, based on good quality evidence.

Access to ABPM, however, is often limited. In a 2015 survey of primary care clinics, only 25% of the 123 clinics that completed the questionnaire reported having access to it.⁶ Conversely, HBPM is widely available and acceptable to most patients. A recent NHANES survey showed that 43.5% of patients who were aware of their hypertension diagnosis engaged in HBPM.⁷

So what, exactly, should the role of HBPM be in the management of patients with hypertension? The evidence-based answers to the 10 questions that follow provide useful insights.

[polldaddy:10224678]

1. Can HBPM be used to confirm a Dx of hypertension?

Yes (Strength of recommendation [SOR] C).

In reviewing the diagnostic accuracy of various methods to confirm the diagnosis of hypertension, the USPSTF identified ABPM as the most accurate, followed by HBPM, with clinic BP measurements bringing up the rear.⁵ In adults ≥18 years of age, the USPSTF recommends obtaining BP measurements outside of the clinical setting for diagnostic confirmation before starting treatment unless the patient’s BP is ≥180/110 mm Hg, there is evidence of end-organ damage, or the patient has a diagnosis of secondary hypertension.⁵ The USPSTF recommends HBPM as an acceptable alternative to ABPM based on 6 studies including a total of 1253 participants.⁸ The percentage of patients with elevated office BP confirmed by HBPM to have hypertension was 45% to 84% across these 6 studies.

Sixteen studies from another systematic review evaluated the diagnostic accuracy of HBPM while using ABPM as a reference.⁹ This review found that HBPM had high specificity and negative predictive value, but low sensitivity and positive predictive value. There was moderate diagnostic agreement between HBPM and ABPM, with kappa statistic values of 0.37 to 0.73 across all studies.⁹

Continue to: In yet another study...

In yet another study, home BP and ambulatory BP measurements were identical when the same dual-mode device was used to measure both ambulatory and home BP.¹⁰

2. What are the diagnostic and treatment targets for home BP monitoring?

Treat patients if home BP is ≥130/80 mm Hg and categorize patients as normotensive if home BP is <125/76 mm Hg (SOR C). Monitor patients who are in between.

A 2017 joint statement from the American College of Cardiology/American Heart Association (ACC/AHA) Task Force states that the target BP for HBPM should be <130/80 mm Hg.¹¹ The Joint National Commission (JNC) 8 issued BP goals of <140/90 mm Hg for adults <60 years of age and those with diabetes and/or chronic kidney disease, and a goal of <150/90 mm Hg for adults ≥60 years of age with no diabetes or chronic kidney disease,¹² but much debate has recently surrounded these guidelines. JNC 8 does not provide a separate BP goal for HBPM.

Although based solely on evidence (and not patient-oriented outcomes), a home BP threshold of ≥135/85 mm Hg for the diagnosis and treatment of hypertension has been supported by the European Society of Hypertension consensus guidelines,¹³ results of a longitudinal study,¹⁴ meta-analyses of published studies, and a meta-analysis using individual subject data.¹⁵

Support for a home BP measurement of <125/76 mm Hg as normal is limited to a single cross-sectional study of 48 patients with 2 elevated office BP readings where the threshold of 125/76 mm Hg on home BP was shown to exclude 80% of patients diagnosed with hypertension by ambulatory readings.¹⁶ If home BP measurements are >125/76 mm Hgbut <135/85 mm Hg, 24-hour ambulatory BP monitoring is recommended to assess hypertension control.¹⁷

3. Does home BP monitoring improve hypertension control?

Yes, in the short term, but not in the long term (SOR C).

A meta-analysis of 13 comparative studies looking at HBPM alone vs usual care showed a small, but statistically significant, benefit of achieving target BP at 6 months with a relative risk ratio (RRR) of 1.3 (95% confidence interval [CI], 1.00-1.68; I²=77%).¹⁸ However, the pooled effects from 3 studies that measured the benefit of achieving a predefined BP target at the 12-month follow-up mark were not significant in this review (RRR=1.18; 95% CI, 0.95-1.46, I²=86%).¹⁸ The pooled effect from 19 studies from the same review showed that there was a statistically significant weighted mean difference of -3.9 mm Hg in systolic BP and a weighted mean difference of -2.4 mm Hg in diastolic BP at 6 months; however, the changes were no longer significant at the 12-month follow-up mark.¹⁸

Continue to: More than half of the studies included...

More than half of the studies included in the meta-analysis were of low quality, and none of the studies recruited patients based on differences in clinic BP and home BP patterns, but rather on controlled or uncontrolled hypertension status. The studies included in this meta-analysis measured final BP outcomes by measuring ambulatory BP or clinic BP.

Another systematic review of 19 studies and 7100 participants looking at how HBPM compared with ABPM as a measurement standard for BP control and patient outcomes found insufficient data to determine the benefit of using HBPM as a measurement standard for BP control.¹⁹

HBPM + added support. There was high-quality evidence from the meta-analysis that HBPM plus additional support vs usual care led to a reduction in BP and a higher proportion of patients achieving target BP.¹⁸ However, the additional support interventions in the studies were heterogeneous.

4. Should HBPM be used to detect a change in BP associated with medication alterations?

Yes (SOR B).

A 2008 meta-analysis²⁰ and several other studies^21,22 showed that HBPM has greater accuracy than office BP for identifying drug-induced BP changes. The 2008 meta-analysis looked at changes in office and home BP measurements produced by various antihypertensive drugs. In 7 studies that compared office BP measurements with home and ambulatory BP measurements, the 24-hour ambulatory BP measurements and home BP measurements showed less dramatic BP reductions with medications than clinic BP measurements.²⁰ This meta-analysis included 30 studies with 6794 participants and showed that home BP readings fell 20% less than office BP readings; the difference was statistically significant. These findings suggest that treatment-attributable changes in home BP and clinic BP measurements are linearly related, with the treatment effect on home BP measurements being around 80% of the effect on clinic BP measurements.

5. Do home BP measurements correlate with clinical outcomes?

Yes, and better than office BP measurements do; however, most studies comparing home BP measurements with usual care while looking at clinical outcomes are observational or quasi-experimental (SOR B).

For example, a 2015 systematic review looking at associations between BP measurement type (office, home, and ambulatory) and patient mortality found 5 observational studies that showed that adding home or ambulatory BP information improved cardiovascular risk prediction models. Moreover, all-cause mortality was associated with home BP and ambulatory BP levels only and not with office BP levels.¹⁹ The number of participants in these 5 studies varied between 210 and 2051 with study duration between 2.4 and 12.3 years. Of note, every study had a distinct population, affecting the generalizability of the results.

Continue to: One quasi-experimental study...

One quasi-experimental study with 450 participants showed that home BP measurements were at least as good as ambulatory BP measurements at predicting end organ damage related to hypertension when organ damage was measured by cardiac echocardiography, detection of microalbuminuria, and carotid echocardiography.²³ Similarly, a systematic review of 14 studies and 2485 participants comparing home, ambulatory, and office BP readings showed that home BP measurements’ association with left ventricular mass index is as good as that of ambulatory BP measurements, and superior to clinic BP readings.²⁴

6. Does HBPM help improve medication adherence?

The jury is still out on this one (SOR B).

Home blood pressure monitoring correlates better with clinical outcomes than does office blood pressure monitoring.

A 2006 systematic review of randomized controlled trials (RCTs) incorporating HBPM and evaluating medication adherence outcomes found that in 6 of the 11 studies identified, there was some improvement in medication adherence with HBPM.²⁵ However, only 1 of the 6 studies in this review involved HBPM as the sole intervention; the remaining 5 studies employed additional adherence-enhancing strategies.

Another systematic review looking at HBPM vs usual care included 8 studies (3 of moderate quality and 5 of low quality) that measured medication adherence (using varying measures of adherence) of which only 3 studies showed some improvement in medication adherence with HBPM.¹⁸

7. Does HBPM reduce therapeutic inertia?

Yes (SOR B).

A meta-analysis of 15 studies showed that therapeutic inertia was less common with HBPM than with office BP monitoring alone; the relative risk for unchanged medication was 0.82 (95% CI, 0.68 to 0.99) with HBPM.²⁶ However, 10 of the 15 studies were of low quality with a Jadad score ≤3.

8. Does HBPM, along with titration of treatment, improve BP outcomes?

Yes (SOR B).

Two RCTs that looked at self-monitoring of BP and self-titration of hypertensive medications showed significant reductions in BP levels.^27,28 In a cluster RCT of home BP telemonitoring, in which the pharmacist adjusted antihypertensives based on transmitted BP measurements, hypertension control was significantly better in the intervention group than in the usual care group (57.2% vs 30%).²⁹

Continue to: What are the recommended techniques for HBPM?

Patients should use a device that is validated, fully automated, and has an upper arm cuff (not a wrist monitor), according to a joint statement from the AHA, the American Society of Hypertension, and the Preventive Cardiovascular Nurses Association.¹⁷ (SOR C). (See validated BP monitor list at http://www.dableducational.org/sphygmomanometers/devices_2_sbpm.html.)

Patients should measure their BP in their nondominant arm after 5 minutes of rest with the arm at heart level, back supported, and feet flat on the ground. Patient technique and the accuracy of the home BP monitor should be checked annually. It is also recommended that patients check their BP 2 to 3 times every morning and evening. An average of 12 morning and evening measurements should be used for monitoring and treatment changes. An AHA informational sheet that shows how to measure BP properly can be found on their Web site (https://www.heart.org/-/media/files/health-topics/high-blood-pressure/how-to-measure-blood-pressure-letter-size-ucm_445846.pdf).

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.

Several studies examining the accuracy of measuring BP over clothing did not find significant differences in BP measurements performed on a bare arm vs over a sleeve.^30-33

10. What are the predictors of differences between home and office BP measurements?

Gender is one of the biggest predictors (SOR B).

A 2016 meta-analysis reported a total of 60 different hypothesized predictors of differences between home and clinic BP measurements (eg, gender, age, body mass index, systolic BP, diastolic BP). Masked hypertension was defined as a normal clinic BP reading and an elevated home BP reading. White coat hypertension was defined as an elevated clinic BP measurement with an acceptable home BP measurement. The researchers extracted odds ratios (ORs) for each study describing the association between patient characteristics and white coat or masked hypertension.³⁴ Studies of masked hypertension diagnosed from HBPM showed male gender as the most significant predictor of home-clinic BP differences (OR=1.47, 95% CI, 1.18-1.75). In contrast, female gender was the only significant predictor of white coat hypertension (OR=3.38; 95% CI, 1.64-6.96) when comparing home BP with clinic BP measurements.

Literature limitations and barriers to greater implementation

Most studies looking at HBPM outcomes have measured outcomes using ABPM or office BP measurements. The authors of studies using office BP as the outcome measure usually performed multiple BP measurements at often multiple office or clinic visits to calculate the true BP—a procedure that primary care practices rarely follow.³⁵ Additionally, there are significant methodologic differences in HBPM and ABPM; home BP is measured at rest, while ambulatory BP is measured while the patient is mobile and functioning. There are insufficient prospective studies looking at HBPM effects on clinical and patient-oriented outcomes.

The evidence clearly supports using HBPM in the diagnosis of hypertension and suggests its benefit in hypertension management. However, there are significant barriers to incorporating HBPM into practice—barriers that are largely unaddressed in the literature.

One of the biggest predictors of differences between home and office blood pressure measurements is gender.

For HBPM to be successful, patients need affordable validated home BP monitors covered by insurance that can translate home BP readings into usable information. Additional administrative and/or nursing assistance is required for patient education and support. Uploaded data need to be summarized in a way that is actionable and linked to the electronic health record.

Continue to: As the volume of patient-generated home date increases...

As the volume of patient-generated home data increases, there is a risk of information overload. Thus, meaningful summarization of the data is required to enable the physician, patient, and/or pharmacist to take prompt and effective action.

CORRESPONDENCE
Sonal J. Patil, MD, MSPH, Curtis W. and Ann H. Long Department of Family and Community Medicine, University of Missouri, MA306 Medical Sciences Building, DC032.00 Columbia, MO 65212; patilso@health.missouri.edu.

ACKNOWLEDGEMENTS
The authors are grateful to Dr. David R. Mehr for his valuable expertise in editing and proofreading this manuscript.