THE CASE

A 16-year-old hockey player presented to our emergency department with sharp pain in his right upper chest after “checking” another player during a game. The pain did not resolve with rest and was worse with movement and breathing. The patient did not have dysphagia, dyspnea, paresthesias, or hoarseness. The physical examination revealed tenderness over the right sternoclavicular joint (SCJ) without swelling or deformity. A distal neurovascular exam was intact, and a chest x-ray showed no evidence of dislocation or fracture (FIGURE 1A). The patient’s pain was refractory to multiple intravenous (IV) pain medications.

THE DIAGNOSIS

A computed tomography (CT) scan with IV contrast of the chest demonstrated posterior and superior dislocation of the right clavicular head. Despite the close proximity of the dislocated head to the brachiocephalic artery (FIGURE 1B-1D), there was no vascular injury.

DISCUSSION

Posterior sternoclavicular dislocations (PSCDs) can be difficult to diagnose. Edema can mask the characteristic skin depression that one would expect with a posterior dislocation.¹ Chest radiographs are often normal (as was true in this case). Patients may present with an abnormal pulse, paresthesias, hoarseness, dysphagia, and/or dyspnea. However, for more than half of these patients, their only signs and symptoms will be pain, swelling, and limited range of motion.¹ As a result, a PSCD may be misdiagnosed as a ligamentous or soft tissue injury.¹

 

 

An uncommon injury that can result in serious complications

PSCDs represent 3% to 5% of all SCJ dislocations, which comprise <5% of all shoulder girdle injuries.¹ Nevertheless, prompt and accurate diagnosis is critical, as these dislocations involve a high risk for injury to the posterior structures, particularly the brachiocephalic vein, right common carotid artery, and aortic arch.

One study found that nearly 75% of patients had a significant structure <1 cm posterior to the SCJ.² This proximity can result in neurovascular complications—some of which are devastating—in up to 30% of patients with PSCDs.³ A case report from 2011, for example, describes a 19-year-old man who had an undiagnosed PSCD that caused a pseudoaneurysm in his subclavian artery and a subsequent thrombotic cerebrovascular accident.⁴

Which injuries should raise your suspicions? Injuries in which lateral compression on the shoulder has caused it to roll forward and those in which a posteriorly directed force has been applied to the medial clavicle (as might occur in tackle sports or motor vehicle rollovers) should increase suspicion of a PSCD.¹

Proper diagnosis requires CT angiography of the chest to assess the injury and evaluate the underlying structures. If CT is not available, additional chest film views, such as a serendipity view (anteroposterior view with 40° cephalic tilt) or Heinig view (oblique projection perpendicular to SCJ), may be obtained; an ultrasound is also an option.⁵

PSCD = surgical emergency

Following diagnosis, immediate orthopedic consultation is required. A PSCD is a surgical emergency. Reduction (open or closed) must be performed under general anesthesia with vascular and/or cardiothoracic surgery specialists available, as the reduction itself could injure one of the great vessels. Fortunately, most patients do quite well following surgery, with the majority achieving good-to-excellent results.⁶

Our patient was admitted to the hospital and underwent orthopedic surgery the following morning. Vascular and cardiothoracic surgeons were consulted and available in the event of a complication. A Salter-Harris type 2 fracture of the medial clavicle was identified intraoperatively, and an open reduction with internal fixation was performed. The patient had an uneventful recovery and resumed his usual activities, including playing hockey.

THE TAKEAWAY

PSCDs, although uncommon, can be life-threatening. Since the physical exam is unreliable and standard radiographs are often normal, accurate diagnosis relies largely on increased clinical suspicion. When there is a history of shoulder trauma, medial clavicle pain, and SCJ edema or tenderness, a PSCD should be suspected.⁷

Confirm the diagnosis with CT angiogram, and remember that a PSCD is a surgical emergency that requires coordination with orthopedic and vascular/cardiothoracic surgeons.

THE CASE

A 16-year-old hockey player presented to our emergency department with sharp pain in his right upper chest after “checking” another player during a game. The pain did not resolve with rest and was worse with movement and breathing. The patient did not have dysphagia, dyspnea, paresthesias, or hoarseness. The physical examination revealed tenderness over the right sternoclavicular joint (SCJ) without swelling or deformity. A distal neurovascular exam was intact, and a chest x-ray showed no evidence of dislocation or fracture (FIGURE 1A). The patient’s pain was refractory to multiple intravenous (IV) pain medications.

THE DIAGNOSIS

A computed tomography (CT) scan with IV contrast of the chest demonstrated posterior and superior dislocation of the right clavicular head. Despite the close proximity of the dislocated head to the brachiocephalic artery (FIGURE 1B-1D), there was no vascular injury.

DISCUSSION

Posterior sternoclavicular dislocations (PSCDs) can be difficult to diagnose. Edema can mask the characteristic skin depression that one would expect with a posterior dislocation.¹ Chest radiographs are often normal (as was true in this case). Patients may present with an abnormal pulse, paresthesias, hoarseness, dysphagia, and/or dyspnea. However, for more than half of these patients, their only signs and symptoms will be pain, swelling, and limited range of motion.¹ As a result, a PSCD may be misdiagnosed as a ligamentous or soft tissue injury.¹

 

 

An uncommon injury that can result in serious complications

PSCDs represent 3% to 5% of all SCJ dislocations, which comprise <5% of all shoulder girdle injuries.¹ Nevertheless, prompt and accurate diagnosis is critical, as these dislocations involve a high risk for injury to the posterior structures, particularly the brachiocephalic vein, right common carotid artery, and aortic arch.

One study found that nearly 75% of patients had a significant structure <1 cm posterior to the SCJ.² This proximity can result in neurovascular complications—some of which are devastating—in up to 30% of patients with PSCDs.³ A case report from 2011, for example, describes a 19-year-old man who had an undiagnosed PSCD that caused a pseudoaneurysm in his subclavian artery and a subsequent thrombotic cerebrovascular accident.⁴

Which injuries should raise your suspicions? Injuries in which lateral compression on the shoulder has caused it to roll forward and those in which a posteriorly directed force has been applied to the medial clavicle (as might occur in tackle sports or motor vehicle rollovers) should increase suspicion of a PSCD.¹

Proper diagnosis requires CT angiography of the chest to assess the injury and evaluate the underlying structures. If CT is not available, additional chest film views, such as a serendipity view (anteroposterior view with 40° cephalic tilt) or Heinig view (oblique projection perpendicular to SCJ), may be obtained; an ultrasound is also an option.⁵

PSCD = surgical emergency

Following diagnosis, immediate orthopedic consultation is required. A PSCD is a surgical emergency. Reduction (open or closed) must be performed under general anesthesia with vascular and/or cardiothoracic surgery specialists available, as the reduction itself could injure one of the great vessels. Fortunately, most patients do quite well following surgery, with the majority achieving good-to-excellent results.⁶

Our patient was admitted to the hospital and underwent orthopedic surgery the following morning. Vascular and cardiothoracic surgeons were consulted and available in the event of a complication. A Salter-Harris type 2 fracture of the medial clavicle was identified intraoperatively, and an open reduction with internal fixation was performed. The patient had an uneventful recovery and resumed his usual activities, including playing hockey.

THE TAKEAWAY

PSCDs, although uncommon, can be life-threatening. Since the physical exam is unreliable and standard radiographs are often normal, accurate diagnosis relies largely on increased clinical suspicion. When there is a history of shoulder trauma, medial clavicle pain, and SCJ edema or tenderness, a PSCD should be suspected.⁷

Confirm the diagnosis with CT angiogram, and remember that a PSCD is a surgical emergency that requires coordination with orthopedic and vascular/cardiothoracic surgeons.

THE CASE

A 16-year-old hockey player presented to our emergency department with sharp pain in his right upper chest after “checking” another player during a game. The pain did not resolve with rest and was worse with movement and breathing. The patient did not have dysphagia, dyspnea, paresthesias, or hoarseness. The physical examination revealed tenderness over the right sternoclavicular joint (SCJ) without swelling or deformity. A distal neurovascular exam was intact, and a chest x-ray showed no evidence of dislocation or fracture (FIGURE 1A). The patient’s pain was refractory to multiple intravenous (IV) pain medications.

THE DIAGNOSIS

A computed tomography (CT) scan with IV contrast of the chest demonstrated posterior and superior dislocation of the right clavicular head. Despite the close proximity of the dislocated head to the brachiocephalic artery (FIGURE 1B-1D), there was no vascular injury.

DISCUSSION

Posterior sternoclavicular dislocations (PSCDs) can be difficult to diagnose. Edema can mask the characteristic skin depression that one would expect with a posterior dislocation.¹ Chest radiographs are often normal (as was true in this case). Patients may present with an abnormal pulse, paresthesias, hoarseness, dysphagia, and/or dyspnea. However, for more than half of these patients, their only signs and symptoms will be pain, swelling, and limited range of motion.¹ As a result, a PSCD may be misdiagnosed as a ligamentous or soft tissue injury.¹

 

 

An uncommon injury that can result in serious complications

PSCDs represent 3% to 5% of all SCJ dislocations, which comprise <5% of all shoulder girdle injuries.¹ Nevertheless, prompt and accurate diagnosis is critical, as these dislocations involve a high risk for injury to the posterior structures, particularly the brachiocephalic vein, right common carotid artery, and aortic arch.

One study found that nearly 75% of patients had a significant structure <1 cm posterior to the SCJ.² This proximity can result in neurovascular complications—some of which are devastating—in up to 30% of patients with PSCDs.³ A case report from 2011, for example, describes a 19-year-old man who had an undiagnosed PSCD that caused a pseudoaneurysm in his subclavian artery and a subsequent thrombotic cerebrovascular accident.⁴

Which injuries should raise your suspicions? Injuries in which lateral compression on the shoulder has caused it to roll forward and those in which a posteriorly directed force has been applied to the medial clavicle (as might occur in tackle sports or motor vehicle rollovers) should increase suspicion of a PSCD.¹

Proper diagnosis requires CT angiography of the chest to assess the injury and evaluate the underlying structures. If CT is not available, additional chest film views, such as a serendipity view (anteroposterior view with 40° cephalic tilt) or Heinig view (oblique projection perpendicular to SCJ), may be obtained; an ultrasound is also an option.⁵

PSCD = surgical emergency

Following diagnosis, immediate orthopedic consultation is required. A PSCD is a surgical emergency. Reduction (open or closed) must be performed under general anesthesia with vascular and/or cardiothoracic surgery specialists available, as the reduction itself could injure one of the great vessels. Fortunately, most patients do quite well following surgery, with the majority achieving good-to-excellent results.⁶

Our patient was admitted to the hospital and underwent orthopedic surgery the following morning. Vascular and cardiothoracic surgeons were consulted and available in the event of a complication. A Salter-Harris type 2 fracture of the medial clavicle was identified intraoperatively, and an open reduction with internal fixation was performed. The patient had an uneventful recovery and resumed his usual activities, including playing hockey.

THE TAKEAWAY

PSCDs, although uncommon, can be life-threatening. Since the physical exam is unreliable and standard radiographs are often normal, accurate diagnosis relies largely on increased clinical suspicion. When there is a history of shoulder trauma, medial clavicle pain, and SCJ edema or tenderness, a PSCD should be suspected.⁷

Confirm the diagnosis with CT angiogram, and remember that a PSCD is a surgical emergency that requires coordination with orthopedic and vascular/cardiothoracic surgeons.

An estimated 39.4 million US adults suffer from persistent pain,¹ and the National Institutes of Health indicate that pain affects more Americans than diabetes, heart disease, and cancer combined.²

As physicians, we know that conventional options to manage chronic pain leave much to be desired and that more evidence-based treatment options are sorely needed. Patients know this, too, and turn to complementary therapies for pain more than for any other diagnosis.³

Case in point: The use of acupuncture is growing. Its use in the United States tripled between 1997 and 2007.⁴ In addition, the research base for acupuncture is rapidly expanding. From 1991 to 2009, nearly 4000 acupuncture research studies were published, with studies on pain accounting for 41% of the acupuncture literature.⁴

But acupuncture is not without controversy. This is due to a lack of a universally accepted biologic mechanism, theories of use and efficacy based in an alternative medical system (traditional Chinese medicine [TCM]), and conflicting views of the evidence.

This article will help make sense of this growing body of knowledge by summarizing the latest evidence and addressing 7 common questions about acupuncture for pain conditions. Applying this information will give you the confidence to counsel patients appropriately and decide if acupuncture fits within their pain management plan.

1. What is acupuncture and how does it work?

Acupuncture, which has a 2000-year history of use, involves inserting needles at various points throughout the body to promote healing and improve function. Although acupuncture represents one piece of TCM (which is a holistic system that also includes herbal medicine, nutrition, meditation, and movement), it is often offered as an independent therapy.

Acupuncture point locations are determined either by using an underlying theoretical framework, such as TCM, or by using anatomic structures, such as muscular trigger points. Providers today often employ a hybrid approach when delivering acupuncture treatment. That is, practitioners may choose point locations based on TCM, but they may combine the practice with local treatments that are based on current knowledge of anatomy. For example, a patient presenting with low back pain may be treated utilizing traditional points located near the ankle and knee, and also by needling active trigger points in the quadratus lumborum muscle.

The mechanism of action. One of the reasons for the continuing controversy surrounding acupuncture is the lack of a clear understanding of its underlying mechanism of action. For centuries the “how” of acupuncture has been explained in poetic terms such as yin, yang, and qi. Only in the past half-century have we begun investigating the potential biologic mechanisms responsible for the physiologic effects seen with acupuncture treatment.

While research has uncovered several interesting theories, how these mechanisms interact to produce therapeutic effects is still unclear. However, looking at various components of the nervous system helps to provide some insight.

Consider the nervous system. One way to conceptualize the mechanisms of acupuncture is to consider the various levels of the nervous system and how each level is affected. In the central nervous system, needling an acupuncture point stimulates the natural endorphin system, altering the pain sensation.⁵ This effect is reversible with naloxone in animal models, indicating that blocking the endorphin system interferes with the analgesic benefits of acupuncture.⁵

Serotonergic systems are also involved centrally. Functional magnetic resonance imaging studies have shown that needling specific acupuncture points modulates areas of the brain.

In the spinal cord, the gate control theory is believed to play a role. (The gate control theory puts forth that nonpainful input closes the “gates” to painful input, which prevents pain sensations from traveling to the central nervous system.) Modulation of sensory input occurs at the level of the dorsal horn of the spinal cord during an acupuncture treatment, which can affect the physiologic pain response.⁶ Opioid receptors are also affected at the spinal cord level.⁷

Acupuncture use in the United States tripled between 1997 and 2007.

Lastly, multiple chemicals released peripherally, including interleukins, substance P, and adenosine, appear to contribute to acupuncture’s analgesia.⁶ We know this because a local anesthetic injected around a peripheral nerve at an acupoint blocks the analgesic effect of acupuncture.⁸ Taken together, acupuncture treatment produces physiologic changes in the brain, spinal cord, and at the periphery, making it a truly unique therapeutic modality.

2. Is acupuncture an effective treatment for pain?

Yes, but before we look at the individual studies, it is important to mention some of the shortcomings of the research to date. First, acupuncture trials lack a standard sham control intervention. Some sham treatments involve skin penetration, while others do not. This has led to controversy regarding whether the sham interventions themselves are physiologically active, thus lessening the magnitude of effect for acupuncture. This is a point of contention in the acupuncture literature and a factor to consider when deciding if results have clinical significance.

In addition, the acupuncturist providing treatment in a trial is typically unblinded. This is also true of trials measuring other physical modalities, but it contributes to the debate surrounding the magnitude of placebo response in acupuncture studies.

Finally, many randomized trials involving acupuncture have had low methodologic quality. Fortunately, there are now several high-quality systematic reviews that have attempted to filter out the lower-quality research and provide a better representation of the evidence (TABLE^9-14). A discussion of them follows.

General chronic pain. A 2012 meta-analysis¹⁵ evaluated the effectiveness of acupuncture for the treatment of chronic pain with one of 4 etiologies: nonspecific back or neck pain, chronic headache, osteoarthritis, and shoulder pain. This analysis attempted to control for the high variability of study quality in the acupuncture literature by including only studies of high methodologic character. The final analysis included 29 randomized controlled trials (N=17,922). The authors concluded that acupuncture was superior to both no acupuncture and sham (placebo) acupuncture for all pain conditions in the study. The average effect size was 0.5 standard deviations on a 10-point scale. The authors considered this to be clinically relevant, although the magnitude of benefit was modest.¹⁵

Low back pain. A 2017 systematic review by Chou et al⁹ evaluated 32 trials (N=5931) reviewing acupuncture for the treatment of chronic low back pain. This review found acupuncture was associated with lower pain intensity and improved function in the short term when compared with no treatment. And while acupuncture was associated with lower pain intensity when compared with a sham control, there was no difference in function between the 2 groups. Of note, 3 of the included trials compared acupuncture to standard medications used in the treatment of low back pain and found acupuncture to be superior in terms of both pain reduction and improved function.⁹

Trials that compared acupuncture to another active therapy have found that it often has fewer adverse effects.

The authors of a 2008 systematic review that evaluated 23 trials (N=6359)¹⁰ similarly concluded that there is moderate evidence for the use of acupuncture (compared to no treatment) for the treatment of nonspecific low back pain, but did not find evidence that acupuncture was superior to sham controls.¹⁰ The 2017 American College of Physicians clinical practice guidelines support the use of acupuncture for the treatment of chronic low back pain.¹⁶

In addition to helping with chronic low back pain, acupuncture is also showing promise as a treatment for acute spinal pain. A 2013 systematic review (11 trials, N=1139) showed that acupuncture may be more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) in treating acute low back pain and may cause fewer adverse effects.¹⁷

Headache pain. Evidence favoring acupuncture in the management of headache has been fairly consistent over the past decade. An updated Cochrane review on the prevention of migraine headaches was published in 2016.¹¹ Acupuncture was compared with no treatment in 4 trials (n=2199). The authors found moderate quality evidence that acupuncture reduces headache frequency (number needed to treat=4). Acupuncture achieved at least 50% headache reduction in 41% vs 17% in the groups that received no acupuncture. When compared with sham control groups (10 trials, n=1534), acupuncture demonstrated a small but statistically significant improvement in headache frequency. Three trials (n=744) compared acupuncture to medication prophylaxis for migraine headaches and found acupuncture had similar effectiveness with fewer adverse effects.¹¹

Osteoarthritis (OA). Most studies have focused on OA of the knee, and, thus far, have generated conflicting results. A Cochrane review in 2010 included 4 trials (n=884) that had a wait list control and 9 trials (n=1835) that compared acupuncture to a sham control.¹² When compared to a wait list control, acupuncture resulted in statistically significant and clinically relevant improvement in pain and function. However, when compared to sham treatment for OA, the review showed statistically significant improvement in pain and function for acupuncture that was unlikely to be clinically relevant.¹²

A more recent meta-analysis in 2016 evaluated 10 trials (N=2007) investigating acupuncture in the treatment of knee OA.¹³ The authors found acupuncture improved both pain and functional outcome measures when compared with either no treatment or a sham control.

Fibromyalgia. Systematic reviews in 2007 (5 trials, N=316)¹⁸ and 2010 (7 trials, N=385)¹⁹ showed that acupuncture did provide short-term pain relief in patients with fibromyalgia, but that the effect was not sustained at follow-up.These reviews were limited by a high risk of bias, which was noted in the studies. The authors of both reviews concluded that acupuncture could not be recommended for the treatment of fibromyalgia.

A more recent Cochrane review published in 2013 (9 trials, N=395) offered low- to moderate-level evidence of benefit for acupuncture compared with no treatment at one month follow-up.¹⁴ Of note, there was also evidence of benefit in improved sleep and global well-being, in addition to pain and stiffness measures in this review. The overall magnitude of benefit was small, but clinically significant. Acupuncture also has evidence of benefit in the treatment of conditions commonly seen in conjunction with fibromyalgia, including headaches and low back pain as described earlier.

3. What does a typical acupuncture treatment entail?

In a typical treatment, anywhere from about 5 to 20 needles are inserted into the body. Common areas of needling include the arms and legs, especially below the elbows and knees. Other frequently used areas are the scalp, ears, and structures related to the painful condition.

The needles used are very thin (typically smaller than a 30-gauge needle) and do not have a beveled tip like phlebotomy needles do. Most patients have minimal pain as the needles are inserted. During the treatment, the needles may be left alone or they may be heated or stimulated electrically. An average treatment lasts 30 to 40 minutes; many patients find the sessions relaxing.

4. Are there any adverse effects or complications of treatment?

Acupuncture is generally considered a safe therapy, with most patients experiencing no adverse effects at all. Minor adverse effects can include post-treatment fatigue, minor bruising, or vasovagal reactions from the insertion of the needles. Serious complications, such as pneumothorax, are possible, but are considered rare.²⁰ A 2004 study estimated the incidence of severe complications to be .05 per 10,000 acupuncture treatments.²¹

Infections are also possible, but most reported cases were due to practitioners reusing needles.²² The standard of care in the United States is to use only sterilized, single-use needles. With this practice, infections due to acupuncture are thought to be rare.

Of note, trials that compare acupuncture to another active therapy often find that acupuncture has fewer adverse effects. This has been the case when acupuncture was compared to NSAIDs for low back pain and to topiramate for headaches.^17,23

5. How does acupuncture fit into a patient’s treatment?

The simple answer is that it is often most effectively used as part of a comprehensive management plan for chronic pain.

As our understanding of the complexity of chronic pain deepens, our therapeutic armamentarium for the management of chronic pain needs to broaden. This was summed up well in a 2016 article on the multimodal management of chronic pain when the authors stated, “Many targets need more than one arrow.”²⁴ Effective management of chronic pain involves addressing psychosocial and lifestyle factors in a patient-centered way and finding a combination of treatments that most effectively leads to improved coping and function.

It’s important to note that like medications and injections, acupuncture is a passive therapy. Although there is evidence for efficacy of improved pain with acupuncture in certain conditions, it should be combined with treatments that actively engage patients, such as exercise, behavioral treatments, development of coping skills, sleep hygiene, and educational strategies.

6. To whom do I refer patients for acupuncture treatment?

In the United States, licensed acupuncturists and physicians most commonly perform acupuncture. There are more than 50 schools that train licensed acupuncturists in the United States, and it usually takes 3 years to meet the requirements.²⁵

Physicians are often trained through continuing medical education (CME) programs that take several months to complete. These programs often combine live lectures, distance learning, and hands-on training and are typically sponsored by a university. Most require 300 hours of CME to complete. Licensure varies by state, but in many states, having an MD or DO degree automatically allows physicians to practice acupuncture. (See “Online resources,” above for links to Web sites that can be useful in finding qualified acupuncturists in your area.)

7. Is acupuncture covered by insurance?

Patients can expect to pay $75 to $150 for an acupuncture session.

It depends. Insurance coverage of acupuncture is highly variable and based on region and insurance type. Medicare and Medicaid plans do not pay for acupuncture. There are some private insurance plans that do. If covered, there may be limitations regarding diagnosis, number of visits, or provider. It is best for patients to call their insurance plan directly to inquire about coverage and any limitations. If paying out of pocket, patients can expect to pay $75 to $150 per treatment session.

CORRESPONDENCE
Russell Lemmon, DO, 1100 Delaplaine Court, Madison, WI 53715; [email protected].

An estimated 39.4 million US adults suffer from persistent pain,¹ and the National Institutes of Health indicate that pain affects more Americans than diabetes, heart disease, and cancer combined.²

As physicians, we know that conventional options to manage chronic pain leave much to be desired and that more evidence-based treatment options are sorely needed. Patients know this, too, and turn to complementary therapies for pain more than for any other diagnosis.³

Case in point: The use of acupuncture is growing. Its use in the United States tripled between 1997 and 2007.⁴ In addition, the research base for acupuncture is rapidly expanding. From 1991 to 2009, nearly 4000 acupuncture research studies were published, with studies on pain accounting for 41% of the acupuncture literature.⁴

But acupuncture is not without controversy. This is due to a lack of a universally accepted biologic mechanism, theories of use and efficacy based in an alternative medical system (traditional Chinese medicine [TCM]), and conflicting views of the evidence.

This article will help make sense of this growing body of knowledge by summarizing the latest evidence and addressing 7 common questions about acupuncture for pain conditions. Applying this information will give you the confidence to counsel patients appropriately and decide if acupuncture fits within their pain management plan.

1. What is acupuncture and how does it work?

Acupuncture, which has a 2000-year history of use, involves inserting needles at various points throughout the body to promote healing and improve function. Although acupuncture represents one piece of TCM (which is a holistic system that also includes herbal medicine, nutrition, meditation, and movement), it is often offered as an independent therapy.

Acupuncture point locations are determined either by using an underlying theoretical framework, such as TCM, or by using anatomic structures, such as muscular trigger points. Providers today often employ a hybrid approach when delivering acupuncture treatment. That is, practitioners may choose point locations based on TCM, but they may combine the practice with local treatments that are based on current knowledge of anatomy. For example, a patient presenting with low back pain may be treated utilizing traditional points located near the ankle and knee, and also by needling active trigger points in the quadratus lumborum muscle.

The mechanism of action. One of the reasons for the continuing controversy surrounding acupuncture is the lack of a clear understanding of its underlying mechanism of action. For centuries the “how” of acupuncture has been explained in poetic terms such as yin, yang, and qi. Only in the past half-century have we begun investigating the potential biologic mechanisms responsible for the physiologic effects seen with acupuncture treatment.

While research has uncovered several interesting theories, how these mechanisms interact to produce therapeutic effects is still unclear. However, looking at various components of the nervous system helps to provide some insight.

Consider the nervous system. One way to conceptualize the mechanisms of acupuncture is to consider the various levels of the nervous system and how each level is affected. In the central nervous system, needling an acupuncture point stimulates the natural endorphin system, altering the pain sensation.⁵ This effect is reversible with naloxone in animal models, indicating that blocking the endorphin system interferes with the analgesic benefits of acupuncture.⁵

Serotonergic systems are also involved centrally. Functional magnetic resonance imaging studies have shown that needling specific acupuncture points modulates areas of the brain.

In the spinal cord, the gate control theory is believed to play a role. (The gate control theory puts forth that nonpainful input closes the “gates” to painful input, which prevents pain sensations from traveling to the central nervous system.) Modulation of sensory input occurs at the level of the dorsal horn of the spinal cord during an acupuncture treatment, which can affect the physiologic pain response.⁶ Opioid receptors are also affected at the spinal cord level.⁷

Acupuncture use in the United States tripled between 1997 and 2007.

Lastly, multiple chemicals released peripherally, including interleukins, substance P, and adenosine, appear to contribute to acupuncture’s analgesia.⁶ We know this because a local anesthetic injected around a peripheral nerve at an acupoint blocks the analgesic effect of acupuncture.⁸ Taken together, acupuncture treatment produces physiologic changes in the brain, spinal cord, and at the periphery, making it a truly unique therapeutic modality.

2. Is acupuncture an effective treatment for pain?

Yes, but before we look at the individual studies, it is important to mention some of the shortcomings of the research to date. First, acupuncture trials lack a standard sham control intervention. Some sham treatments involve skin penetration, while others do not. This has led to controversy regarding whether the sham interventions themselves are physiologically active, thus lessening the magnitude of effect for acupuncture. This is a point of contention in the acupuncture literature and a factor to consider when deciding if results have clinical significance.

In addition, the acupuncturist providing treatment in a trial is typically unblinded. This is also true of trials measuring other physical modalities, but it contributes to the debate surrounding the magnitude of placebo response in acupuncture studies.

Finally, many randomized trials involving acupuncture have had low methodologic quality. Fortunately, there are now several high-quality systematic reviews that have attempted to filter out the lower-quality research and provide a better representation of the evidence (TABLE^9-14). A discussion of them follows.

General chronic pain. A 2012 meta-analysis¹⁵ evaluated the effectiveness of acupuncture for the treatment of chronic pain with one of 4 etiologies: nonspecific back or neck pain, chronic headache, osteoarthritis, and shoulder pain. This analysis attempted to control for the high variability of study quality in the acupuncture literature by including only studies of high methodologic character. The final analysis included 29 randomized controlled trials (N=17,922). The authors concluded that acupuncture was superior to both no acupuncture and sham (placebo) acupuncture for all pain conditions in the study. The average effect size was 0.5 standard deviations on a 10-point scale. The authors considered this to be clinically relevant, although the magnitude of benefit was modest.¹⁵

Low back pain. A 2017 systematic review by Chou et al⁹ evaluated 32 trials (N=5931) reviewing acupuncture for the treatment of chronic low back pain. This review found acupuncture was associated with lower pain intensity and improved function in the short term when compared with no treatment. And while acupuncture was associated with lower pain intensity when compared with a sham control, there was no difference in function between the 2 groups. Of note, 3 of the included trials compared acupuncture to standard medications used in the treatment of low back pain and found acupuncture to be superior in terms of both pain reduction and improved function.⁹

Trials that compared acupuncture to another active therapy have found that it often has fewer adverse effects.

The authors of a 2008 systematic review that evaluated 23 trials (N=6359)¹⁰ similarly concluded that there is moderate evidence for the use of acupuncture (compared to no treatment) for the treatment of nonspecific low back pain, but did not find evidence that acupuncture was superior to sham controls.¹⁰ The 2017 American College of Physicians clinical practice guidelines support the use of acupuncture for the treatment of chronic low back pain.¹⁶

In addition to helping with chronic low back pain, acupuncture is also showing promise as a treatment for acute spinal pain. A 2013 systematic review (11 trials, N=1139) showed that acupuncture may be more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) in treating acute low back pain and may cause fewer adverse effects.¹⁷

Headache pain. Evidence favoring acupuncture in the management of headache has been fairly consistent over the past decade. An updated Cochrane review on the prevention of migraine headaches was published in 2016.¹¹ Acupuncture was compared with no treatment in 4 trials (n=2199). The authors found moderate quality evidence that acupuncture reduces headache frequency (number needed to treat=4). Acupuncture achieved at least 50% headache reduction in 41% vs 17% in the groups that received no acupuncture. When compared with sham control groups (10 trials, n=1534), acupuncture demonstrated a small but statistically significant improvement in headache frequency. Three trials (n=744) compared acupuncture to medication prophylaxis for migraine headaches and found acupuncture had similar effectiveness with fewer adverse effects.¹¹

Osteoarthritis (OA). Most studies have focused on OA of the knee, and, thus far, have generated conflicting results. A Cochrane review in 2010 included 4 trials (n=884) that had a wait list control and 9 trials (n=1835) that compared acupuncture to a sham control.¹² When compared to a wait list control, acupuncture resulted in statistically significant and clinically relevant improvement in pain and function. However, when compared to sham treatment for OA, the review showed statistically significant improvement in pain and function for acupuncture that was unlikely to be clinically relevant.¹²

A more recent meta-analysis in 2016 evaluated 10 trials (N=2007) investigating acupuncture in the treatment of knee OA.¹³ The authors found acupuncture improved both pain and functional outcome measures when compared with either no treatment or a sham control.

Fibromyalgia. Systematic reviews in 2007 (5 trials, N=316)¹⁸ and 2010 (7 trials, N=385)¹⁹ showed that acupuncture did provide short-term pain relief in patients with fibromyalgia, but that the effect was not sustained at follow-up.These reviews were limited by a high risk of bias, which was noted in the studies. The authors of both reviews concluded that acupuncture could not be recommended for the treatment of fibromyalgia.

A more recent Cochrane review published in 2013 (9 trials, N=395) offered low- to moderate-level evidence of benefit for acupuncture compared with no treatment at one month follow-up.¹⁴ Of note, there was also evidence of benefit in improved sleep and global well-being, in addition to pain and stiffness measures in this review. The overall magnitude of benefit was small, but clinically significant. Acupuncture also has evidence of benefit in the treatment of conditions commonly seen in conjunction with fibromyalgia, including headaches and low back pain as described earlier.

3. What does a typical acupuncture treatment entail?

In a typical treatment, anywhere from about 5 to 20 needles are inserted into the body. Common areas of needling include the arms and legs, especially below the elbows and knees. Other frequently used areas are the scalp, ears, and structures related to the painful condition.

The needles used are very thin (typically smaller than a 30-gauge needle) and do not have a beveled tip like phlebotomy needles do. Most patients have minimal pain as the needles are inserted. During the treatment, the needles may be left alone or they may be heated or stimulated electrically. An average treatment lasts 30 to 40 minutes; many patients find the sessions relaxing.

4. Are there any adverse effects or complications of treatment?

Acupuncture is generally considered a safe therapy, with most patients experiencing no adverse effects at all. Minor adverse effects can include post-treatment fatigue, minor bruising, or vasovagal reactions from the insertion of the needles. Serious complications, such as pneumothorax, are possible, but are considered rare.²⁰ A 2004 study estimated the incidence of severe complications to be .05 per 10,000 acupuncture treatments.²¹

Infections are also possible, but most reported cases were due to practitioners reusing needles.²² The standard of care in the United States is to use only sterilized, single-use needles. With this practice, infections due to acupuncture are thought to be rare.

Of note, trials that compare acupuncture to another active therapy often find that acupuncture has fewer adverse effects. This has been the case when acupuncture was compared to NSAIDs for low back pain and to topiramate for headaches.^17,23

5. How does acupuncture fit into a patient’s treatment?

The simple answer is that it is often most effectively used as part of a comprehensive management plan for chronic pain.

As our understanding of the complexity of chronic pain deepens, our therapeutic armamentarium for the management of chronic pain needs to broaden. This was summed up well in a 2016 article on the multimodal management of chronic pain when the authors stated, “Many targets need more than one arrow.”²⁴ Effective management of chronic pain involves addressing psychosocial and lifestyle factors in a patient-centered way and finding a combination of treatments that most effectively leads to improved coping and function.

It’s important to note that like medications and injections, acupuncture is a passive therapy. Although there is evidence for efficacy of improved pain with acupuncture in certain conditions, it should be combined with treatments that actively engage patients, such as exercise, behavioral treatments, development of coping skills, sleep hygiene, and educational strategies.

6. To whom do I refer patients for acupuncture treatment?

In the United States, licensed acupuncturists and physicians most commonly perform acupuncture. There are more than 50 schools that train licensed acupuncturists in the United States, and it usually takes 3 years to meet the requirements.²⁵

Physicians are often trained through continuing medical education (CME) programs that take several months to complete. These programs often combine live lectures, distance learning, and hands-on training and are typically sponsored by a university. Most require 300 hours of CME to complete. Licensure varies by state, but in many states, having an MD or DO degree automatically allows physicians to practice acupuncture. (See “Online resources,” above for links to Web sites that can be useful in finding qualified acupuncturists in your area.)

7. Is acupuncture covered by insurance?

Patients can expect to pay $75 to $150 for an acupuncture session.

It depends. Insurance coverage of acupuncture is highly variable and based on region and insurance type. Medicare and Medicaid plans do not pay for acupuncture. There are some private insurance plans that do. If covered, there may be limitations regarding diagnosis, number of visits, or provider. It is best for patients to call their insurance plan directly to inquire about coverage and any limitations. If paying out of pocket, patients can expect to pay $75 to $150 per treatment session.

CORRESPONDENCE
Russell Lemmon, DO, 1100 Delaplaine Court, Madison, WI 53715; [email protected].

An estimated 39.4 million US adults suffer from persistent pain,¹ and the National Institutes of Health indicate that pain affects more Americans than diabetes, heart disease, and cancer combined.²

As physicians, we know that conventional options to manage chronic pain leave much to be desired and that more evidence-based treatment options are sorely needed. Patients know this, too, and turn to complementary therapies for pain more than for any other diagnosis.³

Case in point: The use of acupuncture is growing. Its use in the United States tripled between 1997 and 2007.⁴ In addition, the research base for acupuncture is rapidly expanding. From 1991 to 2009, nearly 4000 acupuncture research studies were published, with studies on pain accounting for 41% of the acupuncture literature.⁴

But acupuncture is not without controversy. This is due to a lack of a universally accepted biologic mechanism, theories of use and efficacy based in an alternative medical system (traditional Chinese medicine [TCM]), and conflicting views of the evidence.

This article will help make sense of this growing body of knowledge by summarizing the latest evidence and addressing 7 common questions about acupuncture for pain conditions. Applying this information will give you the confidence to counsel patients appropriately and decide if acupuncture fits within their pain management plan.

1. What is acupuncture and how does it work?

Acupuncture, which has a 2000-year history of use, involves inserting needles at various points throughout the body to promote healing and improve function. Although acupuncture represents one piece of TCM (which is a holistic system that also includes herbal medicine, nutrition, meditation, and movement), it is often offered as an independent therapy.

Acupuncture point locations are determined either by using an underlying theoretical framework, such as TCM, or by using anatomic structures, such as muscular trigger points. Providers today often employ a hybrid approach when delivering acupuncture treatment. That is, practitioners may choose point locations based on TCM, but they may combine the practice with local treatments that are based on current knowledge of anatomy. For example, a patient presenting with low back pain may be treated utilizing traditional points located near the ankle and knee, and also by needling active trigger points in the quadratus lumborum muscle.

The mechanism of action. One of the reasons for the continuing controversy surrounding acupuncture is the lack of a clear understanding of its underlying mechanism of action. For centuries the “how” of acupuncture has been explained in poetic terms such as yin, yang, and qi. Only in the past half-century have we begun investigating the potential biologic mechanisms responsible for the physiologic effects seen with acupuncture treatment.

While research has uncovered several interesting theories, how these mechanisms interact to produce therapeutic effects is still unclear. However, looking at various components of the nervous system helps to provide some insight.

Consider the nervous system. One way to conceptualize the mechanisms of acupuncture is to consider the various levels of the nervous system and how each level is affected. In the central nervous system, needling an acupuncture point stimulates the natural endorphin system, altering the pain sensation.⁵ This effect is reversible with naloxone in animal models, indicating that blocking the endorphin system interferes with the analgesic benefits of acupuncture.⁵

Serotonergic systems are also involved centrally. Functional magnetic resonance imaging studies have shown that needling specific acupuncture points modulates areas of the brain.

In the spinal cord, the gate control theory is believed to play a role. (The gate control theory puts forth that nonpainful input closes the “gates” to painful input, which prevents pain sensations from traveling to the central nervous system.) Modulation of sensory input occurs at the level of the dorsal horn of the spinal cord during an acupuncture treatment, which can affect the physiologic pain response.⁶ Opioid receptors are also affected at the spinal cord level.⁷

Acupuncture use in the United States tripled between 1997 and 2007.

Lastly, multiple chemicals released peripherally, including interleukins, substance P, and adenosine, appear to contribute to acupuncture’s analgesia.⁶ We know this because a local anesthetic injected around a peripheral nerve at an acupoint blocks the analgesic effect of acupuncture.⁸ Taken together, acupuncture treatment produces physiologic changes in the brain, spinal cord, and at the periphery, making it a truly unique therapeutic modality.

2. Is acupuncture an effective treatment for pain?

Yes, but before we look at the individual studies, it is important to mention some of the shortcomings of the research to date. First, acupuncture trials lack a standard sham control intervention. Some sham treatments involve skin penetration, while others do not. This has led to controversy regarding whether the sham interventions themselves are physiologically active, thus lessening the magnitude of effect for acupuncture. This is a point of contention in the acupuncture literature and a factor to consider when deciding if results have clinical significance.

In addition, the acupuncturist providing treatment in a trial is typically unblinded. This is also true of trials measuring other physical modalities, but it contributes to the debate surrounding the magnitude of placebo response in acupuncture studies.

Finally, many randomized trials involving acupuncture have had low methodologic quality. Fortunately, there are now several high-quality systematic reviews that have attempted to filter out the lower-quality research and provide a better representation of the evidence (TABLE^9-14). A discussion of them follows.

General chronic pain. A 2012 meta-analysis¹⁵ evaluated the effectiveness of acupuncture for the treatment of chronic pain with one of 4 etiologies: nonspecific back or neck pain, chronic headache, osteoarthritis, and shoulder pain. This analysis attempted to control for the high variability of study quality in the acupuncture literature by including only studies of high methodologic character. The final analysis included 29 randomized controlled trials (N=17,922). The authors concluded that acupuncture was superior to both no acupuncture and sham (placebo) acupuncture for all pain conditions in the study. The average effect size was 0.5 standard deviations on a 10-point scale. The authors considered this to be clinically relevant, although the magnitude of benefit was modest.¹⁵

Low back pain. A 2017 systematic review by Chou et al⁹ evaluated 32 trials (N=5931) reviewing acupuncture for the treatment of chronic low back pain. This review found acupuncture was associated with lower pain intensity and improved function in the short term when compared with no treatment. And while acupuncture was associated with lower pain intensity when compared with a sham control, there was no difference in function between the 2 groups. Of note, 3 of the included trials compared acupuncture to standard medications used in the treatment of low back pain and found acupuncture to be superior in terms of both pain reduction and improved function.⁹

Trials that compared acupuncture to another active therapy have found that it often has fewer adverse effects.

The authors of a 2008 systematic review that evaluated 23 trials (N=6359)¹⁰ similarly concluded that there is moderate evidence for the use of acupuncture (compared to no treatment) for the treatment of nonspecific low back pain, but did not find evidence that acupuncture was superior to sham controls.¹⁰ The 2017 American College of Physicians clinical practice guidelines support the use of acupuncture for the treatment of chronic low back pain.¹⁶

In addition to helping with chronic low back pain, acupuncture is also showing promise as a treatment for acute spinal pain. A 2013 systematic review (11 trials, N=1139) showed that acupuncture may be more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) in treating acute low back pain and may cause fewer adverse effects.¹⁷

Headache pain. Evidence favoring acupuncture in the management of headache has been fairly consistent over the past decade. An updated Cochrane review on the prevention of migraine headaches was published in 2016.¹¹ Acupuncture was compared with no treatment in 4 trials (n=2199). The authors found moderate quality evidence that acupuncture reduces headache frequency (number needed to treat=4). Acupuncture achieved at least 50% headache reduction in 41% vs 17% in the groups that received no acupuncture. When compared with sham control groups (10 trials, n=1534), acupuncture demonstrated a small but statistically significant improvement in headache frequency. Three trials (n=744) compared acupuncture to medication prophylaxis for migraine headaches and found acupuncture had similar effectiveness with fewer adverse effects.¹¹

Osteoarthritis (OA). Most studies have focused on OA of the knee, and, thus far, have generated conflicting results. A Cochrane review in 2010 included 4 trials (n=884) that had a wait list control and 9 trials (n=1835) that compared acupuncture to a sham control.¹² When compared to a wait list control, acupuncture resulted in statistically significant and clinically relevant improvement in pain and function. However, when compared to sham treatment for OA, the review showed statistically significant improvement in pain and function for acupuncture that was unlikely to be clinically relevant.¹²

A more recent meta-analysis in 2016 evaluated 10 trials (N=2007) investigating acupuncture in the treatment of knee OA.¹³ The authors found acupuncture improved both pain and functional outcome measures when compared with either no treatment or a sham control.

Fibromyalgia. Systematic reviews in 2007 (5 trials, N=316)¹⁸ and 2010 (7 trials, N=385)¹⁹ showed that acupuncture did provide short-term pain relief in patients with fibromyalgia, but that the effect was not sustained at follow-up.These reviews were limited by a high risk of bias, which was noted in the studies. The authors of both reviews concluded that acupuncture could not be recommended for the treatment of fibromyalgia.

A more recent Cochrane review published in 2013 (9 trials, N=395) offered low- to moderate-level evidence of benefit for acupuncture compared with no treatment at one month follow-up.¹⁴ Of note, there was also evidence of benefit in improved sleep and global well-being, in addition to pain and stiffness measures in this review. The overall magnitude of benefit was small, but clinically significant. Acupuncture also has evidence of benefit in the treatment of conditions commonly seen in conjunction with fibromyalgia, including headaches and low back pain as described earlier.

3. What does a typical acupuncture treatment entail?

In a typical treatment, anywhere from about 5 to 20 needles are inserted into the body. Common areas of needling include the arms and legs, especially below the elbows and knees. Other frequently used areas are the scalp, ears, and structures related to the painful condition.

The needles used are very thin (typically smaller than a 30-gauge needle) and do not have a beveled tip like phlebotomy needles do. Most patients have minimal pain as the needles are inserted. During the treatment, the needles may be left alone or they may be heated or stimulated electrically. An average treatment lasts 30 to 40 minutes; many patients find the sessions relaxing.

4. Are there any adverse effects or complications of treatment?

Acupuncture is generally considered a safe therapy, with most patients experiencing no adverse effects at all. Minor adverse effects can include post-treatment fatigue, minor bruising, or vasovagal reactions from the insertion of the needles. Serious complications, such as pneumothorax, are possible, but are considered rare.²⁰ A 2004 study estimated the incidence of severe complications to be .05 per 10,000 acupuncture treatments.²¹

Infections are also possible, but most reported cases were due to practitioners reusing needles.²² The standard of care in the United States is to use only sterilized, single-use needles. With this practice, infections due to acupuncture are thought to be rare.

Of note, trials that compare acupuncture to another active therapy often find that acupuncture has fewer adverse effects. This has been the case when acupuncture was compared to NSAIDs for low back pain and to topiramate for headaches.^17,23

5. How does acupuncture fit into a patient’s treatment?

The simple answer is that it is often most effectively used as part of a comprehensive management plan for chronic pain.

As our understanding of the complexity of chronic pain deepens, our therapeutic armamentarium for the management of chronic pain needs to broaden. This was summed up well in a 2016 article on the multimodal management of chronic pain when the authors stated, “Many targets need more than one arrow.”²⁴ Effective management of chronic pain involves addressing psychosocial and lifestyle factors in a patient-centered way and finding a combination of treatments that most effectively leads to improved coping and function.

It’s important to note that like medications and injections, acupuncture is a passive therapy. Although there is evidence for efficacy of improved pain with acupuncture in certain conditions, it should be combined with treatments that actively engage patients, such as exercise, behavioral treatments, development of coping skills, sleep hygiene, and educational strategies.

6. To whom do I refer patients for acupuncture treatment?

In the United States, licensed acupuncturists and physicians most commonly perform acupuncture. There are more than 50 schools that train licensed acupuncturists in the United States, and it usually takes 3 years to meet the requirements.²⁵

Physicians are often trained through continuing medical education (CME) programs that take several months to complete. These programs often combine live lectures, distance learning, and hands-on training and are typically sponsored by a university. Most require 300 hours of CME to complete. Licensure varies by state, but in many states, having an MD or DO degree automatically allows physicians to practice acupuncture. (See “Online resources,” above for links to Web sites that can be useful in finding qualified acupuncturists in your area.)

7. Is acupuncture covered by insurance?

Patients can expect to pay $75 to $150 for an acupuncture session.

It depends. Insurance coverage of acupuncture is highly variable and based on region and insurance type. Medicare and Medicaid plans do not pay for acupuncture. There are some private insurance plans that do. If covered, there may be limitations regarding diagnosis, number of visits, or provider. It is best for patients to call their insurance plan directly to inquire about coverage and any limitations. If paying out of pocket, patients can expect to pay $75 to $150 per treatment session.

CORRESPONDENCE
Russell Lemmon, DO, 1100 Delaplaine Court, Madison, WI 53715; [email protected].

ABSTRACT

Purpose This study evaluated the effect of patient positioning on the diagnosis of hypertension in a clinic setting and the importance of following guidelines for measuring blood pressure (BP).

Methods In the trial part of this study, we recorded BP measurements by an aneroid sphygmomanometer with patients seated first on an examination table, a commonly observed practice, and second in the standard seated position as defined by the American Heart Association. Two measurements were obtained in each position for 204 patients, and we determined the difference between the average readings in the 2 positions. Factored into the comparison was an estimation of inherent variance of the device and observer achieved by repeated measurements on a healthy individual.

Results This investigation included an initial observational study of 25 regional primary care offices, the results of which showed frequent lack of adherence with accepted guidelines in patient positioning during BP measurement. The overall systolic and diastolic BPs were more than 2 mm Hg lower in the standard seated position compared with the examination table position (P<.001). Noncompliance with the position guideline resulted in misclassification of 15 patients (7.4%) as prehypertensive, when, in fact, they were normotensive. Misclassification of hypertension occurred in 12 patients (5.9%), when, in fact, they were normotensive. Logistic regression using relevant clinical factors did not identify those individuals who were misclassified.

Conclusion This study underscores the importance of patient positioning on BP determinations in order to accurately diagnose hypertension.

The high prevalence of hypertension and its burden of disease in the United States and worldwide are well known.¹ Hypertension is a major risk factor for coronary heart disease, congestive heart failure, ischemic and hemorrhagic stroke, chronic kidney disease, and peripheral arterial disease.² Among all risk factors, hypertension ranked first worldwide in disability-adjusted life-years.³ However, misclassification of an individual’s blood pressure (BP) as prehypertension or hypertension also confers significant health and financial burdens due to unnecessary medical encounters, testing, and treatment, and to increased cost of insurance coverage and out-of-pocket expenses. A correct assessment of BP in the outpatient setting depends on accurate measurement technique.

The diagnosis of hypertension is based on indirect measurement of BP using in-office, ambulatory, or home monitoring. Although office BP measurement is less than ideal, it is used most often to diagnose and monitor hypertension. Furthermore, most published trials of treatment recommendations are based on office BP measurements.⁴

Automated oscillometric and aneroid sphygmomanometers are common BP measurement devices. Proper technique is particularly important with the aneroid sphygmomanometer to obtain consistent and accurate results.⁵ Good training and an ability to hear the Korotkoff sounds are crucial.

Only 10 of 25 offices we visited in our area measured BP with patients properly seated in a chair. Most had their patients sit on the edge of the examination table.

Expert consensus groups such as the American Heart Association (AHA) publish recommendations for proper technique in reliably measuring BP,^6-8 and they emphasize the importance of patient positioning during BP measurement. The individual should be seated comfortably in a chair with both arms and back supported, legs uncrossed, and feet flat on the floor. We’ll refer to this as the “standard position.” Although the proper technique for measuring BP has been widely advocated, a recent literature review for the US Preventive Services Task Force concluded that surprisingly few studies are available on the diagnostic accuracy of office BP practices.⁹

One paper evaluated the effect of leg crossing on accuracy of BP measurement. No subjects were reclassified as hypertensive, but the study lacked statistical rigor.¹⁰ Another study found variable BP readings regardless of body position.¹¹

The purpose of our study was to compare BP measurement in 2 positions: the standard position described above, and the examination table position in which the patient is seated on the edge of the table with back, arms, and feet unsupported.

METHODS

We conducted our literature search across several scientific and medical literature databases, including PubMed, ScienceDirect, and CINAHL. Only English-language articles were reviewed.

We followed the BP measurement guidelines of the AHA. Prior to beginning the study, we provided instructions in proper BP measurement technique to the nurses who would obtain the data. The minimum sample size of patients needed to identify a difference of at least 2 mm Hg was 26, as estimated by power analysis. This was calculated using an alpha of .05 and a beta of .13.

The study population consisted of patients presenting consecutively to a teaching family medicine center. Adult patients, ages 18 and older, were informed about the study and invited to participate. Those who agreed were asked to read and sign an informed consent approved by a regional institutional review board for human subjects. We excluded patients who declined participation for any reason, who were in severe pain or distress that may have prevented them from completing the protocol, or who had limited mobility that could interfere with climbing onto the examination table. Patients considered for the study totaled 250, 28 of whom were ineligible. Another 18 patients declined participation, leaving 204 who completed the protocol.

Before testing began, we estimated the standard deviation of each aneroid sphygmomanometer and the assigned observer by repeatedly measuring the BP of a healthy normotensive individual sitting in the standard position. We obtained 46 measurements over 2 days to avoid subject and operator fatigue. Standard deviation for systolic BP was 3.6 mm Hg; for diastolic it was 3.8 mm Hg.

During testing, nurses recorded BP for each patient twice in the examination table position and twice in the standard position. They entered data into an Excel workbook for subsequent analysis. All examination rooms were equipped with newly purchased aneroid sphygmomanometers, and the appropriate cuff size was selected for each patient. Patients were instructed to remain quiet during the measurements. Patients sat first on the edge of the examination table. After a 5-minute rest, BP was measured twice in the same arm. Measurements were separated by 1 to 2 minutes. Patients then sat in the chair and rested another 2 minutes before BP was again measured twice in the same arm. The arms and back were supported in the chair and the stethoscope placed at heart level.

As per protocol, we obtained 4 BP readings on each patient and calculated the difference between the average systolic and diastolic BP values from the 2 positions. The standard error of the mean of this difference was determined using the equation, where Sd is the standard deviation of the aneroid sphygmomanometer and observer.¹² A one-sided, 95% confidence upper bound for the standard error of the difference is 1.65 × SEd. We compared patient-specific differences against this upper bound to identify significant systolic and diastolic BP changes due to positioning. If the patient’s BP difference exceeded the upper bound, it was attributed to the positional change and not to variation inherent to the sphygmomanometer and observer.

As an example, consider a patient whose average systolic BP readings from the examination-table and standard positions, respectively, were 128 mm Hg and 120 mm Hg. Assuming an SEd of 3.55 and an upper bound of 5.86, the observed 8 mm Hg difference in average systolic BPs would be considered significant. The amount of random variation from the sphygmomanometer and observer would not be expected to exceed 5.86 mm Hg.

In accordance with accepted standards, prehypertension was defined as a BP between 120-139/80-89 mm Hg, and hypertension was defined as a BP ≥140/90 mm Hg.⁴ BP below 120/80 mm Hg was considered normal. We calculated each patient’s average systolic and diastolic BP values in the 2 positions and thereby classified the individual as normotensive, prehypertensive, or hypertensive. We regarded as misclassified any patient whose BP showed significant lowering between the examination-table and standard positions resulting in a change of classification from prehypertensive or hypertensive to normotensive. For example, a patient with an examination-table position average reading of 126/85 mm Hg and a standard position average reading of 118/78 mm Hg would have been misclassified as prehypertensive.

We reviewed charts and gathered data, including subject age, sex, obesity (defined as a body mass index of ≥30 kg/m²), and history of diabetes, hypertension, or smoking. Other than age, all data were binary. We performed logistic regression analysis using the Excel Add-in Real Statistics Resource Pack software (Release 4.3)¹³ to determine if these factors could predict significant lowering of BP due to positional change.

Our associated observational study. We also conducted a separate observational study of 25 regional primary care offices to evaluate compliance with the AHA guidelines for measuring BP. The office nurses taking measurements were not informed of the study’s purpose to prevent deviation from their common practice.

In our study, 13.2% of patients classified as prehypertensive or hypertensive when they sat on the exam table were found to be normotensive when seated in the chair.

Data on 9 guideline criteria were collected to assess supervision of patients before and during measurements, including having the patient sit in a chair in quiet and comfortable surroundings with arms and back supported and feet on the ground. We also noted the type of BP measuring device used. Additionally, observers assessed the technique of the individuals using a manual device, including cuff placement and deflation rate. The observations were conducted during a clinic visit by a medical student knowledgeable in the AHA guidelines for measuring BP by automated oscillometric or aneroid sphygmomanometric devices. We conducted the study over a 2-week period in the second quarter of 2016.

RESULTS

Power analysis performed prior to the study showed that a minimum of 26 patients would be needed to predict a 2 mm Hg difference between BPs obtained in the 2 positions. Of the 204 patients used in the logistic regression analysis, 78 were men and 126 were women. Ages ranged from 18 to 101 years, yielding a mean of 54. One-hundred sixteen had previously received a diagnosis of hypertension, 39 had diabetes, 92 were obese, 22 were current smokers, and 68 were former smokers.

TABLE 1 shows the means and ranges of systolic and diastolic BP for both study positions. With this study population, mean BP recorded in the examination-table position decreased in the standard position by 2.1 and 2.2 mm Hg for systolic and diastolic BP, respectively (P<.001).

Significant BP lowering—as defined by a one-sided 95% confidence upper bound for the standard error of differences between study positions—was determined to be 5.86 and 6.22 mm Hg for systolic and diastolic pressures, respectively. Significant lowering of BP and misclassification due to positioning are summarized in TABLE 2. Significant lowering of mean systolic or diastolic BP with positional change from table to chair occurred in 62 subjects (30.4%). Misclassification of prehypertension occurred in 7.4% of subjects, and misclassification of hypertension occurred in 5.9%.

Logistic regression using patient age, sex, obesity, and history of diabetes, hypertension, and smoking as independent factors did not predict significant BP lowering with positional change.

Our observational study revealed that proper positioning in a chair was followed in only 10 of the 25 offices. In the remaining offices, patients were seated on the examination table. A 5-minute rest period before measuring BP was allowed in only 10 of the 25 offices. An automated oscillometric device was used in only 2 of the 25 offices.

DISCUSSION

In this study, 27 subjects (13.2%) were misclassified as prehypertensive or hypertensive as a result of deviating from the standard position in obtaining BP. Although the standard position is universally recommended, the guideline is not always followed in clinical practice.¹⁴

One study by Villegas et al found that 60% of physicians and nurses working in a major hospital were measuring BP inaccurately.¹⁵ In our initial observational study, 60% of primary care practices visited did not adhere to the recommended patient positioning. These medical offices are located in the community surrounding our facility and are operated by the same health care organization. The misclassification of prehypertension and hypertension observed in our prospective comparison of BP recordings in table and chair positions is, therefore, likely to occur to some degree at these practices, as well.

Similar diagnostic misclassifications have been reported in other medical settings. In a published survey of 114 medical offices, McKay and coworkers noted frequent inconsistencies with published guidelines in measuring BP.¹⁶

Common clinical demographic data obtained during this study showed no association with the positional BP change. Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of elevated BP for this subgroup of individuals. Measuring muscle tension of the arms and back while seated on an exam table and chair was beyond the scope of this study.

In clinical practice, different types of BP measuring devices are used. Calibration and quality control of these devices is often lacking.¹⁷ Before starting our study, we determined the statistical variance of the aneroid sphygmomanometers and found it to approximate the manufacturer’s precision specification. Guidelines recommend using the mean of 2 BP readings as representing the patient’s BP for a given clinic visit. Additional readings are recommended if there is more than a 5 mm Hg difference between the initial 2 readings.⁴

In our study, we used sampling statistics of the BP readings and clinical guideline BP ranges in making diagnostic determinations. The inability to identify those patients whose BP will be affected by positional change highlights the importance of following standard BP measurement guidelines for all patients.

Study limitations. Positional change in BP from examination table to chair lacks a comparison to BP changes in positioning from chair to table. If similar BP changes in the reverse sequence were to be observed, this would add support to the hypothesis that muscle tension of the unsupported body is a cause of BP elevation in certain individuals. We believe, however, that the sequence of BP measurements (from table to chair) did not have a significant impact because all patients were allowed to rest in each position before the BP was measured. The BP was therefore measured in a steady-state in both positions.

Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of the elevated BP.

Additionally, BP measurement by aneroid sphygmomanometry is highly dependent on observer skill and hearing ability. Furthermore, a disproportionate number of BP measurements recorded in the study ended in zero, suggesting terminal digit bias by the observer. These sources of error may be avoided using an automated oscillometric measuring device.¹⁸ Automated devices also allow for repeated independent measurements that minimize the white-coat effect. However, there are also limitations to the accuracy of oscillometric equipment. This is especially true when recording BP in the elderly, a group whose stiff arterial walls may cause erroneous measurements.¹⁹

Guideline justification. Nonadherence to standard positioning when measuring BP leads to certain individuals being misclassified as prehypertensive or hypertensive. Misclassification in turn leads to unnecessary medical encounters, testing, and treatment. Misdiagnosis is also likely to increase the cost of an individual’s insurance coverage and out-of-pocket health care expenses.

CORRESPONDENCE
Roy N. Morcos, MD, St. Elizabeth Family Medicine Residency Program, 8423 Market Street, Suite 101, Boardman, Ohio 44512; [email protected].

ABSTRACT

Purpose This study evaluated the effect of patient positioning on the diagnosis of hypertension in a clinic setting and the importance of following guidelines for measuring blood pressure (BP).

Methods In the trial part of this study, we recorded BP measurements by an aneroid sphygmomanometer with patients seated first on an examination table, a commonly observed practice, and second in the standard seated position as defined by the American Heart Association. Two measurements were obtained in each position for 204 patients, and we determined the difference between the average readings in the 2 positions. Factored into the comparison was an estimation of inherent variance of the device and observer achieved by repeated measurements on a healthy individual.

Results This investigation included an initial observational study of 25 regional primary care offices, the results of which showed frequent lack of adherence with accepted guidelines in patient positioning during BP measurement. The overall systolic and diastolic BPs were more than 2 mm Hg lower in the standard seated position compared with the examination table position (P<.001). Noncompliance with the position guideline resulted in misclassification of 15 patients (7.4%) as prehypertensive, when, in fact, they were normotensive. Misclassification of hypertension occurred in 12 patients (5.9%), when, in fact, they were normotensive. Logistic regression using relevant clinical factors did not identify those individuals who were misclassified.

Conclusion This study underscores the importance of patient positioning on BP determinations in order to accurately diagnose hypertension.

The high prevalence of hypertension and its burden of disease in the United States and worldwide are well known.¹ Hypertension is a major risk factor for coronary heart disease, congestive heart failure, ischemic and hemorrhagic stroke, chronic kidney disease, and peripheral arterial disease.² Among all risk factors, hypertension ranked first worldwide in disability-adjusted life-years.³ However, misclassification of an individual’s blood pressure (BP) as prehypertension or hypertension also confers significant health and financial burdens due to unnecessary medical encounters, testing, and treatment, and to increased cost of insurance coverage and out-of-pocket expenses. A correct assessment of BP in the outpatient setting depends on accurate measurement technique.

The diagnosis of hypertension is based on indirect measurement of BP using in-office, ambulatory, or home monitoring. Although office BP measurement is less than ideal, it is used most often to diagnose and monitor hypertension. Furthermore, most published trials of treatment recommendations are based on office BP measurements.⁴

Automated oscillometric and aneroid sphygmomanometers are common BP measurement devices. Proper technique is particularly important with the aneroid sphygmomanometer to obtain consistent and accurate results.⁵ Good training and an ability to hear the Korotkoff sounds are crucial.

Only 10 of 25 offices we visited in our area measured BP with patients properly seated in a chair. Most had their patients sit on the edge of the examination table.

Expert consensus groups such as the American Heart Association (AHA) publish recommendations for proper technique in reliably measuring BP,^6-8 and they emphasize the importance of patient positioning during BP measurement. The individual should be seated comfortably in a chair with both arms and back supported, legs uncrossed, and feet flat on the floor. We’ll refer to this as the “standard position.” Although the proper technique for measuring BP has been widely advocated, a recent literature review for the US Preventive Services Task Force concluded that surprisingly few studies are available on the diagnostic accuracy of office BP practices.⁹

One paper evaluated the effect of leg crossing on accuracy of BP measurement. No subjects were reclassified as hypertensive, but the study lacked statistical rigor.¹⁰ Another study found variable BP readings regardless of body position.¹¹

The purpose of our study was to compare BP measurement in 2 positions: the standard position described above, and the examination table position in which the patient is seated on the edge of the table with back, arms, and feet unsupported.

METHODS

We conducted our literature search across several scientific and medical literature databases, including PubMed, ScienceDirect, and CINAHL. Only English-language articles were reviewed.

We followed the BP measurement guidelines of the AHA. Prior to beginning the study, we provided instructions in proper BP measurement technique to the nurses who would obtain the data. The minimum sample size of patients needed to identify a difference of at least 2 mm Hg was 26, as estimated by power analysis. This was calculated using an alpha of .05 and a beta of .13.

The study population consisted of patients presenting consecutively to a teaching family medicine center. Adult patients, ages 18 and older, were informed about the study and invited to participate. Those who agreed were asked to read and sign an informed consent approved by a regional institutional review board for human subjects. We excluded patients who declined participation for any reason, who were in severe pain or distress that may have prevented them from completing the protocol, or who had limited mobility that could interfere with climbing onto the examination table. Patients considered for the study totaled 250, 28 of whom were ineligible. Another 18 patients declined participation, leaving 204 who completed the protocol.

Before testing began, we estimated the standard deviation of each aneroid sphygmomanometer and the assigned observer by repeatedly measuring the BP of a healthy normotensive individual sitting in the standard position. We obtained 46 measurements over 2 days to avoid subject and operator fatigue. Standard deviation for systolic BP was 3.6 mm Hg; for diastolic it was 3.8 mm Hg.

During testing, nurses recorded BP for each patient twice in the examination table position and twice in the standard position. They entered data into an Excel workbook for subsequent analysis. All examination rooms were equipped with newly purchased aneroid sphygmomanometers, and the appropriate cuff size was selected for each patient. Patients were instructed to remain quiet during the measurements. Patients sat first on the edge of the examination table. After a 5-minute rest, BP was measured twice in the same arm. Measurements were separated by 1 to 2 minutes. Patients then sat in the chair and rested another 2 minutes before BP was again measured twice in the same arm. The arms and back were supported in the chair and the stethoscope placed at heart level.

As per protocol, we obtained 4 BP readings on each patient and calculated the difference between the average systolic and diastolic BP values from the 2 positions. The standard error of the mean of this difference was determined using the equation, where Sd is the standard deviation of the aneroid sphygmomanometer and observer.¹² A one-sided, 95% confidence upper bound for the standard error of the difference is 1.65 × SEd. We compared patient-specific differences against this upper bound to identify significant systolic and diastolic BP changes due to positioning. If the patient’s BP difference exceeded the upper bound, it was attributed to the positional change and not to variation inherent to the sphygmomanometer and observer.

As an example, consider a patient whose average systolic BP readings from the examination-table and standard positions, respectively, were 128 mm Hg and 120 mm Hg. Assuming an SEd of 3.55 and an upper bound of 5.86, the observed 8 mm Hg difference in average systolic BPs would be considered significant. The amount of random variation from the sphygmomanometer and observer would not be expected to exceed 5.86 mm Hg.

In accordance with accepted standards, prehypertension was defined as a BP between 120-139/80-89 mm Hg, and hypertension was defined as a BP ≥140/90 mm Hg.⁴ BP below 120/80 mm Hg was considered normal. We calculated each patient’s average systolic and diastolic BP values in the 2 positions and thereby classified the individual as normotensive, prehypertensive, or hypertensive. We regarded as misclassified any patient whose BP showed significant lowering between the examination-table and standard positions resulting in a change of classification from prehypertensive or hypertensive to normotensive. For example, a patient with an examination-table position average reading of 126/85 mm Hg and a standard position average reading of 118/78 mm Hg would have been misclassified as prehypertensive.

We reviewed charts and gathered data, including subject age, sex, obesity (defined as a body mass index of ≥30 kg/m²), and history of diabetes, hypertension, or smoking. Other than age, all data were binary. We performed logistic regression analysis using the Excel Add-in Real Statistics Resource Pack software (Release 4.3)¹³ to determine if these factors could predict significant lowering of BP due to positional change.

Our associated observational study. We also conducted a separate observational study of 25 regional primary care offices to evaluate compliance with the AHA guidelines for measuring BP. The office nurses taking measurements were not informed of the study’s purpose to prevent deviation from their common practice.

In our study, 13.2% of patients classified as prehypertensive or hypertensive when they sat on the exam table were found to be normotensive when seated in the chair.

Data on 9 guideline criteria were collected to assess supervision of patients before and during measurements, including having the patient sit in a chair in quiet and comfortable surroundings with arms and back supported and feet on the ground. We also noted the type of BP measuring device used. Additionally, observers assessed the technique of the individuals using a manual device, including cuff placement and deflation rate. The observations were conducted during a clinic visit by a medical student knowledgeable in the AHA guidelines for measuring BP by automated oscillometric or aneroid sphygmomanometric devices. We conducted the study over a 2-week period in the second quarter of 2016.

RESULTS

Power analysis performed prior to the study showed that a minimum of 26 patients would be needed to predict a 2 mm Hg difference between BPs obtained in the 2 positions. Of the 204 patients used in the logistic regression analysis, 78 were men and 126 were women. Ages ranged from 18 to 101 years, yielding a mean of 54. One-hundred sixteen had previously received a diagnosis of hypertension, 39 had diabetes, 92 were obese, 22 were current smokers, and 68 were former smokers.

TABLE 1 shows the means and ranges of systolic and diastolic BP for both study positions. With this study population, mean BP recorded in the examination-table position decreased in the standard position by 2.1 and 2.2 mm Hg for systolic and diastolic BP, respectively (P<.001).

Significant BP lowering—as defined by a one-sided 95% confidence upper bound for the standard error of differences between study positions—was determined to be 5.86 and 6.22 mm Hg for systolic and diastolic pressures, respectively. Significant lowering of BP and misclassification due to positioning are summarized in TABLE 2. Significant lowering of mean systolic or diastolic BP with positional change from table to chair occurred in 62 subjects (30.4%). Misclassification of prehypertension occurred in 7.4% of subjects, and misclassification of hypertension occurred in 5.9%.

Logistic regression using patient age, sex, obesity, and history of diabetes, hypertension, and smoking as independent factors did not predict significant BP lowering with positional change.

Our observational study revealed that proper positioning in a chair was followed in only 10 of the 25 offices. In the remaining offices, patients were seated on the examination table. A 5-minute rest period before measuring BP was allowed in only 10 of the 25 offices. An automated oscillometric device was used in only 2 of the 25 offices.

DISCUSSION

In this study, 27 subjects (13.2%) were misclassified as prehypertensive or hypertensive as a result of deviating from the standard position in obtaining BP. Although the standard position is universally recommended, the guideline is not always followed in clinical practice.¹⁴

One study by Villegas et al found that 60% of physicians and nurses working in a major hospital were measuring BP inaccurately.¹⁵ In our initial observational study, 60% of primary care practices visited did not adhere to the recommended patient positioning. These medical offices are located in the community surrounding our facility and are operated by the same health care organization. The misclassification of prehypertension and hypertension observed in our prospective comparison of BP recordings in table and chair positions is, therefore, likely to occur to some degree at these practices, as well.

Similar diagnostic misclassifications have been reported in other medical settings. In a published survey of 114 medical offices, McKay and coworkers noted frequent inconsistencies with published guidelines in measuring BP.¹⁶

Common clinical demographic data obtained during this study showed no association with the positional BP change. Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of elevated BP for this subgroup of individuals. Measuring muscle tension of the arms and back while seated on an exam table and chair was beyond the scope of this study.

In clinical practice, different types of BP measuring devices are used. Calibration and quality control of these devices is often lacking.¹⁷ Before starting our study, we determined the statistical variance of the aneroid sphygmomanometers and found it to approximate the manufacturer’s precision specification. Guidelines recommend using the mean of 2 BP readings as representing the patient’s BP for a given clinic visit. Additional readings are recommended if there is more than a 5 mm Hg difference between the initial 2 readings.⁴

In our study, we used sampling statistics of the BP readings and clinical guideline BP ranges in making diagnostic determinations. The inability to identify those patients whose BP will be affected by positional change highlights the importance of following standard BP measurement guidelines for all patients.

Study limitations. Positional change in BP from examination table to chair lacks a comparison to BP changes in positioning from chair to table. If similar BP changes in the reverse sequence were to be observed, this would add support to the hypothesis that muscle tension of the unsupported body is a cause of BP elevation in certain individuals. We believe, however, that the sequence of BP measurements (from table to chair) did not have a significant impact because all patients were allowed to rest in each position before the BP was measured. The BP was therefore measured in a steady-state in both positions.

Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of the elevated BP.

Additionally, BP measurement by aneroid sphygmomanometry is highly dependent on observer skill and hearing ability. Furthermore, a disproportionate number of BP measurements recorded in the study ended in zero, suggesting terminal digit bias by the observer. These sources of error may be avoided using an automated oscillometric measuring device.¹⁸ Automated devices also allow for repeated independent measurements that minimize the white-coat effect. However, there are also limitations to the accuracy of oscillometric equipment. This is especially true when recording BP in the elderly, a group whose stiff arterial walls may cause erroneous measurements.¹⁹

Guideline justification. Nonadherence to standard positioning when measuring BP leads to certain individuals being misclassified as prehypertensive or hypertensive. Misclassification in turn leads to unnecessary medical encounters, testing, and treatment. Misdiagnosis is also likely to increase the cost of an individual’s insurance coverage and out-of-pocket health care expenses.

CORRESPONDENCE
Roy N. Morcos, MD, St. Elizabeth Family Medicine Residency Program, 8423 Market Street, Suite 101, Boardman, Ohio 44512; [email protected].

ABSTRACT

Purpose This study evaluated the effect of patient positioning on the diagnosis of hypertension in a clinic setting and the importance of following guidelines for measuring blood pressure (BP).

Methods In the trial part of this study, we recorded BP measurements by an aneroid sphygmomanometer with patients seated first on an examination table, a commonly observed practice, and second in the standard seated position as defined by the American Heart Association. Two measurements were obtained in each position for 204 patients, and we determined the difference between the average readings in the 2 positions. Factored into the comparison was an estimation of inherent variance of the device and observer achieved by repeated measurements on a healthy individual.

Results This investigation included an initial observational study of 25 regional primary care offices, the results of which showed frequent lack of adherence with accepted guidelines in patient positioning during BP measurement. The overall systolic and diastolic BPs were more than 2 mm Hg lower in the standard seated position compared with the examination table position (P<.001). Noncompliance with the position guideline resulted in misclassification of 15 patients (7.4%) as prehypertensive, when, in fact, they were normotensive. Misclassification of hypertension occurred in 12 patients (5.9%), when, in fact, they were normotensive. Logistic regression using relevant clinical factors did not identify those individuals who were misclassified.

Conclusion This study underscores the importance of patient positioning on BP determinations in order to accurately diagnose hypertension.

The high prevalence of hypertension and its burden of disease in the United States and worldwide are well known.¹ Hypertension is a major risk factor for coronary heart disease, congestive heart failure, ischemic and hemorrhagic stroke, chronic kidney disease, and peripheral arterial disease.² Among all risk factors, hypertension ranked first worldwide in disability-adjusted life-years.³ However, misclassification of an individual’s blood pressure (BP) as prehypertension or hypertension also confers significant health and financial burdens due to unnecessary medical encounters, testing, and treatment, and to increased cost of insurance coverage and out-of-pocket expenses. A correct assessment of BP in the outpatient setting depends on accurate measurement technique.

The diagnosis of hypertension is based on indirect measurement of BP using in-office, ambulatory, or home monitoring. Although office BP measurement is less than ideal, it is used most often to diagnose and monitor hypertension. Furthermore, most published trials of treatment recommendations are based on office BP measurements.⁴

Automated oscillometric and aneroid sphygmomanometers are common BP measurement devices. Proper technique is particularly important with the aneroid sphygmomanometer to obtain consistent and accurate results.⁵ Good training and an ability to hear the Korotkoff sounds are crucial.

Only 10 of 25 offices we visited in our area measured BP with patients properly seated in a chair. Most had their patients sit on the edge of the examination table.

Expert consensus groups such as the American Heart Association (AHA) publish recommendations for proper technique in reliably measuring BP,^6-8 and they emphasize the importance of patient positioning during BP measurement. The individual should be seated comfortably in a chair with both arms and back supported, legs uncrossed, and feet flat on the floor. We’ll refer to this as the “standard position.” Although the proper technique for measuring BP has been widely advocated, a recent literature review for the US Preventive Services Task Force concluded that surprisingly few studies are available on the diagnostic accuracy of office BP practices.⁹

One paper evaluated the effect of leg crossing on accuracy of BP measurement. No subjects were reclassified as hypertensive, but the study lacked statistical rigor.¹⁰ Another study found variable BP readings regardless of body position.¹¹

The purpose of our study was to compare BP measurement in 2 positions: the standard position described above, and the examination table position in which the patient is seated on the edge of the table with back, arms, and feet unsupported.

METHODS

We conducted our literature search across several scientific and medical literature databases, including PubMed, ScienceDirect, and CINAHL. Only English-language articles were reviewed.

We followed the BP measurement guidelines of the AHA. Prior to beginning the study, we provided instructions in proper BP measurement technique to the nurses who would obtain the data. The minimum sample size of patients needed to identify a difference of at least 2 mm Hg was 26, as estimated by power analysis. This was calculated using an alpha of .05 and a beta of .13.

The study population consisted of patients presenting consecutively to a teaching family medicine center. Adult patients, ages 18 and older, were informed about the study and invited to participate. Those who agreed were asked to read and sign an informed consent approved by a regional institutional review board for human subjects. We excluded patients who declined participation for any reason, who were in severe pain or distress that may have prevented them from completing the protocol, or who had limited mobility that could interfere with climbing onto the examination table. Patients considered for the study totaled 250, 28 of whom were ineligible. Another 18 patients declined participation, leaving 204 who completed the protocol.

Before testing began, we estimated the standard deviation of each aneroid sphygmomanometer and the assigned observer by repeatedly measuring the BP of a healthy normotensive individual sitting in the standard position. We obtained 46 measurements over 2 days to avoid subject and operator fatigue. Standard deviation for systolic BP was 3.6 mm Hg; for diastolic it was 3.8 mm Hg.

During testing, nurses recorded BP for each patient twice in the examination table position and twice in the standard position. They entered data into an Excel workbook for subsequent analysis. All examination rooms were equipped with newly purchased aneroid sphygmomanometers, and the appropriate cuff size was selected for each patient. Patients were instructed to remain quiet during the measurements. Patients sat first on the edge of the examination table. After a 5-minute rest, BP was measured twice in the same arm. Measurements were separated by 1 to 2 minutes. Patients then sat in the chair and rested another 2 minutes before BP was again measured twice in the same arm. The arms and back were supported in the chair and the stethoscope placed at heart level.

As per protocol, we obtained 4 BP readings on each patient and calculated the difference between the average systolic and diastolic BP values from the 2 positions. The standard error of the mean of this difference was determined using the equation, where Sd is the standard deviation of the aneroid sphygmomanometer and observer.¹² A one-sided, 95% confidence upper bound for the standard error of the difference is 1.65 × SEd. We compared patient-specific differences against this upper bound to identify significant systolic and diastolic BP changes due to positioning. If the patient’s BP difference exceeded the upper bound, it was attributed to the positional change and not to variation inherent to the sphygmomanometer and observer.

As an example, consider a patient whose average systolic BP readings from the examination-table and standard positions, respectively, were 128 mm Hg and 120 mm Hg. Assuming an SEd of 3.55 and an upper bound of 5.86, the observed 8 mm Hg difference in average systolic BPs would be considered significant. The amount of random variation from the sphygmomanometer and observer would not be expected to exceed 5.86 mm Hg.

In accordance with accepted standards, prehypertension was defined as a BP between 120-139/80-89 mm Hg, and hypertension was defined as a BP ≥140/90 mm Hg.⁴ BP below 120/80 mm Hg was considered normal. We calculated each patient’s average systolic and diastolic BP values in the 2 positions and thereby classified the individual as normotensive, prehypertensive, or hypertensive. We regarded as misclassified any patient whose BP showed significant lowering between the examination-table and standard positions resulting in a change of classification from prehypertensive or hypertensive to normotensive. For example, a patient with an examination-table position average reading of 126/85 mm Hg and a standard position average reading of 118/78 mm Hg would have been misclassified as prehypertensive.

We reviewed charts and gathered data, including subject age, sex, obesity (defined as a body mass index of ≥30 kg/m²), and history of diabetes, hypertension, or smoking. Other than age, all data were binary. We performed logistic regression analysis using the Excel Add-in Real Statistics Resource Pack software (Release 4.3)¹³ to determine if these factors could predict significant lowering of BP due to positional change.

Our associated observational study. We also conducted a separate observational study of 25 regional primary care offices to evaluate compliance with the AHA guidelines for measuring BP. The office nurses taking measurements were not informed of the study’s purpose to prevent deviation from their common practice.

In our study, 13.2% of patients classified as prehypertensive or hypertensive when they sat on the exam table were found to be normotensive when seated in the chair.

Data on 9 guideline criteria were collected to assess supervision of patients before and during measurements, including having the patient sit in a chair in quiet and comfortable surroundings with arms and back supported and feet on the ground. We also noted the type of BP measuring device used. Additionally, observers assessed the technique of the individuals using a manual device, including cuff placement and deflation rate. The observations were conducted during a clinic visit by a medical student knowledgeable in the AHA guidelines for measuring BP by automated oscillometric or aneroid sphygmomanometric devices. We conducted the study over a 2-week period in the second quarter of 2016.

RESULTS

Power analysis performed prior to the study showed that a minimum of 26 patients would be needed to predict a 2 mm Hg difference between BPs obtained in the 2 positions. Of the 204 patients used in the logistic regression analysis, 78 were men and 126 were women. Ages ranged from 18 to 101 years, yielding a mean of 54. One-hundred sixteen had previously received a diagnosis of hypertension, 39 had diabetes, 92 were obese, 22 were current smokers, and 68 were former smokers.

TABLE 1 shows the means and ranges of systolic and diastolic BP for both study positions. With this study population, mean BP recorded in the examination-table position decreased in the standard position by 2.1 and 2.2 mm Hg for systolic and diastolic BP, respectively (P<.001).

Significant BP lowering—as defined by a one-sided 95% confidence upper bound for the standard error of differences between study positions—was determined to be 5.86 and 6.22 mm Hg for systolic and diastolic pressures, respectively. Significant lowering of BP and misclassification due to positioning are summarized in TABLE 2. Significant lowering of mean systolic or diastolic BP with positional change from table to chair occurred in 62 subjects (30.4%). Misclassification of prehypertension occurred in 7.4% of subjects, and misclassification of hypertension occurred in 5.9%.

Logistic regression using patient age, sex, obesity, and history of diabetes, hypertension, and smoking as independent factors did not predict significant BP lowering with positional change.

Our observational study revealed that proper positioning in a chair was followed in only 10 of the 25 offices. In the remaining offices, patients were seated on the examination table. A 5-minute rest period before measuring BP was allowed in only 10 of the 25 offices. An automated oscillometric device was used in only 2 of the 25 offices.

DISCUSSION

In this study, 27 subjects (13.2%) were misclassified as prehypertensive or hypertensive as a result of deviating from the standard position in obtaining BP. Although the standard position is universally recommended, the guideline is not always followed in clinical practice.¹⁴

One study by Villegas et al found that 60% of physicians and nurses working in a major hospital were measuring BP inaccurately.¹⁵ In our initial observational study, 60% of primary care practices visited did not adhere to the recommended patient positioning. These medical offices are located in the community surrounding our facility and are operated by the same health care organization. The misclassification of prehypertension and hypertension observed in our prospective comparison of BP recordings in table and chair positions is, therefore, likely to occur to some degree at these practices, as well.

Similar diagnostic misclassifications have been reported in other medical settings. In a published survey of 114 medical offices, McKay and coworkers noted frequent inconsistencies with published guidelines in measuring BP.¹⁶

Common clinical demographic data obtained during this study showed no association with the positional BP change. Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of elevated BP for this subgroup of individuals. Measuring muscle tension of the arms and back while seated on an exam table and chair was beyond the scope of this study.

In clinical practice, different types of BP measuring devices are used. Calibration and quality control of these devices is often lacking.¹⁷ Before starting our study, we determined the statistical variance of the aneroid sphygmomanometers and found it to approximate the manufacturer’s precision specification. Guidelines recommend using the mean of 2 BP readings as representing the patient’s BP for a given clinic visit. Additional readings are recommended if there is more than a 5 mm Hg difference between the initial 2 readings.⁴

In our study, we used sampling statistics of the BP readings and clinical guideline BP ranges in making diagnostic determinations. The inability to identify those patients whose BP will be affected by positional change highlights the importance of following standard BP measurement guidelines for all patients.

Study limitations. Positional change in BP from examination table to chair lacks a comparison to BP changes in positioning from chair to table. If similar BP changes in the reverse sequence were to be observed, this would add support to the hypothesis that muscle tension of the unsupported body is a cause of BP elevation in certain individuals. We believe, however, that the sequence of BP measurements (from table to chair) did not have a significant impact because all patients were allowed to rest in each position before the BP was measured. The BP was therefore measured in a steady-state in both positions.

Increased muscle tension due to lack of body support while sitting on the edge of the examination table could be the cause of the elevated BP.

Additionally, BP measurement by aneroid sphygmomanometry is highly dependent on observer skill and hearing ability. Furthermore, a disproportionate number of BP measurements recorded in the study ended in zero, suggesting terminal digit bias by the observer. These sources of error may be avoided using an automated oscillometric measuring device.¹⁸ Automated devices also allow for repeated independent measurements that minimize the white-coat effect. However, there are also limitations to the accuracy of oscillometric equipment. This is especially true when recording BP in the elderly, a group whose stiff arterial walls may cause erroneous measurements.¹⁹

Guideline justification. Nonadherence to standard positioning when measuring BP leads to certain individuals being misclassified as prehypertensive or hypertensive. Misclassification in turn leads to unnecessary medical encounters, testing, and treatment. Misdiagnosis is also likely to increase the cost of an individual’s insurance coverage and out-of-pocket health care expenses.

CORRESPONDENCE
Roy N. Morcos, MD, St. Elizabeth Family Medicine Residency Program, 8423 Market Street, Suite 101, Boardman, Ohio 44512; [email protected].

Resources

1. US Preventive Services Task Force. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319:588-594.
2. Henderson JT, Webber EM, Sawaya GF. Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;319:595-606.

Resources

1. US Preventive Services Task Force. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319:588-594.
2. Henderson JT, Webber EM, Sawaya GF. Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;319:595-606.

Resources

1. US Preventive Services Task Force. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319:588-594.
2. Henderson JT, Webber EM, Sawaya GF. Screening for ovarian cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;319:595-606.

In his bimonthly podcast, Dr David Henry, the JCSO Editor-in-Chief, discusses the approval of the biosimilars, bevacizumab-awwb and trastuzumab-dkst, and new therapies for virally associated cancers. Also in the line-up are an interview with Dr Daniel Haller on the latest advances in treating gastrointestinal cancers, and an article on hands-on advice on integrating survivorship care planning in a radiation oncology workflow. Research topics incude how to improve communication between oncology care providers and patient caregivers during hospice; the impact of patient education on enrollment in clinical trials; and organizational barriers to optimal lung cancer care in the community setting. A series of Case Reports that highlight some of the clincial challenges in treating patients with cancer round out the issue.

Listen to the podcast below

In his bimonthly podcast, Dr David Henry, the JCSO Editor-in-Chief, discusses the approval of the biosimilars, bevacizumab-awwb and trastuzumab-dkst, and new therapies for virally associated cancers. Also in the line-up are an interview with Dr Daniel Haller on the latest advances in treating gastrointestinal cancers, and an article on hands-on advice on integrating survivorship care planning in a radiation oncology workflow. Research topics incude how to improve communication between oncology care providers and patient caregivers during hospice; the impact of patient education on enrollment in clinical trials; and organizational barriers to optimal lung cancer care in the community setting. A series of Case Reports that highlight some of the clincial challenges in treating patients with cancer round out the issue.

Listen to the podcast below

In his bimonthly podcast, Dr David Henry, the JCSO Editor-in-Chief, discusses the approval of the biosimilars, bevacizumab-awwb and trastuzumab-dkst, and new therapies for virally associated cancers. Also in the line-up are an interview with Dr Daniel Haller on the latest advances in treating gastrointestinal cancers, and an article on hands-on advice on integrating survivorship care planning in a radiation oncology workflow. Research topics incude how to improve communication between oncology care providers and patient caregivers during hospice; the impact of patient education on enrollment in clinical trials; and organizational barriers to optimal lung cancer care in the community setting. A series of Case Reports that highlight some of the clincial challenges in treating patients with cancer round out the issue.

Listen to the podcast below

Click here to read the supplement

CME: Opioid Use Disorder: Challenges and Solutions to a Rising Epidemic

Earn 1.25 CME Credits.

• Introduction and 2 Case Studies by Genie L. Bailey, MD
• Opioid Use Disorder: The Epidemic is Real by Kevin P. Hill, MD, MHS
• Managing the Opioid Use Disorder Crisis by Richard N. Rosenthal, MD

Click here to read the supplement

Click here to read the supplement

CME: Opioid Use Disorder: Challenges and Solutions to a Rising Epidemic

Earn 1.25 CME Credits.

• Introduction and 2 Case Studies by Genie L. Bailey, MD
• Opioid Use Disorder: The Epidemic is Real by Kevin P. Hill, MD, MHS
• Managing the Opioid Use Disorder Crisis by Richard N. Rosenthal, MD

Click here to read the supplement

Click here to read the supplement

CME: Opioid Use Disorder: Challenges and Solutions to a Rising Epidemic

Earn 1.25 CME Credits.

• Introduction and 2 Case Studies by Genie L. Bailey, MD
• Opioid Use Disorder: The Epidemic is Real by Kevin P. Hill, MD, MHS
• Managing the Opioid Use Disorder Crisis by Richard N. Rosenthal, MD

Click here to read the supplement

Q2. Correct Answer: C 
 
Rationale  
The patient presents with acute gallstone pancreatitis. In patients with gallstone pancreatitis and evidence of cholangitis, ERCP with sphincterotomy and stone extraction should be performed. The patients fever, jaundice, and right upper quadrant pain are sufficient to make the diagnosis of cholangitis. It is too early in the course of the disease to evaluate for pancreatic necrosis. Typically, triglyceride levels above 1,000 mg/dL are required to induce pancreatitis. Finally, while the patient has cholelithiasis, there is no evidence of cholecystitis. Therefore, a HIDA scan is not warranted. 
 
Reference  
1. Behrns KE, Ashley SW, Hunter JG, Carr-Locke D. Early ERCP for gallstone pancreatitis: for whom and when? J Gastrointestinal Surgery. 2008;12(4):629-33. 
 

Q2. Correct Answer: C 
 
Rationale  
The patient presents with acute gallstone pancreatitis. In patients with gallstone pancreatitis and evidence of cholangitis, ERCP with sphincterotomy and stone extraction should be performed. The patients fever, jaundice, and right upper quadrant pain are sufficient to make the diagnosis of cholangitis. It is too early in the course of the disease to evaluate for pancreatic necrosis. Typically, triglyceride levels above 1,000 mg/dL are required to induce pancreatitis. Finally, while the patient has cholelithiasis, there is no evidence of cholecystitis. Therefore, a HIDA scan is not warranted. 
 
Reference  
1. Behrns KE, Ashley SW, Hunter JG, Carr-Locke D. Early ERCP for gallstone pancreatitis: for whom and when? J Gastrointestinal Surgery. 2008;12(4):629-33. 
 

Q2. Correct Answer: C 
 
Rationale  
The patient presents with acute gallstone pancreatitis. In patients with gallstone pancreatitis and evidence of cholangitis, ERCP with sphincterotomy and stone extraction should be performed. The patients fever, jaundice, and right upper quadrant pain are sufficient to make the diagnosis of cholangitis. It is too early in the course of the disease to evaluate for pancreatic necrosis. Typically, triglyceride levels above 1,000 mg/dL are required to induce pancreatitis. Finally, while the patient has cholelithiasis, there is no evidence of cholecystitis. Therefore, a HIDA scan is not warranted. 
 
Reference  
1. Behrns KE, Ashley SW, Hunter JG, Carr-Locke D. Early ERCP for gallstone pancreatitis: for whom and when? J Gastrointestinal Surgery. 2008;12(4):629-33. 
 

Q1. Correct Answer: C 
 
Rationale  
The CagA strain of H. pylori has been found to be associated with an increased risk of gastric adenocarcinoma and MALT lymphoma. CagA-producing H. pylori infection also cause more severe mucosal inflammation and is associated with higher incidences of gastric and duodenal ulcers. A protective effect of CagA+ H. pylori against gastroesophageal reflux disease, reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma has been suggested, as some epidemiologic studies have shown a decreased prevalence of these disorders. Although further studies are needed to verify these relationships, no studies to date have demonstrated an increased risk of esophageal carcinoma associated with H. pylori. CagA-producing H. pylori has not been associated with gastric carcinoid tumor. 
 
References  
1. Fallone CA, Barkun AN, Göttke MU, et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol. 2000;95(3):659-69. 
2. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003;125(6):1636-44. 
3. Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res. 2008;1:329-38. 

Q1. Correct Answer: C 
 
Rationale  
The CagA strain of H. pylori has been found to be associated with an increased risk of gastric adenocarcinoma and MALT lymphoma. CagA-producing H. pylori infection also cause more severe mucosal inflammation and is associated with higher incidences of gastric and duodenal ulcers. A protective effect of CagA+ H. pylori against gastroesophageal reflux disease, reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma has been suggested, as some epidemiologic studies have shown a decreased prevalence of these disorders. Although further studies are needed to verify these relationships, no studies to date have demonstrated an increased risk of esophageal carcinoma associated with H. pylori. CagA-producing H. pylori has not been associated with gastric carcinoid tumor. 
 
References  
1. Fallone CA, Barkun AN, Göttke MU, et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol. 2000;95(3):659-69. 
2. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003;125(6):1636-44. 
3. Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res. 2008;1:329-38. 

Q1. Correct Answer: C 
 
Rationale  
The CagA strain of H. pylori has been found to be associated with an increased risk of gastric adenocarcinoma and MALT lymphoma. CagA-producing H. pylori infection also cause more severe mucosal inflammation and is associated with higher incidences of gastric and duodenal ulcers. A protective effect of CagA+ H. pylori against gastroesophageal reflux disease, reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma has been suggested, as some epidemiologic studies have shown a decreased prevalence of these disorders. Although further studies are needed to verify these relationships, no studies to date have demonstrated an increased risk of esophageal carcinoma associated with H. pylori. CagA-producing H. pylori has not been associated with gastric carcinoid tumor. 
 
References  
1. Fallone CA, Barkun AN, Göttke MU, et al. Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases. Am J Gastroenterol. 2000;95(3):659-69. 
2. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 2003;125(6):1636-44. 
3. Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res. 2008;1:329-38. 

Most skin-aging treatments work by prodding old fibroblasts and keratinocytes to accelerate the production of important cellular components. For example, retinoids act on retinoic acid receptors to activate collagen genes and deactivate collagenase genes. Glycolic acid, ascorbic acid, and certain growth factors stimulate synthesis of collagen by fibroblasts. Older fibroblasts and keratinocytes are sluggish for many reasons; they do not “hear” signals as well as younger cells do. Glycosaminoglycans such as heparan sulfate can help cells hear these signals. Heparan sulfate, for example, assists in the delivery of growth factors to cells, stabilizes them, and presents them to the receptors on the keratinocytes and fibroblasts, and amplifies cellular response to these factors.

A new angle in antiaging skin care is to create new keratinocytes rather than to stimulate old cells. For the last decade, personal care companies have touted the benefit of putting stem cells in cosmeceuticals, claiming that these cells would rejuvenate skin. However, this proved to be unsubstantiated marketing hype because the stem cells were plant derived (often from apples), had poor shelf life, and could not intercalate between the native skin cells and work with them to have any effect. Stems cells in cosmeceuticals became a point of disdain for savvy scientists.

Stem cells

Wounding the skin stimulates LGR6+ stem cells. This occurs when neutrophils in the immune system release defensins in response to injury, and, in turn, defensins activate LGR6+ stem cells. Situated above the follicular bulge, these cells are reported to have the capacity to synthesize all cutaneous cell lineages, including sebaceous gland and interfollicular epidermal cells.^1,2 There are no specific studies that show that the LGR6+ cells generate new fibroblasts, but it seems likely. Transplantation of LGR6+ stem cells into the skin results in increased wound healing, hair follicle genesis, and angiogenesis.³ LGR6+ stem cells repopulate the epidermis by creating new basal stem cells. In regards to skin rejuvenation, it is clear that activated LGR6+ stems cells produce new, younger-acting keratinocytes in the epidermis.

Peptides

Defensin is a peptide. Peptides are short amino acid chains. These important substances are challenging to incorporate into topical formulations for various reasons, including stabilization difficulty, interaction with other molecules, and poor penetration (greater than 500 Dalton molecular weight). For these reasons, many peptide-containing formulations do not have efficacy. Attempts are underway to better develop or modify peptide products to enhance solubility, achieve better penetration, and target increased receptor activity. Defensins are peptides, which makes them difficult to formulate in a topical product. Special steps must be taken in the formulation process to stabilize defensin and allow penetration into the hair follicle where the LGR6+ cells reside. Fortunately, it is easier for a peptide to target the hair follicle because it can traverse through the “pore” – than it is to get a peptide to reach the fibroblasts in the dermis.

Defensins

Defensins, or human beta-defensins, are host defense peptides that exhibit antimicrobial activities against numerous bacteria.⁴ LGR6+ stem cells, which are dormant until they are activated to respond to damage, are stimulated by defensins. Defensins have been shown to stimulate keratinocyte proliferation, migration, and wound healing. (3) **Human alpha-defensin 5 peptide has also been shown to enhance wound healing, increasing LGR5+ and LGR6+ stem cell migration in the wound bed.(1)***

When formulated in a manner that allows for stability and penetration into the hair follicle where the LGR6+ stem cells reside, defensin formulations can be applied topically. A product sold as DefenAge uses a patented formulation that uses albumin, a large and stable protein, to stabilize defensin and act as a carrier molecule while helping the defensin maintain its integrity and extend shelf life in the serum base. The albumin/defensin complex is incorporated into liposomes to prevent other ingredients in the cosmetic base from interacting with the peptide and to enhance delivery to the LGR6+ target cell.
 

The role of defensins in treating skin aging

• Old fibroblast and keratinocytes are sluggish and lazy.
• Old cells do not “hear” signals as well as younger cells.
• LGR6+ stem cells repopulate the epidermis with new, young keratinocytes.
• Defensin stimulates LGR6+ stem cells.
• The defensin/LGR6+ pathway plays a role in keratinization.
• Using topical defensin can improve the skin’s appearance.

Studying DefenAge

At this time, there is only one small multicenter, double-blind, placebo-controlled clinical study completed at three locations by investigators who are stockholders in the company and an independent dermatologic histopathologist who has no relation with the company; results have been reported in aesthetic dermatology industry newsletters. Each site had 15 patients for a total of 45 patients; all were women, aged 41-70 years (average age, 60 years), with little or no history of “quality” skin care. The study regimen used a system that contained alpha- and beta-defensins developed by Progenitor Biologics. Thirty patients used the three products in the DefenAge line: the 2-Minute Reveal Masque Exfoliator, 24/7 Barrier Balance Cream, and 8-in-1 BioSerum. The remaining patients received a three-part placebo system. Baseline biopsies were obtained to evaluate underlying conditions in the patients’ skin, and their skin was evaluated at 6 and 12 weeks, when additional biopsies were taken. Data analysis indicated that patients using DefenAge experienced significant improvement in coarse and fine wrinkles, pigmentation, pore prominence, epidermal thickness, as well as skin texture and evenness.

My personal opinion

I have never been a fan of formulations containing stem cells or peptides for the reasons listed above. DefenAge is unique in the way it has been stabilized, by penetrating the hair follicle rather than through the dermis and because defensin has very well-documented effects on the important LGR6+ stem cells. The effects of defensin on LGR6+ stem cells intrigue me. I do not intend to stop recommending retinoids for antiaging, but rather will add DefenAge to the antiaging regimen. In the past year, I have used DefenAge on many patients and have had many observations. I do not recommend starting retinoids and DefenAge at the same time because I have seen increased retinoid dermatitis. I suggest starting one the first month and then introducing the other product during the second month. Although no studies have been performed on this, my impression is that the DefenAge gives a quick result that helps improve patient compliance with the entire skin care regimen, but the effects reach a point at which no further improvement is seen. Combining DefenAge with a skin care regimen (targeted specifically to their Baumann Skin Type of course!) that includes a retinoid will increase efficacy. For wrinkle-prone skin types, I combine DefenAge with a retinoid, vitamin C, and heparan sulfate. After cleansing in the morning, I have them apply vitamin C followed by the DefenAge and an SPF. In the evening after cleansing, I have them apply a retinoid followed by a heparan sulfate analogue.

Conclusion

DefenAge offers a new approach to skin aging. At this time, there is much basic science research about the benefits of LGR6+ and that uses defensin to stimulate these stem cells; however, only one small clinical trial using defensin topically for antiaging has been published. It is doubtful that many studies will be performed because cosmetic companies are not allowed to make biologic claims so they have little incentive to demonstrate biologic changes. For this reason, we have to rely upon anecdotal reports from physicians such as the information that I have shared here.

Conflict of interest note: I have no financial relationship (no honorarium, stocks, or research funding) with Progenitor Biologics. I was asked to lecture in a DefenAge Symposium at the Vegas Cosmetic Surgery meeting but received no compensation. DefenAge products are sold through doctors, with my company, Skin Type Solutions Franchise Systems, as are heparan sulfate analogues, multiple brands of retinol, and 40 other product brands.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also authored a New York Times Best Seller for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance Therapeutics. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Lough D et al. Plast Reconstr Surg. 2013 Nov;132(5):1159-71.

2. Snippert HJ et al. Science. 2010 Mar 12;327(5971):1385-9.

3. Lough DM et al. Plast Reconstr Surg. 2014 Mar;133(3):579-90.

4. Kiatsurayanon C et al. J Invest Dermatol. 2014 Aug;134(8):2163-73.
 

Most skin-aging treatments work by prodding old fibroblasts and keratinocytes to accelerate the production of important cellular components. For example, retinoids act on retinoic acid receptors to activate collagen genes and deactivate collagenase genes. Glycolic acid, ascorbic acid, and certain growth factors stimulate synthesis of collagen by fibroblasts. Older fibroblasts and keratinocytes are sluggish for many reasons; they do not “hear” signals as well as younger cells do. Glycosaminoglycans such as heparan sulfate can help cells hear these signals. Heparan sulfate, for example, assists in the delivery of growth factors to cells, stabilizes them, and presents them to the receptors on the keratinocytes and fibroblasts, and amplifies cellular response to these factors.

A new angle in antiaging skin care is to create new keratinocytes rather than to stimulate old cells. For the last decade, personal care companies have touted the benefit of putting stem cells in cosmeceuticals, claiming that these cells would rejuvenate skin. However, this proved to be unsubstantiated marketing hype because the stem cells were plant derived (often from apples), had poor shelf life, and could not intercalate between the native skin cells and work with them to have any effect. Stems cells in cosmeceuticals became a point of disdain for savvy scientists.

Stem cells

Wounding the skin stimulates LGR6+ stem cells. This occurs when neutrophils in the immune system release defensins in response to injury, and, in turn, defensins activate LGR6+ stem cells. Situated above the follicular bulge, these cells are reported to have the capacity to synthesize all cutaneous cell lineages, including sebaceous gland and interfollicular epidermal cells.^1,2 There are no specific studies that show that the LGR6+ cells generate new fibroblasts, but it seems likely. Transplantation of LGR6+ stem cells into the skin results in increased wound healing, hair follicle genesis, and angiogenesis.³ LGR6+ stem cells repopulate the epidermis by creating new basal stem cells. In regards to skin rejuvenation, it is clear that activated LGR6+ stems cells produce new, younger-acting keratinocytes in the epidermis.

Peptides

Defensin is a peptide. Peptides are short amino acid chains. These important substances are challenging to incorporate into topical formulations for various reasons, including stabilization difficulty, interaction with other molecules, and poor penetration (greater than 500 Dalton molecular weight). For these reasons, many peptide-containing formulations do not have efficacy. Attempts are underway to better develop or modify peptide products to enhance solubility, achieve better penetration, and target increased receptor activity. Defensins are peptides, which makes them difficult to formulate in a topical product. Special steps must be taken in the formulation process to stabilize defensin and allow penetration into the hair follicle where the LGR6+ cells reside. Fortunately, it is easier for a peptide to target the hair follicle because it can traverse through the “pore” – than it is to get a peptide to reach the fibroblasts in the dermis.

Defensins

Defensins, or human beta-defensins, are host defense peptides that exhibit antimicrobial activities against numerous bacteria.⁴ LGR6+ stem cells, which are dormant until they are activated to respond to damage, are stimulated by defensins. Defensins have been shown to stimulate keratinocyte proliferation, migration, and wound healing. (3) **Human alpha-defensin 5 peptide has also been shown to enhance wound healing, increasing LGR5+ and LGR6+ stem cell migration in the wound bed.(1)***

When formulated in a manner that allows for stability and penetration into the hair follicle where the LGR6+ stem cells reside, defensin formulations can be applied topically. A product sold as DefenAge uses a patented formulation that uses albumin, a large and stable protein, to stabilize defensin and act as a carrier molecule while helping the defensin maintain its integrity and extend shelf life in the serum base. The albumin/defensin complex is incorporated into liposomes to prevent other ingredients in the cosmetic base from interacting with the peptide and to enhance delivery to the LGR6+ target cell.
 

The role of defensins in treating skin aging

• Old fibroblast and keratinocytes are sluggish and lazy.
• Old cells do not “hear” signals as well as younger cells.
• LGR6+ stem cells repopulate the epidermis with new, young keratinocytes.
• Defensin stimulates LGR6+ stem cells.
• The defensin/LGR6+ pathway plays a role in keratinization.
• Using topical defensin can improve the skin’s appearance.

Studying DefenAge

At this time, there is only one small multicenter, double-blind, placebo-controlled clinical study completed at three locations by investigators who are stockholders in the company and an independent dermatologic histopathologist who has no relation with the company; results have been reported in aesthetic dermatology industry newsletters. Each site had 15 patients for a total of 45 patients; all were women, aged 41-70 years (average age, 60 years), with little or no history of “quality” skin care. The study regimen used a system that contained alpha- and beta-defensins developed by Progenitor Biologics. Thirty patients used the three products in the DefenAge line: the 2-Minute Reveal Masque Exfoliator, 24/7 Barrier Balance Cream, and 8-in-1 BioSerum. The remaining patients received a three-part placebo system. Baseline biopsies were obtained to evaluate underlying conditions in the patients’ skin, and their skin was evaluated at 6 and 12 weeks, when additional biopsies were taken. Data analysis indicated that patients using DefenAge experienced significant improvement in coarse and fine wrinkles, pigmentation, pore prominence, epidermal thickness, as well as skin texture and evenness.

My personal opinion

I have never been a fan of formulations containing stem cells or peptides for the reasons listed above. DefenAge is unique in the way it has been stabilized, by penetrating the hair follicle rather than through the dermis and because defensin has very well-documented effects on the important LGR6+ stem cells. The effects of defensin on LGR6+ stem cells intrigue me. I do not intend to stop recommending retinoids for antiaging, but rather will add DefenAge to the antiaging regimen. In the past year, I have used DefenAge on many patients and have had many observations. I do not recommend starting retinoids and DefenAge at the same time because I have seen increased retinoid dermatitis. I suggest starting one the first month and then introducing the other product during the second month. Although no studies have been performed on this, my impression is that the DefenAge gives a quick result that helps improve patient compliance with the entire skin care regimen, but the effects reach a point at which no further improvement is seen. Combining DefenAge with a skin care regimen (targeted specifically to their Baumann Skin Type of course!) that includes a retinoid will increase efficacy. For wrinkle-prone skin types, I combine DefenAge with a retinoid, vitamin C, and heparan sulfate. After cleansing in the morning, I have them apply vitamin C followed by the DefenAge and an SPF. In the evening after cleansing, I have them apply a retinoid followed by a heparan sulfate analogue.

Conclusion

DefenAge offers a new approach to skin aging. At this time, there is much basic science research about the benefits of LGR6+ and that uses defensin to stimulate these stem cells; however, only one small clinical trial using defensin topically for antiaging has been published. It is doubtful that many studies will be performed because cosmetic companies are not allowed to make biologic claims so they have little incentive to demonstrate biologic changes. For this reason, we have to rely upon anecdotal reports from physicians such as the information that I have shared here.

Conflict of interest note: I have no financial relationship (no honorarium, stocks, or research funding) with Progenitor Biologics. I was asked to lecture in a DefenAge Symposium at the Vegas Cosmetic Surgery meeting but received no compensation. DefenAge products are sold through doctors, with my company, Skin Type Solutions Franchise Systems, as are heparan sulfate analogues, multiple brands of retinol, and 40 other product brands.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also authored a New York Times Best Seller for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance Therapeutics. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Lough D et al. Plast Reconstr Surg. 2013 Nov;132(5):1159-71.

2. Snippert HJ et al. Science. 2010 Mar 12;327(5971):1385-9.

3. Lough DM et al. Plast Reconstr Surg. 2014 Mar;133(3):579-90.

4. Kiatsurayanon C et al. J Invest Dermatol. 2014 Aug;134(8):2163-73.
 

Most skin-aging treatments work by prodding old fibroblasts and keratinocytes to accelerate the production of important cellular components. For example, retinoids act on retinoic acid receptors to activate collagen genes and deactivate collagenase genes. Glycolic acid, ascorbic acid, and certain growth factors stimulate synthesis of collagen by fibroblasts. Older fibroblasts and keratinocytes are sluggish for many reasons; they do not “hear” signals as well as younger cells do. Glycosaminoglycans such as heparan sulfate can help cells hear these signals. Heparan sulfate, for example, assists in the delivery of growth factors to cells, stabilizes them, and presents them to the receptors on the keratinocytes and fibroblasts, and amplifies cellular response to these factors.

A new angle in antiaging skin care is to create new keratinocytes rather than to stimulate old cells. For the last decade, personal care companies have touted the benefit of putting stem cells in cosmeceuticals, claiming that these cells would rejuvenate skin. However, this proved to be unsubstantiated marketing hype because the stem cells were plant derived (often from apples), had poor shelf life, and could not intercalate between the native skin cells and work with them to have any effect. Stems cells in cosmeceuticals became a point of disdain for savvy scientists.

Stem cells

Wounding the skin stimulates LGR6+ stem cells. This occurs when neutrophils in the immune system release defensins in response to injury, and, in turn, defensins activate LGR6+ stem cells. Situated above the follicular bulge, these cells are reported to have the capacity to synthesize all cutaneous cell lineages, including sebaceous gland and interfollicular epidermal cells.^1,2 There are no specific studies that show that the LGR6+ cells generate new fibroblasts, but it seems likely. Transplantation of LGR6+ stem cells into the skin results in increased wound healing, hair follicle genesis, and angiogenesis.³ LGR6+ stem cells repopulate the epidermis by creating new basal stem cells. In regards to skin rejuvenation, it is clear that activated LGR6+ stems cells produce new, younger-acting keratinocytes in the epidermis.

Peptides

Defensin is a peptide. Peptides are short amino acid chains. These important substances are challenging to incorporate into topical formulations for various reasons, including stabilization difficulty, interaction with other molecules, and poor penetration (greater than 500 Dalton molecular weight). For these reasons, many peptide-containing formulations do not have efficacy. Attempts are underway to better develop or modify peptide products to enhance solubility, achieve better penetration, and target increased receptor activity. Defensins are peptides, which makes them difficult to formulate in a topical product. Special steps must be taken in the formulation process to stabilize defensin and allow penetration into the hair follicle where the LGR6+ cells reside. Fortunately, it is easier for a peptide to target the hair follicle because it can traverse through the “pore” – than it is to get a peptide to reach the fibroblasts in the dermis.

Defensins

Defensins, or human beta-defensins, are host defense peptides that exhibit antimicrobial activities against numerous bacteria.⁴ LGR6+ stem cells, which are dormant until they are activated to respond to damage, are stimulated by defensins. Defensins have been shown to stimulate keratinocyte proliferation, migration, and wound healing. (3) **Human alpha-defensin 5 peptide has also been shown to enhance wound healing, increasing LGR5+ and LGR6+ stem cell migration in the wound bed.(1)***

When formulated in a manner that allows for stability and penetration into the hair follicle where the LGR6+ stem cells reside, defensin formulations can be applied topically. A product sold as DefenAge uses a patented formulation that uses albumin, a large and stable protein, to stabilize defensin and act as a carrier molecule while helping the defensin maintain its integrity and extend shelf life in the serum base. The albumin/defensin complex is incorporated into liposomes to prevent other ingredients in the cosmetic base from interacting with the peptide and to enhance delivery to the LGR6+ target cell.
 

The role of defensins in treating skin aging

• Old fibroblast and keratinocytes are sluggish and lazy.
• Old cells do not “hear” signals as well as younger cells.
• LGR6+ stem cells repopulate the epidermis with new, young keratinocytes.
• Defensin stimulates LGR6+ stem cells.
• The defensin/LGR6+ pathway plays a role in keratinization.
• Using topical defensin can improve the skin’s appearance.

Studying DefenAge

At this time, there is only one small multicenter, double-blind, placebo-controlled clinical study completed at three locations by investigators who are stockholders in the company and an independent dermatologic histopathologist who has no relation with the company; results have been reported in aesthetic dermatology industry newsletters. Each site had 15 patients for a total of 45 patients; all were women, aged 41-70 years (average age, 60 years), with little or no history of “quality” skin care. The study regimen used a system that contained alpha- and beta-defensins developed by Progenitor Biologics. Thirty patients used the three products in the DefenAge line: the 2-Minute Reveal Masque Exfoliator, 24/7 Barrier Balance Cream, and 8-in-1 BioSerum. The remaining patients received a three-part placebo system. Baseline biopsies were obtained to evaluate underlying conditions in the patients’ skin, and their skin was evaluated at 6 and 12 weeks, when additional biopsies were taken. Data analysis indicated that patients using DefenAge experienced significant improvement in coarse and fine wrinkles, pigmentation, pore prominence, epidermal thickness, as well as skin texture and evenness.

My personal opinion

I have never been a fan of formulations containing stem cells or peptides for the reasons listed above. DefenAge is unique in the way it has been stabilized, by penetrating the hair follicle rather than through the dermis and because defensin has very well-documented effects on the important LGR6+ stem cells. The effects of defensin on LGR6+ stem cells intrigue me. I do not intend to stop recommending retinoids for antiaging, but rather will add DefenAge to the antiaging regimen. In the past year, I have used DefenAge on many patients and have had many observations. I do not recommend starting retinoids and DefenAge at the same time because I have seen increased retinoid dermatitis. I suggest starting one the first month and then introducing the other product during the second month. Although no studies have been performed on this, my impression is that the DefenAge gives a quick result that helps improve patient compliance with the entire skin care regimen, but the effects reach a point at which no further improvement is seen. Combining DefenAge with a skin care regimen (targeted specifically to their Baumann Skin Type of course!) that includes a retinoid will increase efficacy. For wrinkle-prone skin types, I combine DefenAge with a retinoid, vitamin C, and heparan sulfate. After cleansing in the morning, I have them apply vitamin C followed by the DefenAge and an SPF. In the evening after cleansing, I have them apply a retinoid followed by a heparan sulfate analogue.

Conclusion

DefenAge offers a new approach to skin aging. At this time, there is much basic science research about the benefits of LGR6+ and that uses defensin to stimulate these stem cells; however, only one small clinical trial using defensin topically for antiaging has been published. It is doubtful that many studies will be performed because cosmetic companies are not allowed to make biologic claims so they have little incentive to demonstrate biologic changes. For this reason, we have to rely upon anecdotal reports from physicians such as the information that I have shared here.

Conflict of interest note: I have no financial relationship (no honorarium, stocks, or research funding) with Progenitor Biologics. I was asked to lecture in a DefenAge Symposium at the Vegas Cosmetic Surgery meeting but received no compensation. DefenAge products are sold through doctors, with my company, Skin Type Solutions Franchise Systems, as are heparan sulfate analogues, multiple brands of retinol, and 40 other product brands.
 

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also authored a New York Times Best Seller for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance Therapeutics. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Lough D et al. Plast Reconstr Surg. 2013 Nov;132(5):1159-71.

2. Snippert HJ et al. Science. 2010 Mar 12;327(5971):1385-9.

3. Lough DM et al. Plast Reconstr Surg. 2014 Mar;133(3):579-90.

4. Kiatsurayanon C et al. J Invest Dermatol. 2014 Aug;134(8):2163-73.
 

Click here to access the April 2018 Digital Edition.

Table of Contents

• Understanding, Assessing, and Conceptualizing Suicide Risk Among Veterans With PTSD
• Reducing the Expenditures and Workload Associated With VA Partial-Fill Prescription Processing
• Acute Exertional Upper-Extremity Rhabdomyolysis in 3 Female Trainees
• A Practical Guide to Urine Drug Monitoring
• Synovial Chondromatosis: An Unusual Case of Knee Pain and Swelling
• Complementary and Integrative Health Therapies for Opioid Overuse

Click here to access the April 2018 Digital Edition.

Table of Contents

• Understanding, Assessing, and Conceptualizing Suicide Risk Among Veterans With PTSD
• Reducing the Expenditures and Workload Associated With VA Partial-Fill Prescription Processing
• Acute Exertional Upper-Extremity Rhabdomyolysis in 3 Female Trainees
• A Practical Guide to Urine Drug Monitoring
• Synovial Chondromatosis: An Unusual Case of Knee Pain and Swelling
• Complementary and Integrative Health Therapies for Opioid Overuse

Click here to access the April 2018 Digital Edition.

Table of Contents

• Understanding, Assessing, and Conceptualizing Suicide Risk Among Veterans With PTSD
• Reducing the Expenditures and Workload Associated With VA Partial-Fill Prescription Processing
• Acute Exertional Upper-Extremity Rhabdomyolysis in 3 Female Trainees
• A Practical Guide to Urine Drug Monitoring
• Synovial Chondromatosis: An Unusual Case of Knee Pain and Swelling
• Complementary and Integrative Health Therapies for Opioid Overuse