Clinical Review

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.

BY JEFF BAUER

A large retrospective analysis found a wide variation in opioid prescribing among emergency physicians (EPs) working within the same ED. The study also found that Medicare patients treated by EPs who wrote the most prescriptions for opioids were more likely to use opioids for 6 months after their ED visit than were those treated by EPs who wrote fewer opioid prescriptions.

Researchers evaluated initial visits to an ED by approximately 378,000 Medicare beneficiaries (average age: 68 years) from 2008 through 2011. None of these patients had received a prescription for an opioid in the 6 months before the ED visit, and none of the visits resulted in a hospital admission. Prescriptions for opioids (excluding methadone) were identified by the national drug code in the Medicare Part D database. An opioid prescription was attributed to the treating EP if the patient filled the prescription within 3 days after the ED visit.

Investigators categorized the treating EPs in this study as “high-intensity” or “low-intensity” opioid prescribers by calculating the proportion of all ED visits that resulted in an opioid prescription being filled. They then grouped the EPs into quartiles of opioid prescribing within each hospital. High-intensity prescribers were those in the top quartile of opioid prescribing rates, and low-intensity prescribers were those in the bottom quartile.

The primary outcome was long-term opioid use, defined as 6 months or more of opioids supplied in the 12 months after the initial ED visit. This did not include prescriptions filled within 30 days of the initial visit.

Overall, approximately 215,700 patients were treated by low-intensity prescribers and 162,000 by high-intensity prescribers. In general, the patient characteristics and diagnoses were similar in both groups. The rate of opioid prescribing of high-intensity prescribers was approximately triple the rate of low-intensity prescribers. High-intensity prescribers provided an opioid prescription for 21.4% of ED visits, compared to 7.3% among low-intensity prescribers.

Long-term opioid use at 12 months was significantly higher among patients who had been initially treated by high-intensity prescribers compared to those who had been treated by low-intensity prescribers (1.51% vs 1.16%; unadjusted odds ratio [OR], 1.31). There was minimal change in this difference after the results were adjusted for the patients’ age, race, sex, disability status, and presence of chronic conditions (OR, 1.30). The number needed to harm was calculated as 49, meaning theoretically, for every 49 patients who received a new opioid prescription in the ED, one would become a long-term user. The authors noted, however, that “…prescriptions provided by other physicians in the months after an [ED] visit are necessary for long-term opioid use to take hold.”

Researchers pointed out several limitations to their study. Because the study was observational, it could not establish causality. Researchers were not able to directly attribute opioid prescriptions to the treating EPs, but instead used prescriptions filled within 3 days of an ED visits as a surrogate; some opioid prescriptions could have been written by another clinician, such as the patient’s primary care physician during a follow-up visit. Because the study focused on Medicare patients, the results may not be applicable to younger patients. Based on their analysis, researchers could not determine whether an opioid prescription was appropriate, and therefore they could not quantify the extent of opioid overprescribing.

For more on EPs and opioid prescribing, see “The New Opioid Epidemic and the Law of Unintended Consequences” by Emergency Medicine Editor in Chief Neal Flomenbaum, MD (Emergency Medicine. 2017;49[2]:52) and “The New Opioid Epidemic: Prescriptions, Synthetics, and Street Drugs” by Rama B. Rao, MD and Emergency Medicine Associate Editor, Toxicology Lewis S. Nelson, MD (Emergency Medicine. 2017;49[2]:64-70).

Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med. 2017;376(7):663-673. doi:10.1056/NEJMsa1610524.

Lower Admission Rates, Other Factors Tied to High Rate of Death Soon After ED Discharge Among Older Adults

BY JEFF BAUER

Each year, approximately 10,000 older adult patients die within 7 days of discharge from an ED in the United States, despite having no obvious life-threatening illness, according to a large retrospective study. Emergency departments with lower rates of inpatient admission from the ED, lower patient volumes, and lower charges had significantly higher rates of death after discharge.

Researchers evaluated Medicare claims data related to slightly more than 10 million ED visits from 2007 to 2012. Because the goal was to study generally healthy patients, the following patients were excluded: individuals who were age 90 years and older; were receiving palliative or hospice care; or had received a life-limiting diagnosis, such as a myocardial infarction (MI) or a malignancy, either in the ED or in the year prior to the ED visit. The primary outcome was death within 7 days after discharge from an ED. The cause of death was determined by linking claims to death certificates; this information was available only for a subset of patients who visited an ED in 2007 or 2008.

Overall, during the 6-year study, 0.12% of discharged patients died within 7 days of discharge; this translates to more than 10,000 early deaths per year nationally. The leading causes of death were atherosclerotic heart disease (13.6%), MI (10.3%), and chronic obstructive pulmonary disease (9.6%).

Emergency departments ranked in the lowest fifth for admission rates admitted 15% of patients, compared to 56% of patients at EDs with the highest admission rates. The early death rate of patients treated at EDs with the lowest rates of inpatient admissions from the ED was 3.4 times higher than the death rate seen in EDs with the highest inpatient admission rates (0.27% vs 0.08%, respectively). This was true despite the fact that EDs with low-admission rates treated healthier patients, as evidenced by the overall 7-day mortality rate of all patients treated in the ED, whether they were admitted or discharged. Emergency departments that saw higher volumes of patients and had higher charges for visits had significantly fewer deaths.

Obermeyer Z, Cohn B, Wilson M, Jena AB, Cutler DM. Early death after discharge from emergency departments: analysis of national US insurance claims data. BMJ. 2017;356:j239. doi:10.1136/bmj.j239.

Tertiary Center Repeat Computed Tomography Scans Find Additional Injuries

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Imaging obtained at nontertiary trauma centers (NTCs) probably does not tell the whole story of a trauma patient’s injuries, according to a new retrospective study.

Repeat scans done at a Level 1 trauma center identified new injuries in 76% of patients who were transferred, Morgan Bonds, MD, reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma. About half of these previously unobserved injuries were considered clinically significant, said Dr Bonds, a surgical resident at the University of Oklahoma, Oklahoma City.

Her study examined imaging and clinical assessment of 203 trauma patients who were initially worked up at an NTC, and then transferred to the Level 1 University of Oklahoma tertiary trauma center (TTC). The facility’s primary radiologist reviewed all of the initial computed tomography (CT) scans while blinded to the NTC interpretation. The initial scans and interpretations were then compared with those done at the TTC.

The team split imaging and interpretation disconnects into four categories:

• Type A errors: A missed injury on the NTC scan. “This represents the expertise and experience of our primary radiologist,” Dr Bonds said.
• Type B errors: Missed injuries on scans where NTC radiologists saw other injuries that the TTC radiologist did not confirm. “This represents the experience of our radiologist and also the inexperience and overreaction of the NTC radiologists.”
• Type C errors: New injuries seen on additional TTC imaging of the same body area. “This represents the quality of the image.”
• Type D errors: New injuries found upon any new imaging, whether of a previously scanned or newly scanned body area. “This represents quality of work-up—the decision of the trauma team to more fully investigate the patient’s injuries, as well as the quality of the CT tech performing the scan.”

During the study period, 203 patients presented at the TTC with prior scans conducted at an NTC.

The mean age of the patients was 43 years; most (67%) were men. The mean Injury Severity Score was 16; 97% had experienced blunt trauma. Shock was present in 3% and a traumatic brain injury in 8%. Repeat scans were most common for neck and cervical spine injuries (54%) and thoracic/lumbar spine injuries (53%), and least common for chest injuries (32%).

An inadequate NTC work-up as judged by the TTC attending was the most common reason for obtaining new images (76%). Poor image quality was the next most common reason (31%).

Among the 203 patients, 99 (49%) had a type A error. Of these injuries missed on the initial scan, 90% were considered to be clinically significant.

Type B errors occurred in 15% of patients. Type C errors (new injuries in different body area) occurred in 54% of patients and, of these, 76% were considered clinically significant. Type D errors (new injuries seen in any imaging of any area) occurred in 73% of patients.

“This study confirms that images are often repeated or completed after having images done at NTCs,” Dr Bonds said. “Relying on NTC image interpretation can lead to undertreating our patients. One potential solution to this issue could be image sharing between NTCs and TTCs. This might reduce both the rate of missed injuries and the need for repeat scans.”

Cutaneous Eruption Reported in Pregnant Woman With Locally Acquired Zika Virus

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Zika presented in a young, pregnant Florida woman as erythematous follicular macules and papules on the trunk and arms, scattered tender pink papules on the palms, and a few petechiae on the hard palate, according to a report in the New England Journal of Medicine.

The report advises how Zika virus may present during pregnancy. “Medical providers on the front line should be aware of the constellation of symptoms in patients reporting travel to endemic areas, including areas in Southern Florida, where other non-travel-associated cases have been confirmed,” wrote investigators led by Lucy Chen, MD, of the University of Miami.

The 23-year-old woman presented on July 7, 2016 at 23 weeks and 3 days’ gestation with a 3-day history of fever, widespread pruritic rash, and sore throat, which were followed by myalgias and joint pain 2 days later. The cutaneous eruption was noted on physical examination; neither conjunctivitis nor lymphadenopathy was present. The patient and her partner said they had not traveled outside the United States for 2 years.

Zika virus RNA was detected in the woman’s urine and serum specimens with the use of reverse-transcriptase polymerase chain reaction and persisted for 2 weeks in urine samples and for 6 weeks in serum samples. On histopathology, skin lesions revealed a mild perivascular lymphocytic infiltration in the upper dermis, admixed with some neutrophils. Liver and renal functions were normal.

Fetal ultrasonography performed on the day of presentation showed an estimated fetal weight of 644 g (53rd percentile), an estimated head circumference of 221 mm (63rd percentile), and normal intracranial anatomy. Fevers and rash subsided after 3 days of supportive care. Screening for measles, varicella, rubella, syphilis, Epstein-Barr virus, influenza, hepatitis B, hepatitis C, mumps, and dengue was negative.

An initial immunoglobulin M test on July 7 was negative; seroconversion occurred 1 week after presentation and remained positive through delivery.

A full-term infant weighing 2,990 g was delivered vaginally. Neonatal ultrasonography and magnetic resonance imaging of the head showed a normal head size and intracranial anatomy, with no calcifications. Placental tissue was negative for Zika virus, and neonatal laboratory testing revealed no evidence of infection.

The case was confirmed by the Miami-Dade County Department of Health as the first non-travel-associated Zika infection in the United States.

Chen L, Hafeez F, Curry CL, Elgart G. Cutaneous eruption in a U.S. woman with locally acquired Zika virus infection. N Engl J Med. 2017;376(4):400-401. doi:10.1056/NEJMc1610614.

Lab Values Poor Surrogate for Detecting Pediatric Rocky Mountain Spotted Fever in Children

WHITNEY MCKNIGHT

FRONTLINE MEDICAL NEWS

Three fatalities observed in a retrospective analysis of six cases of Rocky Mountain spotted fever (RMSF) in children were associated with either a delayed diagnosis pending laboratory findings or delayed anti-rickettsia treatment, researchers said.

“The fact that all fatal cases died before the convalescent period emphasizes that diagnosis should be based on clinical findings instead of RMSF serologic and histologic testing,” wrote the authors of a study published online in Pediatric Dermatology.

Rechelle Tull of the department of dermatology, Wake Forest University, Winston-Salem, NC, and her colleagues conducted a retrospective review of 3,912 inpatient dermatology consultations over a period of 10 years at a tertiary care center, and identified six patients aged 22 months to 2 years (mean, 5.1 years) diagnosed with RMSF. The patients were evaluated in the months of April, May, and June, and three of the six patients infected with the vector-borne obligate intracellular bacterium, Rickettsia rickettsii, had died within 4 days of hospitalization, according to the authors.

Two of the fatal cases involved delayed anti-rickettsial therapy after the patients were misdiagnosed with group A Streptococcus. None of the six children were initially evaluated for R rickettsii; they averaged three encounters with their clinician before being admitted for acute inpatient care, where they received intravenous doxycycline after nearly a week of symptoms.

“All fatal cases were complicated by neurologic manifestations, including seizures, obtundation, and uncal herniation,” a finding that is consistent with the literature, the authors said.

Although the high-fatality rate might be the result of the small study size, Ms Tull and her coinvestigators concluded that the disease should be considered in all differential diagnoses for children who present with a fever and rash during the summer months in endemic areas, particularly since pediatric cases of the disease are associated with poorer outcomes than adult cases.

Given that RMSF often remains subclinical in its early stages, and typically presents with nonspecific symptoms of fever, rash, headache, and abdominal pain when it does emerge, physicians might be tempted to defer treatment until after serological and histological results are in, as is the standard method. Concerns over doxycycline’s tendency to stain teeth and cause enamel hypoplasia are also common. However, empirical administration could mean the difference between life and death, since treatment within the first 5 days following infection is associated with better outcomes—an algorithm complicated by the fact that symptoms caused by R rickettsii have been known to take as long as 21 days to appear.

In the study, Ms Tull and her colleagues found that the average time between exposure to the tick and the onset of symptoms was 6.6 days (range, 1-21 days).

Currently, there are no diagnostic tests “that reliably diagnose RMSF during the first 7 days of illness,” and most patients “do not develop detectable antibodies until the second week of illness,” the investigators reported. Even then, sensitivity of indirect fluorescent antibody serum testing after the second week of illness is only between 86% and 94%, they noted. Further, the sensitivity of immunohistochemical (IHC) tissue staining has been reported at 70%, and false-negative IHC results are common in acute disease when antibody response is harder to detect.

Ms Tull and her colleagues found that five of the six patients in their study had negative IHC testing; two of the six had positive serum antibody titers. For this reason, they concluded that RMSF diagnosis should be based on “clinical history, examination, and laboratory abnormalities” rather than laboratory testing, and urged that “prompt treatment should be instituted empirically.”

Tull R, Ahn C, Daniel A, Yosipovitch G, Strowd LC. Retrospective study of Rocky Mountain spotted fever in children. Pediatr Dermatol. 2016 Dec 19. doi:10.1111/pde.13053. [Epub ahead of print]

BY JEFF BAUER

A large retrospective analysis found a wide variation in opioid prescribing among emergency physicians (EPs) working within the same ED. The study also found that Medicare patients treated by EPs who wrote the most prescriptions for opioids were more likely to use opioids for 6 months after their ED visit than were those treated by EPs who wrote fewer opioid prescriptions.

Researchers evaluated initial visits to an ED by approximately 378,000 Medicare beneficiaries (average age: 68 years) from 2008 through 2011. None of these patients had received a prescription for an opioid in the 6 months before the ED visit, and none of the visits resulted in a hospital admission. Prescriptions for opioids (excluding methadone) were identified by the national drug code in the Medicare Part D database. An opioid prescription was attributed to the treating EP if the patient filled the prescription within 3 days after the ED visit.

Investigators categorized the treating EPs in this study as “high-intensity” or “low-intensity” opioid prescribers by calculating the proportion of all ED visits that resulted in an opioid prescription being filled. They then grouped the EPs into quartiles of opioid prescribing within each hospital. High-intensity prescribers were those in the top quartile of opioid prescribing rates, and low-intensity prescribers were those in the bottom quartile.

The primary outcome was long-term opioid use, defined as 6 months or more of opioids supplied in the 12 months after the initial ED visit. This did not include prescriptions filled within 30 days of the initial visit.

Overall, approximately 215,700 patients were treated by low-intensity prescribers and 162,000 by high-intensity prescribers. In general, the patient characteristics and diagnoses were similar in both groups. The rate of opioid prescribing of high-intensity prescribers was approximately triple the rate of low-intensity prescribers. High-intensity prescribers provided an opioid prescription for 21.4% of ED visits, compared to 7.3% among low-intensity prescribers.

Long-term opioid use at 12 months was significantly higher among patients who had been initially treated by high-intensity prescribers compared to those who had been treated by low-intensity prescribers (1.51% vs 1.16%; unadjusted odds ratio [OR], 1.31). There was minimal change in this difference after the results were adjusted for the patients’ age, race, sex, disability status, and presence of chronic conditions (OR, 1.30). The number needed to harm was calculated as 49, meaning theoretically, for every 49 patients who received a new opioid prescription in the ED, one would become a long-term user. The authors noted, however, that “…prescriptions provided by other physicians in the months after an [ED] visit are necessary for long-term opioid use to take hold.”

Researchers pointed out several limitations to their study. Because the study was observational, it could not establish causality. Researchers were not able to directly attribute opioid prescriptions to the treating EPs, but instead used prescriptions filled within 3 days of an ED visits as a surrogate; some opioid prescriptions could have been written by another clinician, such as the patient’s primary care physician during a follow-up visit. Because the study focused on Medicare patients, the results may not be applicable to younger patients. Based on their analysis, researchers could not determine whether an opioid prescription was appropriate, and therefore they could not quantify the extent of opioid overprescribing.

For more on EPs and opioid prescribing, see “The New Opioid Epidemic and the Law of Unintended Consequences” by Emergency Medicine Editor in Chief Neal Flomenbaum, MD (Emergency Medicine. 2017;49[2]:52) and “The New Opioid Epidemic: Prescriptions, Synthetics, and Street Drugs” by Rama B. Rao, MD and Emergency Medicine Associate Editor, Toxicology Lewis S. Nelson, MD (Emergency Medicine. 2017;49[2]:64-70).

Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med. 2017;376(7):663-673. doi:10.1056/NEJMsa1610524.

Lower Admission Rates, Other Factors Tied to High Rate of Death Soon After ED Discharge Among Older Adults

BY JEFF BAUER

Each year, approximately 10,000 older adult patients die within 7 days of discharge from an ED in the United States, despite having no obvious life-threatening illness, according to a large retrospective study. Emergency departments with lower rates of inpatient admission from the ED, lower patient volumes, and lower charges had significantly higher rates of death after discharge.

Researchers evaluated Medicare claims data related to slightly more than 10 million ED visits from 2007 to 2012. Because the goal was to study generally healthy patients, the following patients were excluded: individuals who were age 90 years and older; were receiving palliative or hospice care; or had received a life-limiting diagnosis, such as a myocardial infarction (MI) or a malignancy, either in the ED or in the year prior to the ED visit. The primary outcome was death within 7 days after discharge from an ED. The cause of death was determined by linking claims to death certificates; this information was available only for a subset of patients who visited an ED in 2007 or 2008.

Overall, during the 6-year study, 0.12% of discharged patients died within 7 days of discharge; this translates to more than 10,000 early deaths per year nationally. The leading causes of death were atherosclerotic heart disease (13.6%), MI (10.3%), and chronic obstructive pulmonary disease (9.6%).

Emergency departments ranked in the lowest fifth for admission rates admitted 15% of patients, compared to 56% of patients at EDs with the highest admission rates. The early death rate of patients treated at EDs with the lowest rates of inpatient admissions from the ED was 3.4 times higher than the death rate seen in EDs with the highest inpatient admission rates (0.27% vs 0.08%, respectively). This was true despite the fact that EDs with low-admission rates treated healthier patients, as evidenced by the overall 7-day mortality rate of all patients treated in the ED, whether they were admitted or discharged. Emergency departments that saw higher volumes of patients and had higher charges for visits had significantly fewer deaths.

Obermeyer Z, Cohn B, Wilson M, Jena AB, Cutler DM. Early death after discharge from emergency departments: analysis of national US insurance claims data. BMJ. 2017;356:j239. doi:10.1136/bmj.j239.

Tertiary Center Repeat Computed Tomography Scans Find Additional Injuries

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Imaging obtained at nontertiary trauma centers (NTCs) probably does not tell the whole story of a trauma patient’s injuries, according to a new retrospective study.

Repeat scans done at a Level 1 trauma center identified new injuries in 76% of patients who were transferred, Morgan Bonds, MD, reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma. About half of these previously unobserved injuries were considered clinically significant, said Dr Bonds, a surgical resident at the University of Oklahoma, Oklahoma City.

Her study examined imaging and clinical assessment of 203 trauma patients who were initially worked up at an NTC, and then transferred to the Level 1 University of Oklahoma tertiary trauma center (TTC). The facility’s primary radiologist reviewed all of the initial computed tomography (CT) scans while blinded to the NTC interpretation. The initial scans and interpretations were then compared with those done at the TTC.

The team split imaging and interpretation disconnects into four categories:

• Type A errors: A missed injury on the NTC scan. “This represents the expertise and experience of our primary radiologist,” Dr Bonds said.
• Type B errors: Missed injuries on scans where NTC radiologists saw other injuries that the TTC radiologist did not confirm. “This represents the experience of our radiologist and also the inexperience and overreaction of the NTC radiologists.”
• Type C errors: New injuries seen on additional TTC imaging of the same body area. “This represents the quality of the image.”
• Type D errors: New injuries found upon any new imaging, whether of a previously scanned or newly scanned body area. “This represents quality of work-up—the decision of the trauma team to more fully investigate the patient’s injuries, as well as the quality of the CT tech performing the scan.”

During the study period, 203 patients presented at the TTC with prior scans conducted at an NTC.

The mean age of the patients was 43 years; most (67%) were men. The mean Injury Severity Score was 16; 97% had experienced blunt trauma. Shock was present in 3% and a traumatic brain injury in 8%. Repeat scans were most common for neck and cervical spine injuries (54%) and thoracic/lumbar spine injuries (53%), and least common for chest injuries (32%).

An inadequate NTC work-up as judged by the TTC attending was the most common reason for obtaining new images (76%). Poor image quality was the next most common reason (31%).

Among the 203 patients, 99 (49%) had a type A error. Of these injuries missed on the initial scan, 90% were considered to be clinically significant.

Type B errors occurred in 15% of patients. Type C errors (new injuries in different body area) occurred in 54% of patients and, of these, 76% were considered clinically significant. Type D errors (new injuries seen in any imaging of any area) occurred in 73% of patients.

“This study confirms that images are often repeated or completed after having images done at NTCs,” Dr Bonds said. “Relying on NTC image interpretation can lead to undertreating our patients. One potential solution to this issue could be image sharing between NTCs and TTCs. This might reduce both the rate of missed injuries and the need for repeat scans.”

Cutaneous Eruption Reported in Pregnant Woman With Locally Acquired Zika Virus

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Zika presented in a young, pregnant Florida woman as erythematous follicular macules and papules on the trunk and arms, scattered tender pink papules on the palms, and a few petechiae on the hard palate, according to a report in the New England Journal of Medicine.

The report advises how Zika virus may present during pregnancy. “Medical providers on the front line should be aware of the constellation of symptoms in patients reporting travel to endemic areas, including areas in Southern Florida, where other non-travel-associated cases have been confirmed,” wrote investigators led by Lucy Chen, MD, of the University of Miami.

The 23-year-old woman presented on July 7, 2016 at 23 weeks and 3 days’ gestation with a 3-day history of fever, widespread pruritic rash, and sore throat, which were followed by myalgias and joint pain 2 days later. The cutaneous eruption was noted on physical examination; neither conjunctivitis nor lymphadenopathy was present. The patient and her partner said they had not traveled outside the United States for 2 years.

Zika virus RNA was detected in the woman’s urine and serum specimens with the use of reverse-transcriptase polymerase chain reaction and persisted for 2 weeks in urine samples and for 6 weeks in serum samples. On histopathology, skin lesions revealed a mild perivascular lymphocytic infiltration in the upper dermis, admixed with some neutrophils. Liver and renal functions were normal.

Fetal ultrasonography performed on the day of presentation showed an estimated fetal weight of 644 g (53rd percentile), an estimated head circumference of 221 mm (63rd percentile), and normal intracranial anatomy. Fevers and rash subsided after 3 days of supportive care. Screening for measles, varicella, rubella, syphilis, Epstein-Barr virus, influenza, hepatitis B, hepatitis C, mumps, and dengue was negative.

An initial immunoglobulin M test on July 7 was negative; seroconversion occurred 1 week after presentation and remained positive through delivery.

A full-term infant weighing 2,990 g was delivered vaginally. Neonatal ultrasonography and magnetic resonance imaging of the head showed a normal head size and intracranial anatomy, with no calcifications. Placental tissue was negative for Zika virus, and neonatal laboratory testing revealed no evidence of infection.

The case was confirmed by the Miami-Dade County Department of Health as the first non-travel-associated Zika infection in the United States.

Chen L, Hafeez F, Curry CL, Elgart G. Cutaneous eruption in a U.S. woman with locally acquired Zika virus infection. N Engl J Med. 2017;376(4):400-401. doi:10.1056/NEJMc1610614.

Lab Values Poor Surrogate for Detecting Pediatric Rocky Mountain Spotted Fever in Children

WHITNEY MCKNIGHT

FRONTLINE MEDICAL NEWS

Three fatalities observed in a retrospective analysis of six cases of Rocky Mountain spotted fever (RMSF) in children were associated with either a delayed diagnosis pending laboratory findings or delayed anti-rickettsia treatment, researchers said.

“The fact that all fatal cases died before the convalescent period emphasizes that diagnosis should be based on clinical findings instead of RMSF serologic and histologic testing,” wrote the authors of a study published online in Pediatric Dermatology.

Rechelle Tull of the department of dermatology, Wake Forest University, Winston-Salem, NC, and her colleagues conducted a retrospective review of 3,912 inpatient dermatology consultations over a period of 10 years at a tertiary care center, and identified six patients aged 22 months to 2 years (mean, 5.1 years) diagnosed with RMSF. The patients were evaluated in the months of April, May, and June, and three of the six patients infected with the vector-borne obligate intracellular bacterium, Rickettsia rickettsii, had died within 4 days of hospitalization, according to the authors.

Two of the fatal cases involved delayed anti-rickettsial therapy after the patients were misdiagnosed with group A Streptococcus. None of the six children were initially evaluated for R rickettsii; they averaged three encounters with their clinician before being admitted for acute inpatient care, where they received intravenous doxycycline after nearly a week of symptoms.

“All fatal cases were complicated by neurologic manifestations, including seizures, obtundation, and uncal herniation,” a finding that is consistent with the literature, the authors said.

Although the high-fatality rate might be the result of the small study size, Ms Tull and her coinvestigators concluded that the disease should be considered in all differential diagnoses for children who present with a fever and rash during the summer months in endemic areas, particularly since pediatric cases of the disease are associated with poorer outcomes than adult cases.

Given that RMSF often remains subclinical in its early stages, and typically presents with nonspecific symptoms of fever, rash, headache, and abdominal pain when it does emerge, physicians might be tempted to defer treatment until after serological and histological results are in, as is the standard method. Concerns over doxycycline’s tendency to stain teeth and cause enamel hypoplasia are also common. However, empirical administration could mean the difference between life and death, since treatment within the first 5 days following infection is associated with better outcomes—an algorithm complicated by the fact that symptoms caused by R rickettsii have been known to take as long as 21 days to appear.

In the study, Ms Tull and her colleagues found that the average time between exposure to the tick and the onset of symptoms was 6.6 days (range, 1-21 days).

Currently, there are no diagnostic tests “that reliably diagnose RMSF during the first 7 days of illness,” and most patients “do not develop detectable antibodies until the second week of illness,” the investigators reported. Even then, sensitivity of indirect fluorescent antibody serum testing after the second week of illness is only between 86% and 94%, they noted. Further, the sensitivity of immunohistochemical (IHC) tissue staining has been reported at 70%, and false-negative IHC results are common in acute disease when antibody response is harder to detect.

Ms Tull and her colleagues found that five of the six patients in their study had negative IHC testing; two of the six had positive serum antibody titers. For this reason, they concluded that RMSF diagnosis should be based on “clinical history, examination, and laboratory abnormalities” rather than laboratory testing, and urged that “prompt treatment should be instituted empirically.”

Tull R, Ahn C, Daniel A, Yosipovitch G, Strowd LC. Retrospective study of Rocky Mountain spotted fever in children. Pediatr Dermatol. 2016 Dec 19. doi:10.1111/pde.13053. [Epub ahead of print]

BY JEFF BAUER

A large retrospective analysis found a wide variation in opioid prescribing among emergency physicians (EPs) working within the same ED. The study also found that Medicare patients treated by EPs who wrote the most prescriptions for opioids were more likely to use opioids for 6 months after their ED visit than were those treated by EPs who wrote fewer opioid prescriptions.

Researchers evaluated initial visits to an ED by approximately 378,000 Medicare beneficiaries (average age: 68 years) from 2008 through 2011. None of these patients had received a prescription for an opioid in the 6 months before the ED visit, and none of the visits resulted in a hospital admission. Prescriptions for opioids (excluding methadone) were identified by the national drug code in the Medicare Part D database. An opioid prescription was attributed to the treating EP if the patient filled the prescription within 3 days after the ED visit.

Investigators categorized the treating EPs in this study as “high-intensity” or “low-intensity” opioid prescribers by calculating the proportion of all ED visits that resulted in an opioid prescription being filled. They then grouped the EPs into quartiles of opioid prescribing within each hospital. High-intensity prescribers were those in the top quartile of opioid prescribing rates, and low-intensity prescribers were those in the bottom quartile.

The primary outcome was long-term opioid use, defined as 6 months or more of opioids supplied in the 12 months after the initial ED visit. This did not include prescriptions filled within 30 days of the initial visit.

Overall, approximately 215,700 patients were treated by low-intensity prescribers and 162,000 by high-intensity prescribers. In general, the patient characteristics and diagnoses were similar in both groups. The rate of opioid prescribing of high-intensity prescribers was approximately triple the rate of low-intensity prescribers. High-intensity prescribers provided an opioid prescription for 21.4% of ED visits, compared to 7.3% among low-intensity prescribers.

Long-term opioid use at 12 months was significantly higher among patients who had been initially treated by high-intensity prescribers compared to those who had been treated by low-intensity prescribers (1.51% vs 1.16%; unadjusted odds ratio [OR], 1.31). There was minimal change in this difference after the results were adjusted for the patients’ age, race, sex, disability status, and presence of chronic conditions (OR, 1.30). The number needed to harm was calculated as 49, meaning theoretically, for every 49 patients who received a new opioid prescription in the ED, one would become a long-term user. The authors noted, however, that “…prescriptions provided by other physicians in the months after an [ED] visit are necessary for long-term opioid use to take hold.”

Researchers pointed out several limitations to their study. Because the study was observational, it could not establish causality. Researchers were not able to directly attribute opioid prescriptions to the treating EPs, but instead used prescriptions filled within 3 days of an ED visits as a surrogate; some opioid prescriptions could have been written by another clinician, such as the patient’s primary care physician during a follow-up visit. Because the study focused on Medicare patients, the results may not be applicable to younger patients. Based on their analysis, researchers could not determine whether an opioid prescription was appropriate, and therefore they could not quantify the extent of opioid overprescribing.

For more on EPs and opioid prescribing, see “The New Opioid Epidemic and the Law of Unintended Consequences” by Emergency Medicine Editor in Chief Neal Flomenbaum, MD (Emergency Medicine. 2017;49[2]:52) and “The New Opioid Epidemic: Prescriptions, Synthetics, and Street Drugs” by Rama B. Rao, MD and Emergency Medicine Associate Editor, Toxicology Lewis S. Nelson, MD (Emergency Medicine. 2017;49[2]:64-70).

Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med. 2017;376(7):663-673. doi:10.1056/NEJMsa1610524.

Lower Admission Rates, Other Factors Tied to High Rate of Death Soon After ED Discharge Among Older Adults

BY JEFF BAUER

Each year, approximately 10,000 older adult patients die within 7 days of discharge from an ED in the United States, despite having no obvious life-threatening illness, according to a large retrospective study. Emergency departments with lower rates of inpatient admission from the ED, lower patient volumes, and lower charges had significantly higher rates of death after discharge.

Researchers evaluated Medicare claims data related to slightly more than 10 million ED visits from 2007 to 2012. Because the goal was to study generally healthy patients, the following patients were excluded: individuals who were age 90 years and older; were receiving palliative or hospice care; or had received a life-limiting diagnosis, such as a myocardial infarction (MI) or a malignancy, either in the ED or in the year prior to the ED visit. The primary outcome was death within 7 days after discharge from an ED. The cause of death was determined by linking claims to death certificates; this information was available only for a subset of patients who visited an ED in 2007 or 2008.

Overall, during the 6-year study, 0.12% of discharged patients died within 7 days of discharge; this translates to more than 10,000 early deaths per year nationally. The leading causes of death were atherosclerotic heart disease (13.6%), MI (10.3%), and chronic obstructive pulmonary disease (9.6%).

Emergency departments ranked in the lowest fifth for admission rates admitted 15% of patients, compared to 56% of patients at EDs with the highest admission rates. The early death rate of patients treated at EDs with the lowest rates of inpatient admissions from the ED was 3.4 times higher than the death rate seen in EDs with the highest inpatient admission rates (0.27% vs 0.08%, respectively). This was true despite the fact that EDs with low-admission rates treated healthier patients, as evidenced by the overall 7-day mortality rate of all patients treated in the ED, whether they were admitted or discharged. Emergency departments that saw higher volumes of patients and had higher charges for visits had significantly fewer deaths.

Obermeyer Z, Cohn B, Wilson M, Jena AB, Cutler DM. Early death after discharge from emergency departments: analysis of national US insurance claims data. BMJ. 2017;356:j239. doi:10.1136/bmj.j239.

Tertiary Center Repeat Computed Tomography Scans Find Additional Injuries

MICHELE G. SULLIVAN

FRONTLINE MEDICAL NEWS

Imaging obtained at nontertiary trauma centers (NTCs) probably does not tell the whole story of a trauma patient’s injuries, according to a new retrospective study.

Repeat scans done at a Level 1 trauma center identified new injuries in 76% of patients who were transferred, Morgan Bonds, MD, reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma. About half of these previously unobserved injuries were considered clinically significant, said Dr Bonds, a surgical resident at the University of Oklahoma, Oklahoma City.

Her study examined imaging and clinical assessment of 203 trauma patients who were initially worked up at an NTC, and then transferred to the Level 1 University of Oklahoma tertiary trauma center (TTC). The facility’s primary radiologist reviewed all of the initial computed tomography (CT) scans while blinded to the NTC interpretation. The initial scans and interpretations were then compared with those done at the TTC.

The team split imaging and interpretation disconnects into four categories:

• Type A errors: A missed injury on the NTC scan. “This represents the expertise and experience of our primary radiologist,” Dr Bonds said.
• Type B errors: Missed injuries on scans where NTC radiologists saw other injuries that the TTC radiologist did not confirm. “This represents the experience of our radiologist and also the inexperience and overreaction of the NTC radiologists.”
• Type C errors: New injuries seen on additional TTC imaging of the same body area. “This represents the quality of the image.”
• Type D errors: New injuries found upon any new imaging, whether of a previously scanned or newly scanned body area. “This represents quality of work-up—the decision of the trauma team to more fully investigate the patient’s injuries, as well as the quality of the CT tech performing the scan.”

During the study period, 203 patients presented at the TTC with prior scans conducted at an NTC.

The mean age of the patients was 43 years; most (67%) were men. The mean Injury Severity Score was 16; 97% had experienced blunt trauma. Shock was present in 3% and a traumatic brain injury in 8%. Repeat scans were most common for neck and cervical spine injuries (54%) and thoracic/lumbar spine injuries (53%), and least common for chest injuries (32%).

An inadequate NTC work-up as judged by the TTC attending was the most common reason for obtaining new images (76%). Poor image quality was the next most common reason (31%).

Among the 203 patients, 99 (49%) had a type A error. Of these injuries missed on the initial scan, 90% were considered to be clinically significant.

Type B errors occurred in 15% of patients. Type C errors (new injuries in different body area) occurred in 54% of patients and, of these, 76% were considered clinically significant. Type D errors (new injuries seen in any imaging of any area) occurred in 73% of patients.

“This study confirms that images are often repeated or completed after having images done at NTCs,” Dr Bonds said. “Relying on NTC image interpretation can lead to undertreating our patients. One potential solution to this issue could be image sharing between NTCs and TTCs. This might reduce both the rate of missed injuries and the need for repeat scans.”

Cutaneous Eruption Reported in Pregnant Woman With Locally Acquired Zika Virus

M. ALEXANDER OTTO

FRONTLINE MEDICAL NEWS

Zika presented in a young, pregnant Florida woman as erythematous follicular macules and papules on the trunk and arms, scattered tender pink papules on the palms, and a few petechiae on the hard palate, according to a report in the New England Journal of Medicine.

The report advises how Zika virus may present during pregnancy. “Medical providers on the front line should be aware of the constellation of symptoms in patients reporting travel to endemic areas, including areas in Southern Florida, where other non-travel-associated cases have been confirmed,” wrote investigators led by Lucy Chen, MD, of the University of Miami.

The 23-year-old woman presented on July 7, 2016 at 23 weeks and 3 days’ gestation with a 3-day history of fever, widespread pruritic rash, and sore throat, which were followed by myalgias and joint pain 2 days later. The cutaneous eruption was noted on physical examination; neither conjunctivitis nor lymphadenopathy was present. The patient and her partner said they had not traveled outside the United States for 2 years.

Zika virus RNA was detected in the woman’s urine and serum specimens with the use of reverse-transcriptase polymerase chain reaction and persisted for 2 weeks in urine samples and for 6 weeks in serum samples. On histopathology, skin lesions revealed a mild perivascular lymphocytic infiltration in the upper dermis, admixed with some neutrophils. Liver and renal functions were normal.

Fetal ultrasonography performed on the day of presentation showed an estimated fetal weight of 644 g (53rd percentile), an estimated head circumference of 221 mm (63rd percentile), and normal intracranial anatomy. Fevers and rash subsided after 3 days of supportive care. Screening for measles, varicella, rubella, syphilis, Epstein-Barr virus, influenza, hepatitis B, hepatitis C, mumps, and dengue was negative.

An initial immunoglobulin M test on July 7 was negative; seroconversion occurred 1 week after presentation and remained positive through delivery.

A full-term infant weighing 2,990 g was delivered vaginally. Neonatal ultrasonography and magnetic resonance imaging of the head showed a normal head size and intracranial anatomy, with no calcifications. Placental tissue was negative for Zika virus, and neonatal laboratory testing revealed no evidence of infection.

The case was confirmed by the Miami-Dade County Department of Health as the first non-travel-associated Zika infection in the United States.

Chen L, Hafeez F, Curry CL, Elgart G. Cutaneous eruption in a U.S. woman with locally acquired Zika virus infection. N Engl J Med. 2017;376(4):400-401. doi:10.1056/NEJMc1610614.

Lab Values Poor Surrogate for Detecting Pediatric Rocky Mountain Spotted Fever in Children

WHITNEY MCKNIGHT

FRONTLINE MEDICAL NEWS

Three fatalities observed in a retrospective analysis of six cases of Rocky Mountain spotted fever (RMSF) in children were associated with either a delayed diagnosis pending laboratory findings or delayed anti-rickettsia treatment, researchers said.

“The fact that all fatal cases died before the convalescent period emphasizes that diagnosis should be based on clinical findings instead of RMSF serologic and histologic testing,” wrote the authors of a study published online in Pediatric Dermatology.

Rechelle Tull of the department of dermatology, Wake Forest University, Winston-Salem, NC, and her colleagues conducted a retrospective review of 3,912 inpatient dermatology consultations over a period of 10 years at a tertiary care center, and identified six patients aged 22 months to 2 years (mean, 5.1 years) diagnosed with RMSF. The patients were evaluated in the months of April, May, and June, and three of the six patients infected with the vector-borne obligate intracellular bacterium, Rickettsia rickettsii, had died within 4 days of hospitalization, according to the authors.

Two of the fatal cases involved delayed anti-rickettsial therapy after the patients were misdiagnosed with group A Streptococcus. None of the six children were initially evaluated for R rickettsii; they averaged three encounters with their clinician before being admitted for acute inpatient care, where they received intravenous doxycycline after nearly a week of symptoms.

“All fatal cases were complicated by neurologic manifestations, including seizures, obtundation, and uncal herniation,” a finding that is consistent with the literature, the authors said.

Although the high-fatality rate might be the result of the small study size, Ms Tull and her coinvestigators concluded that the disease should be considered in all differential diagnoses for children who present with a fever and rash during the summer months in endemic areas, particularly since pediatric cases of the disease are associated with poorer outcomes than adult cases.

Given that RMSF often remains subclinical in its early stages, and typically presents with nonspecific symptoms of fever, rash, headache, and abdominal pain when it does emerge, physicians might be tempted to defer treatment until after serological and histological results are in, as is the standard method. Concerns over doxycycline’s tendency to stain teeth and cause enamel hypoplasia are also common. However, empirical administration could mean the difference between life and death, since treatment within the first 5 days following infection is associated with better outcomes—an algorithm complicated by the fact that symptoms caused by R rickettsii have been known to take as long as 21 days to appear.

In the study, Ms Tull and her colleagues found that the average time between exposure to the tick and the onset of symptoms was 6.6 days (range, 1-21 days).

Currently, there are no diagnostic tests “that reliably diagnose RMSF during the first 7 days of illness,” and most patients “do not develop detectable antibodies until the second week of illness,” the investigators reported. Even then, sensitivity of indirect fluorescent antibody serum testing after the second week of illness is only between 86% and 94%, they noted. Further, the sensitivity of immunohistochemical (IHC) tissue staining has been reported at 70%, and false-negative IHC results are common in acute disease when antibody response is harder to detect.

Ms Tull and her colleagues found that five of the six patients in their study had negative IHC testing; two of the six had positive serum antibody titers. For this reason, they concluded that RMSF diagnosis should be based on “clinical history, examination, and laboratory abnormalities” rather than laboratory testing, and urged that “prompt treatment should be instituted empirically.”

Tull R, Ahn C, Daniel A, Yosipovitch G, Strowd LC. Retrospective study of Rocky Mountain spotted fever in children. Pediatr Dermatol. 2016 Dec 19. doi:10.1111/pde.13053. [Epub ahead of print]

From the Department of Neuropsychiatry and Behavioral Sceince, University of South Carolina School of Medicine, Columbia, SC.

Abstract

• Objective: To review the identification, clinical assessment and treatment of patients with late-life depression.
• Methods: Review of the literature.
• Results: Depressive symptoms are present in up to 1 in 4 older adults. Comprehensive evaluation of depressive symptoms in this population often requires a multidisciplinary and collaborative approach between primary care, mental health, and other ancillary providers. Key aspects include a detailed history, physical and mental status examinations, cognitive and functional status assessment, and suicide risk assessment. Treatment options include anti-depressants, psychotherapy, and electroconvulsive therapy.
• Conclusion: A systematic approach to evaluating depressive symptoms in the elderly can enhance timely recognition and treatment.

Key words: Late-life depression; clinical assessment; antidepressants; psychotherapy; electroconvulsive therapy.

The U.S. population is aging, and with this comes the potential for increased health care needs. In 2014, there were over 46 million Americans age 65 and over (14.5% of the U.S. population). This number is projected to increase to 88 million by the year 2050 [1]. One in 4 older adults suffers with depressive symptoms that cause distress and functional impairment [2]. The World Health Organization Global Burden of Disease Study found depressive disorders to be the leading cause of disability-adjusted life years (DALYs) and the second leading cause of years lived with disability (YLDs). The burden of disease due to depressive disorders increased by 37.5% between 1990 and 2010, and 10.4% was attributable to aging [3]. These figures underscore the importance of accurate assessment and treatment of depression in the elderly. In this article, we review the identification, clinical assessment, and treatment of patients with late-life depression.

Diagnostic Criteria

Prevalence

It is estimated that 1% to 4% of community-dwelling adults age 65 and older suffer from MDD, with women more likely to be affected than men (prevalence of 4.4% vs. 2.7) [2,5–7]. This estimate is low compared with lifetime prevalence of almost 20% in the general adult population [8]. However, when depressive symptoms that do not meet criteria for MDD are considered, prevalence rates increase up to 25% [2,9]. These estimates also vary by clinical setting, with the highest rates (up to 40%) among elderly patients in long-term care facilities [10,11]. While individuals with subsyndromal depression may experience fewer symptoms than those with MDD, clinically significant distress persists, impacting health and functional status. Depression is associated with overall poor social or occupational functioning, cognitive decline, increased health care utilization and cost, increased morbidity and mortality from medical illness, and increased suicide mortality [5,9,10,12].

Identifying LLD

Accurate identification of LLD also requires recognition of the differences in the presentation of LLD compared with onset in earlier life. Depression in younger adults is often marked by depressed mood and loss of interest [18]. In contrast, older adults may present with increased anger or irritability [5]. Younger adults are more likely to report suicidal thoughts while older patients report feelings of hopelessness and thoughts of death [18]. LLD is often characterized by increased somatic complaints, hypochondriasis, or pain [5,18,19]. Another major difference lies in the presentation of cognitive difficulties. Younger patients typically complain of poor concentration or indecisiveness. Geriatric patients may present with cognitive changes including objective findings of slower processing speed and executive dysfunction on neuropsychological testing [17].

Depression rating scales may aid in identification of LLD. They are not a substitute for clinical diagnosis but can be useful as screening tools. Two commonly utilized depression rating scales are the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9). GDS is a 30-item instrument developed specifically for older adults. Shorter 15-item, 5-item, and 4-item versions exist. The scale utilizes a Yes/No format and can be self- or clinician-administered [20]. One advantage of the GDS lies in its focus on psychological and cognitive aspects of depression rather than neurovegetative symptoms that may overlap with medical illnesses common in older adults [21]. The PHQ-9 is a 9-item self- or clinician-administered screening tool designed for use in primary care settings and has also been validated in geriatric populations [22,23]. The 9 items on this scale correspond to the DSM-5 criteria for major depression. A shorter 2-item version (PHQ-2) has also been validated, and a positive screen on this test should prompt administration of the full-length version. Both versions have approximately 80% sensitivity and specificity in detecting depression. An added advantage of PHQ-9 over GDS is that it can be useful in monitoring treatment response over time [22,23]

Comprehensive Assessment of LLD

The comprehensive assessment of patients with LLD can be carried out by health professionals in both mental health or primary care settings. In a multidisciplinary approach, psychiatrists and mental health professionals have collaborated with primary care providers using depression care managers with successful outcomes in managing depression in older adults [24,25]. Complete evaluation of a patient with suspected LLD begins with a history and physical and mental status examination. Other essential components of the evaluation include assessment of cognition, functional status, and suicide risk. Laboratory and neuroimaging studies may be necessary as well. Due to the comprehensive nature of this assessment, a multidisciplinary approach with collaboration between primary care, psychiatry, psychology, and ancillary services such as social work may be necessary. Multiple patient interactions may be required to complete a thorough evaluation.

History and Mental Status Examination

As with many other psychiatric illnesses, LLD is a clinical diagnosis. A careful history should be obtained initially utilizing open-ended questions. This should be followed by more directed questions as indicated to elicit the presence of depressive symptoms. The history should be obtained from the patient. A relevant collateral informant can be invaluable in the assessment, especially in cases where there is a comorbid neurocognitive disorder. However, the patient’s informed consent must be obtained prior to obtaining collateral information whenever possible. Psychosocial stressors that may have precipitated or may be perpetuating symptoms should be explored. Such stressors may include recent changes in living situation, loss of social support, recent deaths, or financial difficulties. Biological precipitants also need to be explored including presence of physical illness, depressogenic medications, and comorbid alcohol or other substance use. The patient’s past psychiatric history, psychiatric hospitalizations, and past medication trials should be ascertained. Any family history of depression, other psychiatric disorders, substance use disorders, and suicide attempts should be documented. A full mental status exam including cognitive assessment should be completed [21,26].

Cognitive Assessment

Cognitive impairment can be associated with LLD and may be due to the underlying depression or represent a comorbid neurocognitive disorder. Furthermore, the burden of medical illness as well as cerebrovascular and cardiovascular risk factors have been linked to executive dysfunction and reduced processing speed in individuals with LDD [27,28]. Distinguishing between these can be challenging; however, chronology of symptom onset is often helpful. Depression is more likely the etiology of cognitive impairment when depressive symptoms precede onset of cognitive deficits. This type of cognitive impairment is termed dementia syndrome of depression and may improve with treatment of depression [5]. Some patients may progress to develop major cognitive decline, and it remains unclear whether LLD represents a risk factor or prodrome to developing a major neurocognitive disorder [29]. On the other hand, if depression develops later in the course of cognitive decline, there may be an underlying neurocognitive disorder [17]. Up to 20% of individuals with major neurocognitive disorder due to Alzheimer’s disease also have major depression [11]. For these reasons, concomitant assessment of cognition is essential to the evaluation of the older adult presenting with depressive symptoms [30]. Cognitive domains that may be affected include learning and memory, language, attention, perceptual motor abilities, social cognition, and executive function [4]. Many of these domains can be assessed during the mental status examination, with brief cognitive screening tools, or with formal neuropsychological testing.

While there are numerous cognitive screening tools, some commonly used, brief tools include the Mini-Cog, the Folstein Mini-Mental State Exam (MMSE), and the Montreal Cognitive Assessment (MoCA). The Mini-Cog consists of a 3-item registration, delayed recall, and clock drawing test and has several advantages over other screening tools. It is a brief test (taking approximately 3 minutes to administer) with good sensitivity and specificity of 80% or greater. Compared with other cognitive screening tools, it is less influenced by level of education, language, or cultural background [31–33]. The MMSE is a longer screening tool consisting of 19 items and requires about 10 minutes to administer. Unlike the Mini-Cog, performance on the MMSE can be affected by level of education and cultural background. However, the MMSE can be administered serially to monitor changes in cognition over time [34,35]. The MoCA is a 10-minute cognitive screening tool first developed to detect mild cognitive impairment (MCI) [36]. The MoCA consists of 7 subscore sections covering visuospatial/executive function, naming, memory (delayed recall), attention, language, abstraction, and orientation. The total score is 30, and 1 point is added to the score if the testing subject has less than high school/12 years of education. The MoCA has demonstrated better sensitivity than the MMSE for the detection of MCI [36]. Elderly patients with depression often perform poorly on these cognitive screening tests due to apathy and poor effort.

Functional Assessment

The diagnosis of LLD requires that symptoms cause significant distress or interfere with functioning. A functional assessment is especially important in the evaluation of the older adult in that it allows clinicians to determine an individual’s ability to live independently and attend to daily needs. Basic activities of daily living (ADLs) include bathing, dressing, grooming, toileting, and self-transferring. Instrumental activities of daily living (IADLs) include more complex daily activities such as preparing meals, administering medications, driving, managing finances, and using simple electronics such as the telephone or remote control [26]. Impairment in IADLs is associated with increased depression severity. Conversely, the severity of depressive symptoms along with associated cognitive impairment predicts IADL impairment [37]. The Philadelphia Multilevel Assessment Instrument is a tool that can aid in the assessment of ADLs and IADLs and has been utilized in studies examining disability in depressed elderly patients [37,38]. Other available scales to quantify functional status include OARS Physical Activities of Daily Living, OARS Instrumental Activities of Daily Living Scale, and Direct Assessment of Functional Status Scale [26].

Suicide Assessment

Assessment for suicidality is an integral part of all psychiatric evaluations and is especially important in the evaluation of the depressed older adult. According to the Centers for Disease Control and Prevention, the suicide rate for individuals age 65 and older is 16.6 per 100,000, a figure that is comparable to that for individuals 18–64 years of age [39]. Non-Hispanic Caucasian males age 85 and older have the highest rate of completed suicide (56.5 per 100,000), underscoring the importance of a thorough suicide assessment [39]. Suicidality can range from passive thoughts of death and wishing that one were not alive, to active thoughts of self-harm with plan and intent. A Canadian study found 2% of community-dwelling adults age 55 and older had suicidal thoughts over a 12-month period and, of these, 28% had major depression [40]. A suicide assessment begins with inquiring about the presence of suicidal thoughts, plans, and intent. The 3 most frequently used methods of completed suicide in the elderly are firearms (28%), hanging (24%) and poisoning (21%) [41]. Access to weapons or other lethal means of self-harm such has hoarding of medications should be ascertained.

A complete suicide assessment requires attention to suicide risk factors, protective factors, and warning signs of impending suicide. Risk factors for suicide in the older adult include mood disorders, chronic medical illnesses and associated functional impairment, chronic pain, and psychosocial factors such as social isolation [42]. Mood disorders are present in 54% to 87% of cases of completed suicide, with major depression being the most common [42]. Chronic medical illness and pain can result in functional impairment leading to feelings of excessive guilt or being a burden to loved ones. Protective factors such as social connectedness, spirituality, religious beliefs, and cultural attitudes against suicide may serve as buffers against these risk factors [43]. Warning signs of impending suicide may indicate preparations for suicide and include feelings of hopelessness or lack of purpose, feeling trapped, talking about death, threatening suicide, agitation, social withdrawal, increased substance use and reckless behavior. Warning signs should prompt action to ensure the safety of the individual [44,45].

Physical Examination, Laboratory Studies, and Neuroimaging

Evaluation of LLD is not complete without a physical examination and ancillary studies to identify underlying medical conditions possibly contributing to or mimicking depressive symptoms. Routine laboratory studies include complete blood count, complete metabolic panel, thyroid studies, and urine drug screen. Signs and symptoms of underlying medical conditions may necessitate further laboratory studies [46]. Neuroimaging may reveal signs of cerebrovascular disease which can predispose, precipitate, or perpetuate depression in older adults [47].

Treatment

Treatment of LLD can take many forms and occur in various settings. Geriatric psychiatrists have expertise in the assessment and treatment of mental illness in the elderly. Workforce estimates for 2010 revealed 1 geriatric psychiatrist per 10,000 adults age 75 and over. This figure is estimated to decrease to 0.5 per 10,000 by the year 2030, underscoring the importance of increasing the knowledge base of clinicians across specialties who provide care to the depressed elderly [48]. The primary care setting is often the locus of care for depression in older adults; however, studies suggest that patients are often left untreated or undertreated [49]. Collaborative care models whereby mental health care is integrated into primary care have been shown to improve outcomes. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study found that use of care managers to assist primary care providers in identification of depression, offer algorithm-based treatment recommendations, monitor symptoms and medication side effects, and provide follow-up yielded improvement in outcomes. Patients in the intervention group were more likely to receive pharmacotherapy or psychotherapy, achieve remission, and showed greater decline in suicidal ideation [50]. Similar results were found in the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) study in which intervention patients treated under a collaborative care model showed lower depression severity, less functional impairment, and greater reduction in depressive symptoms [25].

Just as a collaborative care model can lead to improved outcomes, the overall strategy of treating depression must be multifaceted. The biopsychosocial model of disease first described in the 1970s emphasizes biological and psychosocial determinants of illness that must be addressed when treatment is considered [51]. This includes nonmodifiable biological factors such as age, gender, and genetic predisposition that may affect treatment options, as well as modifiable biological factors such as comorbid medical illness, medications, or substance use disorders. Psychological factors that can affect depressive symptoms include coping skills and defense mechanisms in the face of stressful life events. Social factors including the role of culture, environment, and family dynamics in disease presentation must be considered as well [52].

Pharmacologic Treatment of LLD

The primary pharmacologic treatment for depression is antidepressants. Treatment consists of 3 phases—acute, continuation, and maintenance. In the acute phase, the goal is remission of current symptoms and restoration of function. The continuation phase, extending up to 6 months after remission, aims to prevent relapse back into a depressive episode. Maintenance therapy is geared at preventing recurrence of future depressive episodes [53]. Studies have found a 50% risk of relapse after 1 episode of depression and 80% after 2 episodes. Up to 20% will develop chronic symptoms. For this reason, maintenance therapy is often necessary for recurrent depression [54].

While cognitive impairment may affect antidepressant efficacy, age does not appear to be a determinant. Gildengers et al examined antidepressant response in young, middle, and older-old patients and found no significant difference in response rates [59]. Early onset versus late onset of first depressive episode also does not predict antidepressant response in patients age 55 and over [60]. There is scant evidence for efficacy of antidepressants in depressed patients with neurocognitive disorders. A 2002 Cochrane review with 4 studies in the meta-analysis (n = 137) concluded that there was weak support for antidepressant efficacy in this population [61]. A 2011 meta-analysis with 330 participants also yielded inconclusive results [62]. The paucity of evidence for antidepressant efficacy in depressed patients with neurocognitive disorders should prompt careful consideration of potential benefits versus adverse effects.

Antidepressants are generally well tolerated in older adults. Side effects vary by medication and contribute to discontinuation in up to 25% of new users (versus 22% for new users who discontinue for reasons other than side effects) [63]. Potential adverse effects shared by most SSRIs and SNRIs include GI disturbance (nausea, diarrhea or constipation), sexual dysfunction, headache, and sleep disturbance [64,65]. In addition, abrupt discontinuation can precipitate serotonin withdrawal syndrome characterized by sensory disturbance (paresthesia, tremor, and irritability) as well as headache, lightheadedness, diaphoresis, insomnia, and agitation. Other medication-specific side effects include risk of seizure with bupropion and sedation with mirtazapine [65].

Despite superiority of antidepressants to placebo in treating depression, up to one-third of patients may not respond to a trial of antidepressants. Sequential treatment protocols such as switching to a different antidepressant or augmentation can increase the proportion of antidepressant responders [66–68]. Studies have found particularly favorable response to augmentation with lithium, with one study achieving a 33% remission rate in treatment- resistant geriatric depression [67,69]. Other pharmacologic augmentation strategies include the addition of mood stabilizers such as lamotrigine, antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone), and psychostimulants [70–73]. Electroconvulsive therapy (ECT) is a nonpharmacologic option for treatment-resistant depression that will be reviewed later.

Psychotherapeutic and Psychosocial Interventions

Psychotherapeutic interventions have demonstrated efficacy in the treatment of geriatric depression, including but not limited to cognitive behavioral therapy (CBT), interpersonal therapy (IPT), problem-solving therapy (PST), reminiscence and life review, and brief psychodynamic psychotherapy [74]. Some older adults may prefer psychotherapy to pharmacologic treatment (57% vs. 43%) [75]. Potential benefits of psychotherapy include ability to directly address psychosocial stressors that may precipitate or perpetuate depressive symptoms. In addition, psychotherapy is associated with few to no side effects and avoids drug interactions. Barriers to employing psychotherapy may include cost and access to trained psychotherapists [76]. Efficacy of several psychotherapeutic approaches in the care of older depressed adults has been examined. CBT, brief psychodynamic psychotherapy, and IPT will be briefly reviewed here.

CBT. Cognitive therapy was first described by Aaron Beck in the 1960s [77]. It is a highly structured therapy built on the premise that beliefs and assumptions an individual holds can influence emotions and behavior. CBT aims to identify maladaptive belief systems, test the validity of these cognitive distortions, and help individuals formulate more realistic cognitions [78]. Symptom improvement results from addressing these cognitive aspects as well as integration of behavioral activation and skills training to overcome maladaptive behavioral patterns [78]. CBT approaches have been applied to older adults with depression and results show acceptability [79] and efficacy in this population [80–82]. A 2008 Cochrane review (n = 153) found CBT to be superior to waitlist controls [82].

Brief psychodynamic psychotherapy. Brief psychodynamic psychotherapy, unlike highly structured CBT, aims to alter behavior by examining how past experiences and unresolved conflicts influence current emotions and behavior. While studies on application to the treatment of geriatric depression are scarce, limited data demonstrate efficacy in treating geriatric depression [81] and no significant difference in outcomes when compared to CBT [82].

IPT. Like CBT, IPT is a structured time-limited psychotherapeutic treatment approach first developed in the late 1960s by Klerman and Weissman [83]. IPT focuses on the impact of interpersonal relationships on depressive symptoms and examines 4 domains: interpersonal conflict, interpersonal deficits, role transitions, and grief [74].

Studies have shown efficacy of IPT in reducing depressive symptoms in the elderly when compared to usual care [84]. Reynolds et al found IPT combined with nortriptyline (a tricyclic antidepressant) to be superior to either nortriptyline alone or IPT alone in preventing recurrent depressive episodes [85]. Interestingly, a similar study investigating the efficacy of IPT in combination with paroxetine (an SSRI) failed to show added benefit of IPT in preventing recurrence, suggesting that further studies are needed [86].

Psychosocial interventions are integral in the care of the elderly depressed patient. Studies have shown positive benefits of aerobic exercise on depressive symptoms [87]. Yoga, Tai Chi, and other mindfulness-based exercises can increase sense of emotional and physical wellbeing [88–90]. Spirituality, religious beliefs, and involvement with a faith group may be protective against development of mental illness while at the same time provide avenues for increased social connectedness [91]. These and other avenues for socialization should be encouraged as part of the treatment plan for older depressed patients [92]

Electroconvulsive Therapy

ECT is indicated for the treatment of mood and psychotic disorders and has demonstrated efficacy in the treatment of severe depression [93]. It is typically initiated when patients fail to respond to pharmacotherapy and psychotherapy. Circumstances in which ECT can be considered first-line treatment include situations that require a rapid response (severe inanition, weight loss, or suicidality), situations where risks of ECT are lower than that of alternative treatments, previous positive response to ECT, or strong patient preference [94]. ECT is performed under general anesthesia and involves the induction of a generalized tonic-clonic seizure, which is theorized to enhance serotonergic, noradrenergic, and dopaminergic neurotransmission. A typical course of ECT involves treatments 3 times a week for an average of 6 to 12 treatments in total [95]. Elderly patients and those suffering from severe depression with psychotic features respond more robustly to ECT [93,96]. Estimated remission rates after an ECT series have been higher than 80% [93], making this modality the most effective treatment for severe depression to date.

Conclusion

As the population continues to age, clinicians are increasingly likely to encounter patients with late-life depression. A thorough evaluation includes not only assessment of depressive symptoms, but also cognitive, functional, and suicide assessment. Treatment options include pharmaco-therapy, psychotherapy, and in some cases electroconvulsive therapy. Utilization of assessment and treatment nuances unique to the geriatric population, with a multidisciplinary and collaborative approach involving primary care, mental health, and other ancillary providers, will serve to ultimately enhance patient care.

Corresponding author: Corresponding author: Juliet Glover, MD, Dept. of Neuropsychiatry and Behavioral Science, Univ. of South Carolina School of Medicine, 15 Medical Park, Suite 301, Columbia, SC 29203, [email protected].

Financial disclosures: None reported.

Author contributions: conception and design, JAG, SS; drafting of article, JAG, SS; critical revision of the article, JAG, SS.

From the Department of Neuropsychiatry and Behavioral Sceince, University of South Carolina School of Medicine, Columbia, SC.

Abstract

• Objective: To review the identification, clinical assessment and treatment of patients with late-life depression.
• Methods: Review of the literature.
• Results: Depressive symptoms are present in up to 1 in 4 older adults. Comprehensive evaluation of depressive symptoms in this population often requires a multidisciplinary and collaborative approach between primary care, mental health, and other ancillary providers. Key aspects include a detailed history, physical and mental status examinations, cognitive and functional status assessment, and suicide risk assessment. Treatment options include anti-depressants, psychotherapy, and electroconvulsive therapy.
• Conclusion: A systematic approach to evaluating depressive symptoms in the elderly can enhance timely recognition and treatment.

Key words: Late-life depression; clinical assessment; antidepressants; psychotherapy; electroconvulsive therapy.

The U.S. population is aging, and with this comes the potential for increased health care needs. In 2014, there were over 46 million Americans age 65 and over (14.5% of the U.S. population). This number is projected to increase to 88 million by the year 2050 [1]. One in 4 older adults suffers with depressive symptoms that cause distress and functional impairment [2]. The World Health Organization Global Burden of Disease Study found depressive disorders to be the leading cause of disability-adjusted life years (DALYs) and the second leading cause of years lived with disability (YLDs). The burden of disease due to depressive disorders increased by 37.5% between 1990 and 2010, and 10.4% was attributable to aging [3]. These figures underscore the importance of accurate assessment and treatment of depression in the elderly. In this article, we review the identification, clinical assessment, and treatment of patients with late-life depression.

Diagnostic Criteria

Prevalence

It is estimated that 1% to 4% of community-dwelling adults age 65 and older suffer from MDD, with women more likely to be affected than men (prevalence of 4.4% vs. 2.7) [2,5–7]. This estimate is low compared with lifetime prevalence of almost 20% in the general adult population [8]. However, when depressive symptoms that do not meet criteria for MDD are considered, prevalence rates increase up to 25% [2,9]. These estimates also vary by clinical setting, with the highest rates (up to 40%) among elderly patients in long-term care facilities [10,11]. While individuals with subsyndromal depression may experience fewer symptoms than those with MDD, clinically significant distress persists, impacting health and functional status. Depression is associated with overall poor social or occupational functioning, cognitive decline, increased health care utilization and cost, increased morbidity and mortality from medical illness, and increased suicide mortality [5,9,10,12].

Identifying LLD

Accurate identification of LLD also requires recognition of the differences in the presentation of LLD compared with onset in earlier life. Depression in younger adults is often marked by depressed mood and loss of interest [18]. In contrast, older adults may present with increased anger or irritability [5]. Younger adults are more likely to report suicidal thoughts while older patients report feelings of hopelessness and thoughts of death [18]. LLD is often characterized by increased somatic complaints, hypochondriasis, or pain [5,18,19]. Another major difference lies in the presentation of cognitive difficulties. Younger patients typically complain of poor concentration or indecisiveness. Geriatric patients may present with cognitive changes including objective findings of slower processing speed and executive dysfunction on neuropsychological testing [17].

Depression rating scales may aid in identification of LLD. They are not a substitute for clinical diagnosis but can be useful as screening tools. Two commonly utilized depression rating scales are the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9). GDS is a 30-item instrument developed specifically for older adults. Shorter 15-item, 5-item, and 4-item versions exist. The scale utilizes a Yes/No format and can be self- or clinician-administered [20]. One advantage of the GDS lies in its focus on psychological and cognitive aspects of depression rather than neurovegetative symptoms that may overlap with medical illnesses common in older adults [21]. The PHQ-9 is a 9-item self- or clinician-administered screening tool designed for use in primary care settings and has also been validated in geriatric populations [22,23]. The 9 items on this scale correspond to the DSM-5 criteria for major depression. A shorter 2-item version (PHQ-2) has also been validated, and a positive screen on this test should prompt administration of the full-length version. Both versions have approximately 80% sensitivity and specificity in detecting depression. An added advantage of PHQ-9 over GDS is that it can be useful in monitoring treatment response over time [22,23]

Comprehensive Assessment of LLD

The comprehensive assessment of patients with LLD can be carried out by health professionals in both mental health or primary care settings. In a multidisciplinary approach, psychiatrists and mental health professionals have collaborated with primary care providers using depression care managers with successful outcomes in managing depression in older adults [24,25]. Complete evaluation of a patient with suspected LLD begins with a history and physical and mental status examination. Other essential components of the evaluation include assessment of cognition, functional status, and suicide risk. Laboratory and neuroimaging studies may be necessary as well. Due to the comprehensive nature of this assessment, a multidisciplinary approach with collaboration between primary care, psychiatry, psychology, and ancillary services such as social work may be necessary. Multiple patient interactions may be required to complete a thorough evaluation.

History and Mental Status Examination

As with many other psychiatric illnesses, LLD is a clinical diagnosis. A careful history should be obtained initially utilizing open-ended questions. This should be followed by more directed questions as indicated to elicit the presence of depressive symptoms. The history should be obtained from the patient. A relevant collateral informant can be invaluable in the assessment, especially in cases where there is a comorbid neurocognitive disorder. However, the patient’s informed consent must be obtained prior to obtaining collateral information whenever possible. Psychosocial stressors that may have precipitated or may be perpetuating symptoms should be explored. Such stressors may include recent changes in living situation, loss of social support, recent deaths, or financial difficulties. Biological precipitants also need to be explored including presence of physical illness, depressogenic medications, and comorbid alcohol or other substance use. The patient’s past psychiatric history, psychiatric hospitalizations, and past medication trials should be ascertained. Any family history of depression, other psychiatric disorders, substance use disorders, and suicide attempts should be documented. A full mental status exam including cognitive assessment should be completed [21,26].

Cognitive Assessment

Cognitive impairment can be associated with LLD and may be due to the underlying depression or represent a comorbid neurocognitive disorder. Furthermore, the burden of medical illness as well as cerebrovascular and cardiovascular risk factors have been linked to executive dysfunction and reduced processing speed in individuals with LDD [27,28]. Distinguishing between these can be challenging; however, chronology of symptom onset is often helpful. Depression is more likely the etiology of cognitive impairment when depressive symptoms precede onset of cognitive deficits. This type of cognitive impairment is termed dementia syndrome of depression and may improve with treatment of depression [5]. Some patients may progress to develop major cognitive decline, and it remains unclear whether LLD represents a risk factor or prodrome to developing a major neurocognitive disorder [29]. On the other hand, if depression develops later in the course of cognitive decline, there may be an underlying neurocognitive disorder [17]. Up to 20% of individuals with major neurocognitive disorder due to Alzheimer’s disease also have major depression [11]. For these reasons, concomitant assessment of cognition is essential to the evaluation of the older adult presenting with depressive symptoms [30]. Cognitive domains that may be affected include learning and memory, language, attention, perceptual motor abilities, social cognition, and executive function [4]. Many of these domains can be assessed during the mental status examination, with brief cognitive screening tools, or with formal neuropsychological testing.

While there are numerous cognitive screening tools, some commonly used, brief tools include the Mini-Cog, the Folstein Mini-Mental State Exam (MMSE), and the Montreal Cognitive Assessment (MoCA). The Mini-Cog consists of a 3-item registration, delayed recall, and clock drawing test and has several advantages over other screening tools. It is a brief test (taking approximately 3 minutes to administer) with good sensitivity and specificity of 80% or greater. Compared with other cognitive screening tools, it is less influenced by level of education, language, or cultural background [31–33]. The MMSE is a longer screening tool consisting of 19 items and requires about 10 minutes to administer. Unlike the Mini-Cog, performance on the MMSE can be affected by level of education and cultural background. However, the MMSE can be administered serially to monitor changes in cognition over time [34,35]. The MoCA is a 10-minute cognitive screening tool first developed to detect mild cognitive impairment (MCI) [36]. The MoCA consists of 7 subscore sections covering visuospatial/executive function, naming, memory (delayed recall), attention, language, abstraction, and orientation. The total score is 30, and 1 point is added to the score if the testing subject has less than high school/12 years of education. The MoCA has demonstrated better sensitivity than the MMSE for the detection of MCI [36]. Elderly patients with depression often perform poorly on these cognitive screening tests due to apathy and poor effort.

Functional Assessment

The diagnosis of LLD requires that symptoms cause significant distress or interfere with functioning. A functional assessment is especially important in the evaluation of the older adult in that it allows clinicians to determine an individual’s ability to live independently and attend to daily needs. Basic activities of daily living (ADLs) include bathing, dressing, grooming, toileting, and self-transferring. Instrumental activities of daily living (IADLs) include more complex daily activities such as preparing meals, administering medications, driving, managing finances, and using simple electronics such as the telephone or remote control [26]. Impairment in IADLs is associated with increased depression severity. Conversely, the severity of depressive symptoms along with associated cognitive impairment predicts IADL impairment [37]. The Philadelphia Multilevel Assessment Instrument is a tool that can aid in the assessment of ADLs and IADLs and has been utilized in studies examining disability in depressed elderly patients [37,38]. Other available scales to quantify functional status include OARS Physical Activities of Daily Living, OARS Instrumental Activities of Daily Living Scale, and Direct Assessment of Functional Status Scale [26].

Suicide Assessment

Assessment for suicidality is an integral part of all psychiatric evaluations and is especially important in the evaluation of the depressed older adult. According to the Centers for Disease Control and Prevention, the suicide rate for individuals age 65 and older is 16.6 per 100,000, a figure that is comparable to that for individuals 18–64 years of age [39]. Non-Hispanic Caucasian males age 85 and older have the highest rate of completed suicide (56.5 per 100,000), underscoring the importance of a thorough suicide assessment [39]. Suicidality can range from passive thoughts of death and wishing that one were not alive, to active thoughts of self-harm with plan and intent. A Canadian study found 2% of community-dwelling adults age 55 and older had suicidal thoughts over a 12-month period and, of these, 28% had major depression [40]. A suicide assessment begins with inquiring about the presence of suicidal thoughts, plans, and intent. The 3 most frequently used methods of completed suicide in the elderly are firearms (28%), hanging (24%) and poisoning (21%) [41]. Access to weapons or other lethal means of self-harm such has hoarding of medications should be ascertained.

A complete suicide assessment requires attention to suicide risk factors, protective factors, and warning signs of impending suicide. Risk factors for suicide in the older adult include mood disorders, chronic medical illnesses and associated functional impairment, chronic pain, and psychosocial factors such as social isolation [42]. Mood disorders are present in 54% to 87% of cases of completed suicide, with major depression being the most common [42]. Chronic medical illness and pain can result in functional impairment leading to feelings of excessive guilt or being a burden to loved ones. Protective factors such as social connectedness, spirituality, religious beliefs, and cultural attitudes against suicide may serve as buffers against these risk factors [43]. Warning signs of impending suicide may indicate preparations for suicide and include feelings of hopelessness or lack of purpose, feeling trapped, talking about death, threatening suicide, agitation, social withdrawal, increased substance use and reckless behavior. Warning signs should prompt action to ensure the safety of the individual [44,45].

Physical Examination, Laboratory Studies, and Neuroimaging

Evaluation of LLD is not complete without a physical examination and ancillary studies to identify underlying medical conditions possibly contributing to or mimicking depressive symptoms. Routine laboratory studies include complete blood count, complete metabolic panel, thyroid studies, and urine drug screen. Signs and symptoms of underlying medical conditions may necessitate further laboratory studies [46]. Neuroimaging may reveal signs of cerebrovascular disease which can predispose, precipitate, or perpetuate depression in older adults [47].

Treatment

Treatment of LLD can take many forms and occur in various settings. Geriatric psychiatrists have expertise in the assessment and treatment of mental illness in the elderly. Workforce estimates for 2010 revealed 1 geriatric psychiatrist per 10,000 adults age 75 and over. This figure is estimated to decrease to 0.5 per 10,000 by the year 2030, underscoring the importance of increasing the knowledge base of clinicians across specialties who provide care to the depressed elderly [48]. The primary care setting is often the locus of care for depression in older adults; however, studies suggest that patients are often left untreated or undertreated [49]. Collaborative care models whereby mental health care is integrated into primary care have been shown to improve outcomes. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study found that use of care managers to assist primary care providers in identification of depression, offer algorithm-based treatment recommendations, monitor symptoms and medication side effects, and provide follow-up yielded improvement in outcomes. Patients in the intervention group were more likely to receive pharmacotherapy or psychotherapy, achieve remission, and showed greater decline in suicidal ideation [50]. Similar results were found in the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) study in which intervention patients treated under a collaborative care model showed lower depression severity, less functional impairment, and greater reduction in depressive symptoms [25].

Just as a collaborative care model can lead to improved outcomes, the overall strategy of treating depression must be multifaceted. The biopsychosocial model of disease first described in the 1970s emphasizes biological and psychosocial determinants of illness that must be addressed when treatment is considered [51]. This includes nonmodifiable biological factors such as age, gender, and genetic predisposition that may affect treatment options, as well as modifiable biological factors such as comorbid medical illness, medications, or substance use disorders. Psychological factors that can affect depressive symptoms include coping skills and defense mechanisms in the face of stressful life events. Social factors including the role of culture, environment, and family dynamics in disease presentation must be considered as well [52].

Pharmacologic Treatment of LLD

The primary pharmacologic treatment for depression is antidepressants. Treatment consists of 3 phases—acute, continuation, and maintenance. In the acute phase, the goal is remission of current symptoms and restoration of function. The continuation phase, extending up to 6 months after remission, aims to prevent relapse back into a depressive episode. Maintenance therapy is geared at preventing recurrence of future depressive episodes [53]. Studies have found a 50% risk of relapse after 1 episode of depression and 80% after 2 episodes. Up to 20% will develop chronic symptoms. For this reason, maintenance therapy is often necessary for recurrent depression [54].

While cognitive impairment may affect antidepressant efficacy, age does not appear to be a determinant. Gildengers et al examined antidepressant response in young, middle, and older-old patients and found no significant difference in response rates [59]. Early onset versus late onset of first depressive episode also does not predict antidepressant response in patients age 55 and over [60]. There is scant evidence for efficacy of antidepressants in depressed patients with neurocognitive disorders. A 2002 Cochrane review with 4 studies in the meta-analysis (n = 137) concluded that there was weak support for antidepressant efficacy in this population [61]. A 2011 meta-analysis with 330 participants also yielded inconclusive results [62]. The paucity of evidence for antidepressant efficacy in depressed patients with neurocognitive disorders should prompt careful consideration of potential benefits versus adverse effects.

Antidepressants are generally well tolerated in older adults. Side effects vary by medication and contribute to discontinuation in up to 25% of new users (versus 22% for new users who discontinue for reasons other than side effects) [63]. Potential adverse effects shared by most SSRIs and SNRIs include GI disturbance (nausea, diarrhea or constipation), sexual dysfunction, headache, and sleep disturbance [64,65]. In addition, abrupt discontinuation can precipitate serotonin withdrawal syndrome characterized by sensory disturbance (paresthesia, tremor, and irritability) as well as headache, lightheadedness, diaphoresis, insomnia, and agitation. Other medication-specific side effects include risk of seizure with bupropion and sedation with mirtazapine [65].

Despite superiority of antidepressants to placebo in treating depression, up to one-third of patients may not respond to a trial of antidepressants. Sequential treatment protocols such as switching to a different antidepressant or augmentation can increase the proportion of antidepressant responders [66–68]. Studies have found particularly favorable response to augmentation with lithium, with one study achieving a 33% remission rate in treatment- resistant geriatric depression [67,69]. Other pharmacologic augmentation strategies include the addition of mood stabilizers such as lamotrigine, antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone), and psychostimulants [70–73]. Electroconvulsive therapy (ECT) is a nonpharmacologic option for treatment-resistant depression that will be reviewed later.

Psychotherapeutic and Psychosocial Interventions

Psychotherapeutic interventions have demonstrated efficacy in the treatment of geriatric depression, including but not limited to cognitive behavioral therapy (CBT), interpersonal therapy (IPT), problem-solving therapy (PST), reminiscence and life review, and brief psychodynamic psychotherapy [74]. Some older adults may prefer psychotherapy to pharmacologic treatment (57% vs. 43%) [75]. Potential benefits of psychotherapy include ability to directly address psychosocial stressors that may precipitate or perpetuate depressive symptoms. In addition, psychotherapy is associated with few to no side effects and avoids drug interactions. Barriers to employing psychotherapy may include cost and access to trained psychotherapists [76]. Efficacy of several psychotherapeutic approaches in the care of older depressed adults has been examined. CBT, brief psychodynamic psychotherapy, and IPT will be briefly reviewed here.

CBT. Cognitive therapy was first described by Aaron Beck in the 1960s [77]. It is a highly structured therapy built on the premise that beliefs and assumptions an individual holds can influence emotions and behavior. CBT aims to identify maladaptive belief systems, test the validity of these cognitive distortions, and help individuals formulate more realistic cognitions [78]. Symptom improvement results from addressing these cognitive aspects as well as integration of behavioral activation and skills training to overcome maladaptive behavioral patterns [78]. CBT approaches have been applied to older adults with depression and results show acceptability [79] and efficacy in this population [80–82]. A 2008 Cochrane review (n = 153) found CBT to be superior to waitlist controls [82].

Brief psychodynamic psychotherapy. Brief psychodynamic psychotherapy, unlike highly structured CBT, aims to alter behavior by examining how past experiences and unresolved conflicts influence current emotions and behavior. While studies on application to the treatment of geriatric depression are scarce, limited data demonstrate efficacy in treating geriatric depression [81] and no significant difference in outcomes when compared to CBT [82].

IPT. Like CBT, IPT is a structured time-limited psychotherapeutic treatment approach first developed in the late 1960s by Klerman and Weissman [83]. IPT focuses on the impact of interpersonal relationships on depressive symptoms and examines 4 domains: interpersonal conflict, interpersonal deficits, role transitions, and grief [74].

Studies have shown efficacy of IPT in reducing depressive symptoms in the elderly when compared to usual care [84]. Reynolds et al found IPT combined with nortriptyline (a tricyclic antidepressant) to be superior to either nortriptyline alone or IPT alone in preventing recurrent depressive episodes [85]. Interestingly, a similar study investigating the efficacy of IPT in combination with paroxetine (an SSRI) failed to show added benefit of IPT in preventing recurrence, suggesting that further studies are needed [86].

Psychosocial interventions are integral in the care of the elderly depressed patient. Studies have shown positive benefits of aerobic exercise on depressive symptoms [87]. Yoga, Tai Chi, and other mindfulness-based exercises can increase sense of emotional and physical wellbeing [88–90]. Spirituality, religious beliefs, and involvement with a faith group may be protective against development of mental illness while at the same time provide avenues for increased social connectedness [91]. These and other avenues for socialization should be encouraged as part of the treatment plan for older depressed patients [92]

Electroconvulsive Therapy

ECT is indicated for the treatment of mood and psychotic disorders and has demonstrated efficacy in the treatment of severe depression [93]. It is typically initiated when patients fail to respond to pharmacotherapy and psychotherapy. Circumstances in which ECT can be considered first-line treatment include situations that require a rapid response (severe inanition, weight loss, or suicidality), situations where risks of ECT are lower than that of alternative treatments, previous positive response to ECT, or strong patient preference [94]. ECT is performed under general anesthesia and involves the induction of a generalized tonic-clonic seizure, which is theorized to enhance serotonergic, noradrenergic, and dopaminergic neurotransmission. A typical course of ECT involves treatments 3 times a week for an average of 6 to 12 treatments in total [95]. Elderly patients and those suffering from severe depression with psychotic features respond more robustly to ECT [93,96]. Estimated remission rates after an ECT series have been higher than 80% [93], making this modality the most effective treatment for severe depression to date.

Conclusion

As the population continues to age, clinicians are increasingly likely to encounter patients with late-life depression. A thorough evaluation includes not only assessment of depressive symptoms, but also cognitive, functional, and suicide assessment. Treatment options include pharmaco-therapy, psychotherapy, and in some cases electroconvulsive therapy. Utilization of assessment and treatment nuances unique to the geriatric population, with a multidisciplinary and collaborative approach involving primary care, mental health, and other ancillary providers, will serve to ultimately enhance patient care.

Corresponding author: Corresponding author: Juliet Glover, MD, Dept. of Neuropsychiatry and Behavioral Science, Univ. of South Carolina School of Medicine, 15 Medical Park, Suite 301, Columbia, SC 29203, [email protected].

Financial disclosures: None reported.

Author contributions: conception and design, JAG, SS; drafting of article, JAG, SS; critical revision of the article, JAG, SS.

From the Department of Neuropsychiatry and Behavioral Sceince, University of South Carolina School of Medicine, Columbia, SC.

Abstract

• Objective: To review the identification, clinical assessment and treatment of patients with late-life depression.
• Methods: Review of the literature.
• Results: Depressive symptoms are present in up to 1 in 4 older adults. Comprehensive evaluation of depressive symptoms in this population often requires a multidisciplinary and collaborative approach between primary care, mental health, and other ancillary providers. Key aspects include a detailed history, physical and mental status examinations, cognitive and functional status assessment, and suicide risk assessment. Treatment options include anti-depressants, psychotherapy, and electroconvulsive therapy.
• Conclusion: A systematic approach to evaluating depressive symptoms in the elderly can enhance timely recognition and treatment.

Key words: Late-life depression; clinical assessment; antidepressants; psychotherapy; electroconvulsive therapy.

The U.S. population is aging, and with this comes the potential for increased health care needs. In 2014, there were over 46 million Americans age 65 and over (14.5% of the U.S. population). This number is projected to increase to 88 million by the year 2050 [1]. One in 4 older adults suffers with depressive symptoms that cause distress and functional impairment [2]. The World Health Organization Global Burden of Disease Study found depressive disorders to be the leading cause of disability-adjusted life years (DALYs) and the second leading cause of years lived with disability (YLDs). The burden of disease due to depressive disorders increased by 37.5% between 1990 and 2010, and 10.4% was attributable to aging [3]. These figures underscore the importance of accurate assessment and treatment of depression in the elderly. In this article, we review the identification, clinical assessment, and treatment of patients with late-life depression.

Diagnostic Criteria

Prevalence

It is estimated that 1% to 4% of community-dwelling adults age 65 and older suffer from MDD, with women more likely to be affected than men (prevalence of 4.4% vs. 2.7) [2,5–7]. This estimate is low compared with lifetime prevalence of almost 20% in the general adult population [8]. However, when depressive symptoms that do not meet criteria for MDD are considered, prevalence rates increase up to 25% [2,9]. These estimates also vary by clinical setting, with the highest rates (up to 40%) among elderly patients in long-term care facilities [10,11]. While individuals with subsyndromal depression may experience fewer symptoms than those with MDD, clinically significant distress persists, impacting health and functional status. Depression is associated with overall poor social or occupational functioning, cognitive decline, increased health care utilization and cost, increased morbidity and mortality from medical illness, and increased suicide mortality [5,9,10,12].

Identifying LLD

Accurate identification of LLD also requires recognition of the differences in the presentation of LLD compared with onset in earlier life. Depression in younger adults is often marked by depressed mood and loss of interest [18]. In contrast, older adults may present with increased anger or irritability [5]. Younger adults are more likely to report suicidal thoughts while older patients report feelings of hopelessness and thoughts of death [18]. LLD is often characterized by increased somatic complaints, hypochondriasis, or pain [5,18,19]. Another major difference lies in the presentation of cognitive difficulties. Younger patients typically complain of poor concentration or indecisiveness. Geriatric patients may present with cognitive changes including objective findings of slower processing speed and executive dysfunction on neuropsychological testing [17].

Depression rating scales may aid in identification of LLD. They are not a substitute for clinical diagnosis but can be useful as screening tools. Two commonly utilized depression rating scales are the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9). GDS is a 30-item instrument developed specifically for older adults. Shorter 15-item, 5-item, and 4-item versions exist. The scale utilizes a Yes/No format and can be self- or clinician-administered [20]. One advantage of the GDS lies in its focus on psychological and cognitive aspects of depression rather than neurovegetative symptoms that may overlap with medical illnesses common in older adults [21]. The PHQ-9 is a 9-item self- or clinician-administered screening tool designed for use in primary care settings and has also been validated in geriatric populations [22,23]. The 9 items on this scale correspond to the DSM-5 criteria for major depression. A shorter 2-item version (PHQ-2) has also been validated, and a positive screen on this test should prompt administration of the full-length version. Both versions have approximately 80% sensitivity and specificity in detecting depression. An added advantage of PHQ-9 over GDS is that it can be useful in monitoring treatment response over time [22,23]

Comprehensive Assessment of LLD

The comprehensive assessment of patients with LLD can be carried out by health professionals in both mental health or primary care settings. In a multidisciplinary approach, psychiatrists and mental health professionals have collaborated with primary care providers using depression care managers with successful outcomes in managing depression in older adults [24,25]. Complete evaluation of a patient with suspected LLD begins with a history and physical and mental status examination. Other essential components of the evaluation include assessment of cognition, functional status, and suicide risk. Laboratory and neuroimaging studies may be necessary as well. Due to the comprehensive nature of this assessment, a multidisciplinary approach with collaboration between primary care, psychiatry, psychology, and ancillary services such as social work may be necessary. Multiple patient interactions may be required to complete a thorough evaluation.

History and Mental Status Examination

As with many other psychiatric illnesses, LLD is a clinical diagnosis. A careful history should be obtained initially utilizing open-ended questions. This should be followed by more directed questions as indicated to elicit the presence of depressive symptoms. The history should be obtained from the patient. A relevant collateral informant can be invaluable in the assessment, especially in cases where there is a comorbid neurocognitive disorder. However, the patient’s informed consent must be obtained prior to obtaining collateral information whenever possible. Psychosocial stressors that may have precipitated or may be perpetuating symptoms should be explored. Such stressors may include recent changes in living situation, loss of social support, recent deaths, or financial difficulties. Biological precipitants also need to be explored including presence of physical illness, depressogenic medications, and comorbid alcohol or other substance use. The patient’s past psychiatric history, psychiatric hospitalizations, and past medication trials should be ascertained. Any family history of depression, other psychiatric disorders, substance use disorders, and suicide attempts should be documented. A full mental status exam including cognitive assessment should be completed [21,26].

Cognitive Assessment

Cognitive impairment can be associated with LLD and may be due to the underlying depression or represent a comorbid neurocognitive disorder. Furthermore, the burden of medical illness as well as cerebrovascular and cardiovascular risk factors have been linked to executive dysfunction and reduced processing speed in individuals with LDD [27,28]. Distinguishing between these can be challenging; however, chronology of symptom onset is often helpful. Depression is more likely the etiology of cognitive impairment when depressive symptoms precede onset of cognitive deficits. This type of cognitive impairment is termed dementia syndrome of depression and may improve with treatment of depression [5]. Some patients may progress to develop major cognitive decline, and it remains unclear whether LLD represents a risk factor or prodrome to developing a major neurocognitive disorder [29]. On the other hand, if depression develops later in the course of cognitive decline, there may be an underlying neurocognitive disorder [17]. Up to 20% of individuals with major neurocognitive disorder due to Alzheimer’s disease also have major depression [11]. For these reasons, concomitant assessment of cognition is essential to the evaluation of the older adult presenting with depressive symptoms [30]. Cognitive domains that may be affected include learning and memory, language, attention, perceptual motor abilities, social cognition, and executive function [4]. Many of these domains can be assessed during the mental status examination, with brief cognitive screening tools, or with formal neuropsychological testing.

While there are numerous cognitive screening tools, some commonly used, brief tools include the Mini-Cog, the Folstein Mini-Mental State Exam (MMSE), and the Montreal Cognitive Assessment (MoCA). The Mini-Cog consists of a 3-item registration, delayed recall, and clock drawing test and has several advantages over other screening tools. It is a brief test (taking approximately 3 minutes to administer) with good sensitivity and specificity of 80% or greater. Compared with other cognitive screening tools, it is less influenced by level of education, language, or cultural background [31–33]. The MMSE is a longer screening tool consisting of 19 items and requires about 10 minutes to administer. Unlike the Mini-Cog, performance on the MMSE can be affected by level of education and cultural background. However, the MMSE can be administered serially to monitor changes in cognition over time [34,35]. The MoCA is a 10-minute cognitive screening tool first developed to detect mild cognitive impairment (MCI) [36]. The MoCA consists of 7 subscore sections covering visuospatial/executive function, naming, memory (delayed recall), attention, language, abstraction, and orientation. The total score is 30, and 1 point is added to the score if the testing subject has less than high school/12 years of education. The MoCA has demonstrated better sensitivity than the MMSE for the detection of MCI [36]. Elderly patients with depression often perform poorly on these cognitive screening tests due to apathy and poor effort.

Functional Assessment

The diagnosis of LLD requires that symptoms cause significant distress or interfere with functioning. A functional assessment is especially important in the evaluation of the older adult in that it allows clinicians to determine an individual’s ability to live independently and attend to daily needs. Basic activities of daily living (ADLs) include bathing, dressing, grooming, toileting, and self-transferring. Instrumental activities of daily living (IADLs) include more complex daily activities such as preparing meals, administering medications, driving, managing finances, and using simple electronics such as the telephone or remote control [26]. Impairment in IADLs is associated with increased depression severity. Conversely, the severity of depressive symptoms along with associated cognitive impairment predicts IADL impairment [37]. The Philadelphia Multilevel Assessment Instrument is a tool that can aid in the assessment of ADLs and IADLs and has been utilized in studies examining disability in depressed elderly patients [37,38]. Other available scales to quantify functional status include OARS Physical Activities of Daily Living, OARS Instrumental Activities of Daily Living Scale, and Direct Assessment of Functional Status Scale [26].

Suicide Assessment

Assessment for suicidality is an integral part of all psychiatric evaluations and is especially important in the evaluation of the depressed older adult. According to the Centers for Disease Control and Prevention, the suicide rate for individuals age 65 and older is 16.6 per 100,000, a figure that is comparable to that for individuals 18–64 years of age [39]. Non-Hispanic Caucasian males age 85 and older have the highest rate of completed suicide (56.5 per 100,000), underscoring the importance of a thorough suicide assessment [39]. Suicidality can range from passive thoughts of death and wishing that one were not alive, to active thoughts of self-harm with plan and intent. A Canadian study found 2% of community-dwelling adults age 55 and older had suicidal thoughts over a 12-month period and, of these, 28% had major depression [40]. A suicide assessment begins with inquiring about the presence of suicidal thoughts, plans, and intent. The 3 most frequently used methods of completed suicide in the elderly are firearms (28%), hanging (24%) and poisoning (21%) [41]. Access to weapons or other lethal means of self-harm such has hoarding of medications should be ascertained.

A complete suicide assessment requires attention to suicide risk factors, protective factors, and warning signs of impending suicide. Risk factors for suicide in the older adult include mood disorders, chronic medical illnesses and associated functional impairment, chronic pain, and psychosocial factors such as social isolation [42]. Mood disorders are present in 54% to 87% of cases of completed suicide, with major depression being the most common [42]. Chronic medical illness and pain can result in functional impairment leading to feelings of excessive guilt or being a burden to loved ones. Protective factors such as social connectedness, spirituality, religious beliefs, and cultural attitudes against suicide may serve as buffers against these risk factors [43]. Warning signs of impending suicide may indicate preparations for suicide and include feelings of hopelessness or lack of purpose, feeling trapped, talking about death, threatening suicide, agitation, social withdrawal, increased substance use and reckless behavior. Warning signs should prompt action to ensure the safety of the individual [44,45].

Physical Examination, Laboratory Studies, and Neuroimaging

Evaluation of LLD is not complete without a physical examination and ancillary studies to identify underlying medical conditions possibly contributing to or mimicking depressive symptoms. Routine laboratory studies include complete blood count, complete metabolic panel, thyroid studies, and urine drug screen. Signs and symptoms of underlying medical conditions may necessitate further laboratory studies [46]. Neuroimaging may reveal signs of cerebrovascular disease which can predispose, precipitate, or perpetuate depression in older adults [47].

Treatment

Treatment of LLD can take many forms and occur in various settings. Geriatric psychiatrists have expertise in the assessment and treatment of mental illness in the elderly. Workforce estimates for 2010 revealed 1 geriatric psychiatrist per 10,000 adults age 75 and over. This figure is estimated to decrease to 0.5 per 10,000 by the year 2030, underscoring the importance of increasing the knowledge base of clinicians across specialties who provide care to the depressed elderly [48]. The primary care setting is often the locus of care for depression in older adults; however, studies suggest that patients are often left untreated or undertreated [49]. Collaborative care models whereby mental health care is integrated into primary care have been shown to improve outcomes. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study found that use of care managers to assist primary care providers in identification of depression, offer algorithm-based treatment recommendations, monitor symptoms and medication side effects, and provide follow-up yielded improvement in outcomes. Patients in the intervention group were more likely to receive pharmacotherapy or psychotherapy, achieve remission, and showed greater decline in suicidal ideation [50]. Similar results were found in the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) study in which intervention patients treated under a collaborative care model showed lower depression severity, less functional impairment, and greater reduction in depressive symptoms [25].

Just as a collaborative care model can lead to improved outcomes, the overall strategy of treating depression must be multifaceted. The biopsychosocial model of disease first described in the 1970s emphasizes biological and psychosocial determinants of illness that must be addressed when treatment is considered [51]. This includes nonmodifiable biological factors such as age, gender, and genetic predisposition that may affect treatment options, as well as modifiable biological factors such as comorbid medical illness, medications, or substance use disorders. Psychological factors that can affect depressive symptoms include coping skills and defense mechanisms in the face of stressful life events. Social factors including the role of culture, environment, and family dynamics in disease presentation must be considered as well [52].

Pharmacologic Treatment of LLD

The primary pharmacologic treatment for depression is antidepressants. Treatment consists of 3 phases—acute, continuation, and maintenance. In the acute phase, the goal is remission of current symptoms and restoration of function. The continuation phase, extending up to 6 months after remission, aims to prevent relapse back into a depressive episode. Maintenance therapy is geared at preventing recurrence of future depressive episodes [53]. Studies have found a 50% risk of relapse after 1 episode of depression and 80% after 2 episodes. Up to 20% will develop chronic symptoms. For this reason, maintenance therapy is often necessary for recurrent depression [54].

While cognitive impairment may affect antidepressant efficacy, age does not appear to be a determinant. Gildengers et al examined antidepressant response in young, middle, and older-old patients and found no significant difference in response rates [59]. Early onset versus late onset of first depressive episode also does not predict antidepressant response in patients age 55 and over [60]. There is scant evidence for efficacy of antidepressants in depressed patients with neurocognitive disorders. A 2002 Cochrane review with 4 studies in the meta-analysis (n = 137) concluded that there was weak support for antidepressant efficacy in this population [61]. A 2011 meta-analysis with 330 participants also yielded inconclusive results [62]. The paucity of evidence for antidepressant efficacy in depressed patients with neurocognitive disorders should prompt careful consideration of potential benefits versus adverse effects.

Antidepressants are generally well tolerated in older adults. Side effects vary by medication and contribute to discontinuation in up to 25% of new users (versus 22% for new users who discontinue for reasons other than side effects) [63]. Potential adverse effects shared by most SSRIs and SNRIs include GI disturbance (nausea, diarrhea or constipation), sexual dysfunction, headache, and sleep disturbance [64,65]. In addition, abrupt discontinuation can precipitate serotonin withdrawal syndrome characterized by sensory disturbance (paresthesia, tremor, and irritability) as well as headache, lightheadedness, diaphoresis, insomnia, and agitation. Other medication-specific side effects include risk of seizure with bupropion and sedation with mirtazapine [65].

Despite superiority of antidepressants to placebo in treating depression, up to one-third of patients may not respond to a trial of antidepressants. Sequential treatment protocols such as switching to a different antidepressant or augmentation can increase the proportion of antidepressant responders [66–68]. Studies have found particularly favorable response to augmentation with lithium, with one study achieving a 33% remission rate in treatment- resistant geriatric depression [67,69]. Other pharmacologic augmentation strategies include the addition of mood stabilizers such as lamotrigine, antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone), and psychostimulants [70–73]. Electroconvulsive therapy (ECT) is a nonpharmacologic option for treatment-resistant depression that will be reviewed later.

Psychotherapeutic and Psychosocial Interventions

Psychotherapeutic interventions have demonstrated efficacy in the treatment of geriatric depression, including but not limited to cognitive behavioral therapy (CBT), interpersonal therapy (IPT), problem-solving therapy (PST), reminiscence and life review, and brief psychodynamic psychotherapy [74]. Some older adults may prefer psychotherapy to pharmacologic treatment (57% vs. 43%) [75]. Potential benefits of psychotherapy include ability to directly address psychosocial stressors that may precipitate or perpetuate depressive symptoms. In addition, psychotherapy is associated with few to no side effects and avoids drug interactions. Barriers to employing psychotherapy may include cost and access to trained psychotherapists [76]. Efficacy of several psychotherapeutic approaches in the care of older depressed adults has been examined. CBT, brief psychodynamic psychotherapy, and IPT will be briefly reviewed here.

CBT. Cognitive therapy was first described by Aaron Beck in the 1960s [77]. It is a highly structured therapy built on the premise that beliefs and assumptions an individual holds can influence emotions and behavior. CBT aims to identify maladaptive belief systems, test the validity of these cognitive distortions, and help individuals formulate more realistic cognitions [78]. Symptom improvement results from addressing these cognitive aspects as well as integration of behavioral activation and skills training to overcome maladaptive behavioral patterns [78]. CBT approaches have been applied to older adults with depression and results show acceptability [79] and efficacy in this population [80–82]. A 2008 Cochrane review (n = 153) found CBT to be superior to waitlist controls [82].

Brief psychodynamic psychotherapy. Brief psychodynamic psychotherapy, unlike highly structured CBT, aims to alter behavior by examining how past experiences and unresolved conflicts influence current emotions and behavior. While studies on application to the treatment of geriatric depression are scarce, limited data demonstrate efficacy in treating geriatric depression [81] and no significant difference in outcomes when compared to CBT [82].

IPT. Like CBT, IPT is a structured time-limited psychotherapeutic treatment approach first developed in the late 1960s by Klerman and Weissman [83]. IPT focuses on the impact of interpersonal relationships on depressive symptoms and examines 4 domains: interpersonal conflict, interpersonal deficits, role transitions, and grief [74].

Studies have shown efficacy of IPT in reducing depressive symptoms in the elderly when compared to usual care [84]. Reynolds et al found IPT combined with nortriptyline (a tricyclic antidepressant) to be superior to either nortriptyline alone or IPT alone in preventing recurrent depressive episodes [85]. Interestingly, a similar study investigating the efficacy of IPT in combination with paroxetine (an SSRI) failed to show added benefit of IPT in preventing recurrence, suggesting that further studies are needed [86].

Psychosocial interventions are integral in the care of the elderly depressed patient. Studies have shown positive benefits of aerobic exercise on depressive symptoms [87]. Yoga, Tai Chi, and other mindfulness-based exercises can increase sense of emotional and physical wellbeing [88–90]. Spirituality, religious beliefs, and involvement with a faith group may be protective against development of mental illness while at the same time provide avenues for increased social connectedness [91]. These and other avenues for socialization should be encouraged as part of the treatment plan for older depressed patients [92]

Electroconvulsive Therapy

ECT is indicated for the treatment of mood and psychotic disorders and has demonstrated efficacy in the treatment of severe depression [93]. It is typically initiated when patients fail to respond to pharmacotherapy and psychotherapy. Circumstances in which ECT can be considered first-line treatment include situations that require a rapid response (severe inanition, weight loss, or suicidality), situations where risks of ECT are lower than that of alternative treatments, previous positive response to ECT, or strong patient preference [94]. ECT is performed under general anesthesia and involves the induction of a generalized tonic-clonic seizure, which is theorized to enhance serotonergic, noradrenergic, and dopaminergic neurotransmission. A typical course of ECT involves treatments 3 times a week for an average of 6 to 12 treatments in total [95]. Elderly patients and those suffering from severe depression with psychotic features respond more robustly to ECT [93,96]. Estimated remission rates after an ECT series have been higher than 80% [93], making this modality the most effective treatment for severe depression to date.

Conclusion

As the population continues to age, clinicians are increasingly likely to encounter patients with late-life depression. A thorough evaluation includes not only assessment of depressive symptoms, but also cognitive, functional, and suicide assessment. Treatment options include pharmaco-therapy, psychotherapy, and in some cases electroconvulsive therapy. Utilization of assessment and treatment nuances unique to the geriatric population, with a multidisciplinary and collaborative approach involving primary care, mental health, and other ancillary providers, will serve to ultimately enhance patient care.

Corresponding author: Corresponding author: Juliet Glover, MD, Dept. of Neuropsychiatry and Behavioral Science, Univ. of South Carolina School of Medicine, 15 Medical Park, Suite 301, Columbia, SC 29203, [email protected].

Financial disclosures: None reported.

Author contributions: conception and design, JAG, SS; drafting of article, JAG, SS; critical revision of the article, JAG, SS.

From the University of Colorado Denver, Aurora, CO.

Abstract

• Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
• Methods: Nonsystematic review of the literature.
• Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described. 
• Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.

Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.

In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].

HPV Vaccines

Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].

Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.

Provider Communication About HPV Vaccines

How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].

Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].

Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].

Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].

Possible Strategies for Helping Providers Communicate About HPV Vaccines

Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].

Interpersonal Communication Strategies Shown to Increase HPV Vaccination

Presumptive Communication

One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.

In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.

Motivational Interviewing

A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.

Personalized Communication

Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].

One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].

Focusing Communication on Cancer Prevention

HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.

Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.

Strategies That Are Promising But Not Thoroughly Tested

Helping Parents Create Vaccination Plans

A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.

Treating all Adolescent Vaccines the Same

Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.

Strategies that Probably Don’t Work

Presenting Myths and Facts

Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].

Using Fear Appeals

One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.

Looking Into the Future

Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].

Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.

A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.

Conclusion

With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].

Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, [email protected].

Financial disclosures: None reported.

From the University of Colorado Denver, Aurora, CO.

Abstract

• Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
• Methods: Nonsystematic review of the literature.
• Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described. 
• Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.

Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.

In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].

HPV Vaccines

Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].

Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.

Provider Communication About HPV Vaccines

How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].

Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].

Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].

Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].

Possible Strategies for Helping Providers Communicate About HPV Vaccines

Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].

Interpersonal Communication Strategies Shown to Increase HPV Vaccination

Presumptive Communication

One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.

In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.

Motivational Interviewing

A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.

Personalized Communication

Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].

One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].

Focusing Communication on Cancer Prevention

HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.

Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.

Strategies That Are Promising But Not Thoroughly Tested

Helping Parents Create Vaccination Plans

A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.

Treating all Adolescent Vaccines the Same

Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.

Strategies that Probably Don’t Work

Presenting Myths and Facts

Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].

Using Fear Appeals

One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.

Looking Into the Future

Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].

Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.

A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.

Conclusion

With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].

Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, [email protected].

Financial disclosures: None reported.

From the University of Colorado Denver, Aurora, CO.

Abstract

• Objective: To provide evidence-based guidance on strategies that are likely or unlikely to be successful in navigating HPV vaccine conversations with patients and parents.
• Methods: Nonsystematic review of the literature.
• Results: This review highlights some of the most recent innovations in provider HPV vaccine communication and describes provider communication strategies that have been found to improve adolescent vaccination rates in rigorous scientific studies. Promising strategies for which additional research is needed and strategies that probably do not work are also described. 
• Conclusion: By understanding what works, what may work, and what not to do when it comes to communicating with families about HPV vaccines, providers can be better prepared for maximizing the impact they can have on adolescent HPV vaccination rates.

Key words: human papillomavirus; vaccine hesitancy; health communication; parents; immunization.

In the United States, more than 14 million people newly acquire genital human papillomavirus (HPV) annually, and 75 million Americans are infected at any given time [1]. As the most common sexually transmitted disease, more than 80% of sexually active U.S. adults are estimated to be infected with HPV by the age of 50 [1,2]. Although the majority of infections are “silent” and resolve without clinical sequelae, a proportion of infected individuals will go on to develop HPV-related diseases. In women, these include cervical cancer and pre-cancer (ie, abnormal Pap smears); cancers of the vagina, vulva, anus, and oropharynx; and genital warts [3]. Males also bear a high burden of HPV-related disease in the form of penile, anal, and oropharyngeal cancers, as well as genital warts [3]. While once thought of as primarily a “woman’s disease” [4], recent research demonstrates men are also significantly impacted by HPV—particularly in the form of oropharyngeal cancers, which are 2 to 3 times more common in men than in women [5]. In fact, it is estimated by the year 2020 more men will die of HPV-related oropharyngeal cancer than women will die of cervical cancer [6,7]. The combined cost of HPV-associated cancers and other conditions is estimated to be $8 billion per year in the United States [8–11].

HPV Vaccines

Effective HPV vaccines have been available for females aged 9 to 26 years since 2006 (bivalent and quadrivalent vaccines) and for males aged 9 to 26 since 2010 (quadrivalent vaccine only) [12]. These vaccines have been shown in clinical trials to be highly efficacious in preventing HPV infection, cervical pre-cancer, and anal, vaginal, penile, and vulvar cancers caused by the HPV types covered in the vaccine [2]. Although their effectiveness against head and neck cancer has not been studied in clinical trials, most experts believe that these vaccines will also provide protection against at least a proportion of these cancers [13,14]. In 2015 the U.S. Food and Drug Administration approved licensure of a 9-valent HPV vaccine that will soon replace the quadrivalent vaccine in the U.S. market [15]. The 9-valent vaccine is licensed for both males and females aged 9 to 26 and is expected to prevent an even higher proportion of HPV-related cancers than earlier HPV vaccines due to the protection against 5 additional oncogenic HPV types [15].

Despite the potential of HPV vaccines to drastically reduce the incidence of HPV-related cancers and other diseases, these vaccines are not being as widely used in the United States as was hoped. The most recent national data from 2015 demonstrates that only 41.9% of girls and 28.1% of boys have received all 3 doses recommended in the HPV vaccine series [16]. This level of vaccine utilization is significantly lower than the Healthy People 2020 goal of 80% coverage [17], and also significantly lower than that of other developed countries such as Australia and the United Kingdom, which have achieved vaccination levels of ~70% among their target adolescent populations [18,19]. In the future, these low vaccination levels will likely be mitigated somewhat by the recent approval from the FDA and recent recommendation from the Advisory Committee on Immunization Practices (ACIP) for only 2 doses of the 9-valent HPV vaccine (spaced 6 to 12 months apart) for adolescents less than 15 years of age [20,21]. Three doses are still recommended for those aged 15 to 26 years.

Provider Communication About HPV Vaccines

How providers communicate with parents and patients about HPV vaccines is a key influential factor driving current U.S. adolescent HPV vaccination levels [22,23]. Numerous studies demonstrate that a provider’s recommendation generally has the largest impact on whether or not an adolescent receives the vaccine, even above that of parent factors such as attitudes and beliefs about the vaccine and patient characteristics such as age and insurance status [23–31]. Moreover, parents consistently cite their adolescent’s provider as one of the most trusted and impactful resources for obtaining vaccine information [22,32].

Unfortunately, research also shows that providers often fail to adequately recommend the HPV vaccine for their patients, especially for 11 to 12 year olds for whom the vaccine is preferentially recommended [33,34]. For example, in a national study of parents done in 2013, not being recommended by a provider was one of the top 5 reasons parents of males and of females aged 11 to 17 gave for not getting their adolescent vaccinated against HPV [35]. Supporting this also is a 2014 study of 776 pediatricians and family medicine providers nationally, in which Gilkey and colleagues found that more than 1 out of 4 providers did not highly endorse the HPV vaccine for 11 to 12 year olds despite this having been the recommended practice from ACIP for the prior 8 years for girls and 4 years for boys. This is in comparison to the other adolescents vaccines that were reported in the same study as being endorsed highly by these providers > 95% of the time [36].

Recognizing that providers’ HPV vaccine recommendations are often suboptimal, researchers have begun to define what components comprise “high-quality” HPV vaccine recommendations. This has been operationalized by one research group as (1) timeliness—routinely recommending the vaccine starting when the patient is ≤ 12 years; (2) consistency—recommending the vaccine for all eligible adolescents as opposed to an approach based on providers’ perception of their patients’ risk for HPV infection; (3) urgency—recommending that the vaccine be given on the same day the vaccine is being discussed, rather than offering the option of getting it at a future visit; and (4) strength—using language that clearly conveys that the provider believes the vaccine is very important for the adolescent to receive. A national study of primary care providers done in 2014 examined how frequently these quality components were implemented [37]. The results were startling and discouraging. Nearly half of providers (49%) reported they usually recommended that 11 to 12 year olds get the vaccine at a later visit, 41% used a risk-based approach for deciding when to recommend the vaccine, 27% did not tell the parents the vaccine was “very or extremely important,” and a large proportion did not start routinely recommending the vaccine before the age of 13 (39% for male patients and 25% for females) [37].

Much research has now accumulated to explain the underlying reasons why providers may not give consistent and high-quality HPV vaccine recommendations to all eligible adolescents [22]. Issues such as providers’ own knowledge about HPV-related diseases, personal beliefs about the vaccine’s safety and necessity, concern that a discussion about the vaccine will necessitate a discussion about adolescent sexuality with the parent, belief that parents will not want their child vaccinated if asked, perceptions that a provider can adequately select those patients most “in need” of HPV vaccination, and concern that raising the vaccine discussion with vaccine-hesitant parents will result in prolonged discussions have been shown to impact whether and how providers communicate about HPV vaccination during clinical visits [22,36–45]. Now that these barriers have been defined and described, there is a great need to use this knowledge to develop and evaluate interventions that help to mitigate these barriers and improve providers’ vaccine communication abilities. Such interventions are needed not only for HPV, but for all vaccines [46,47].

Possible Strategies for Helping Providers Communicate About HPV Vaccines

Before discussing these interventions, it is worth noting that several of the passive and active strategies have been shown in clinical trials to improve adolescent HPV vaccination rates. Although these are beyond the scope of this article, inclusion of these strategies should certainly be considered by any practice as a mechanism to increase vaccination levels, especially given that the most successful interventions to improve vaccination levels consist of multiple components [48]. Also useful is a recently described “taxonomy of vaccine communication interventions” that provides additional perspective on the scope and complexity of interventions to improve vaccine delivery [49]. There are several well-written review articles that describe interventions that focus on passive and active strategies at the practice or community level [50–52].

Interpersonal Communication Strategies Shown to Increase HPV Vaccination

Presumptive Communication

One of the first studies to examine the specific “way” in which providers communicate about vaccines focused not on HPV but rather on young childhood vaccines. In 2013 Opel and colleagues performed a study in which they taped clinical encounters between a pediatrician and a parent of a child aged 1 to 19 months [53]. Of the 111 encounters recorded, 50% of parents were classified as vaccine hesitant. Parents were aware they were being taped but not aware that the overall purpose of the study was to examine providers’ communication related to vaccination. The researchers found that providers generally used one of 2 communication styles to introduce the vaccine discussion. The first, called the “presumptive” style, assumed that parents would agree to vaccination and presented the vaccines as routine (ie, “We have to do some shots today”). The second style, called “participatory,” was more parent-oriented and used language suggesting shared decision-making (ie, “So what do you want to do about shots today?”). The study showed that the odds of resisting the provider’s vaccine recommendations were significantly higher when providers used a participatory approach than a presumptive one, suggesting that even small changes in language can have a major impact on the likelihood of vaccination. However, given the study design, causality between providers’ recommendation style and parents vaccination decisions could not be delineated.

In 2015 Moss and colleagues performed a study that examined the use of these 2 communication styles with regard to HPV vaccination [54]. This study used data from the 2010 National Immunization Survey–Teen, a national survey on childhood vaccination that includes provider verification of vaccines given [16]. Researchers categorized provider vaccine communication styles into “provider-driven,” which was similar to the presumptive style described Opel, and “patient-driven,” which was similar to Opel’s permissive style. Parents who received a more provider-driven style of HPV vaccine recommendation were far more likely to have allowed their adolescent to be vaccinated than those receiving patient-driven recommendations [54]. Further supporting this communication approach are results from a qualitative study done by Hughes and colleagues in which triads of mothers, adolescents, and providers were interviewed after a preventive care visit to assess the communication that occurred regarding HPV vaccination [39]. Providers’ communication style was categorized into 1 of 3 groups: paternalistic (clinician makes the vaccination decision and communicates this to the family); informed (patient and family gathers information from the clinician and other sources to reach a vaccination decision); and shared (medical and personal information is exchanged between the provider and family and then a decision is reached jointly). Providers who typically adopted the paternalistic approach perceived that they had the highest success in convincing parents to vaccinate—a perception that was confirmed in quantitative assessments of vaccination status among adolescents in the study sample [39]. Our own research demonstrates that learning and implementing a presumptive/paternalistic HPV vaccine recommendation style is easy for primary care providers to do and is perceived as often shortening the time taken during clinical visits to discuss the vaccine [55,56]. Thus, providers should consider opening the HPV vaccine conversation using this approach, and then turning to some of the other communication techniques described below when met with parental resistance or questions.

Motivational Interviewing

A second communication technique that seems effective for promoting HPV vaccination, especially for vaccine hesitant parents, is motivational interviewing. Motivational interviewing describes a communication technique in which the provider leverages a parents’ or patients’ intrinsic motivation to engage in a preferred health behavior [57]. Motivational interviewing was originally developed to combat substance abuse [58,59] but has subsequently been successfully applied to a number of other health issues [60–64]. There is growing interest from public health and medical providers in using this technique for increasing vaccination [39,65–68]. Our research group performed a large, cluster-randomized controlled trial of 16 pediatric and family medicine clinics to examine the impact of a provider communication “toolkit” on adolescent HPV vaccine series initiation and completion [50,69]. The toolkit consisted of motivational interviewing training for providers related to HPV vaccination and training on 3 tangible resources providers could also use with parents—an HPV fact sheet, an HPV vaccine decision aid, and an educational website. Results from the study demonstrated that motivational interviewing was the toolkit component most widely utilized by providers and was also perceived as being the most useful. More importantly, HPV vaccine series initiation levels were significantly higher among adolescents in practices receiving the toolkit than in control practices. There was no impact on HPV vaccine series completion (unpublished results). The usefulness of motivational interviewing for vaccination is further supported by a small study in which community pharmacists receiving motivational interviewing training for adult vaccination reported significantly higher patient readiness to receive vaccines following their interaction with the pharmacist than those who did not receive the training [70]. Finally, Perkins et al performed a cluster randomized controlled trial that evaluated the impact of a provider-focused intervention on adolescent HPV vaccination rates. The intervention included frequent provider support meetings, education on HPV infection and vaccination, feedback on providers’ individual HPV vaccination rates, provider incentives, and “basic motivational interviewing principles with vaccine-hesitant parents.” HPV vaccination series initiation and completion rates were significantly higher in intervention practices than controls, and this effect was sustained for at least 6 months after the active intervention period was over [67]. However, it was unknown how much the motivational interviewing contributed to these results. Based on the above information, and the long history of success of motivational interviewing for improving patient compliance with other recommended health behaviors, this technique appears to have a reasonable evidence base and should be considered for communicating with families that express resistance to HPV vaccination.

Personalized Communication

Parents’ reasons for not having their adolescent vaccinated against HPV are often complex and multifactorial [71,72]. Personalized approaches are needed to account for each parent’s unique informational needs, beliefs, and prior experiences [65]. Unfortunately, given the short amount of time allotted for clinical visits, it is often difficult to provide adequate information to parents during these encounters [73–75]. Indeed, concern about prolonged HPV vaccine discussions has been identified as an important barrier for providers that cause some to forgo recommending the vaccine [36,75].

One potential solution to this issue is to leverage technology in the form of web-based interventions that use software to tailor materials to each individual’s unique informational needs. Feasibility for this idea comes from the knowledge that many parents already use the web to research health issues related to their children [76], and that doctors’ offices are increasingly using patient portals and other web-based resources to help parents prepare for upcoming visits, especially those focused on health maintenance [77,78]. Tailored messaging interventions have been shown across populations and health issues to generally result in superior adherence with health behaviors when compared to untailored controls [79–82]. Several researchers have thus begun exploring whether such a personalized communication strategy may be similarly effective for adolescent HPV vaccination [50,83–85]. As an example, Maertens and colleagues used community-based participatory research techniques to develop a web-based tailored messaging intervention for Latinos regarding HPV vaccination [86]. A subsequent randomized controlled trial of the intervention in over 1200 parents of adolescents and young adults demonstrated that the intervention improved participants’ intentions to vaccinate compared to usual care [87], and among adolescents, higher HPV vaccine series initiation levels (unpublished data). Although additional work is needed to understand the feasibility of implementing such an intervention more broadly, additional support for the usefulness of a tailored messaging approach comes from a study of female university students that demonstrated higher HPV vaccination intentions after exposure to tailored information compared to untailored information. However, the impact on actual HPV vaccine utilization was not measured in the study [84]. Contrasting results were found in a different study of university students where researchers failed to find an impact of message tailoring on HPV vaccination utilization. However, this study was limited by a low response rate (~50%) to the follow up survey where vaccination status was assessed, and also by overall low levels of HPV vaccine initiation among the entire study sample (8%) [85]. Given the low number of studies in this area, and some conflicting data, additional research is needed to better understand the impact of personalized communication on HPV vaccination levels. However, results from these studies suggest that a modest benefit may be achieved with this approach, especially if coupled with other, evidence-based, clinic-level interventions to promote vaccination (eg, vaccine reminders, extended office hours), as is suggested by the Task Force on Community Preventive Services [48].

Focusing Communication on Cancer Prevention

HPV vaccines are unique in that they are only 1 of 2 vaccines for cancer prevention (the other being hepatitis B). Provider and parent surveys suggest that while most providers do mention cancer prevention when discussing HPV vaccines [40,88,89], this may be more commonly done with female patients than males [22]. Focusing on cancer prevention rather than sexual transmissibility is a communication technique suggested by the Centers for Disease Control and Prevention (CDC) as many parents cite this aspect of the vaccine as one of the most compelling reasons for vaccinating [45,90]. CDC’s “You are the Key” program [91] uses cancer prevention as a central theme in their physician and patient communication materials, based on significant prior market research on the acceptability and impact of such messages among parents and providers. In 2016 Malo and colleagues tested the potential impact of brief messages related to HPV vaccination, including cancer prevention messages, among a national sample of 776 medical providers and 1504 parents of adolescents [92]. In addition to their potential to motivate parents to vaccination, associations between parental endorsement of each message and their adolescent’s vaccination status were also examined. The cancer prevention messages were among those most highly endorsed by both parents and providers as being motivating for parents to get their adolescent vaccinated. More importantly, among parents these endorsements were associated with a significantly higher likelihood of the adolescent having been vaccinated against HPV. Interestingly, one of the briefest messages in the study, “I [the physician] strongly believe in the importance of this cancer preventing vaccine for [child’s name],” was perceived as the most persuasive message by parents.

Further support for the positive impact of framing HPV vaccines primarily as cancer prevention comes from another national study of 1495 parents of 11 to 17 year olds that examined 3 measures of quality of their adolescent provider’s HPV vaccine recommendation, and the relationship between recommendation quality and likelihood of adolescent HPV vaccination [40]. The 3 quality indicators assessed included providing information about cancer prevention, encouraging the vaccine “strongly,” and recommending it be given on the same day as it was being discussed. While 49% of parents reported receiving no HPV vaccine recommendation from their adolescents’ provider, of those that did, 86% received a cancer prevention message. Parents who had been given high quality recommendations that included either 2 or 3 of the quality indicator measures had over 9 times the odds of vaccine series initiation and 3 times the odds of vaccine series follow through than those who had not received any recommendation, and also significantly higher odds of vaccination than parents who had received low quality recommendations (ie, included only 1 indicator). Taken together, these results suggest that focusing discussions about HPV vaccines on their ability to prevent cancer is likely to be persuasive for some parents.

Strategies That Are Promising But Not Thoroughly Tested

Helping Parents Create Vaccination Plans

A recent commentary suggested that instead of focusing on changing beliefs or “educating” parents and patients about the need for a given vaccine, perhaps a better way to craft interventions for increasing vaccination is to focus on structuring the environment to make vaccination “easy” [93,94]. Examples of this include strategies such as extended office hours and making the vaccine available in other locations such as schools and pharmacies, both of which have been shown in some populations and settings to improve vaccine utilization [48,95]. One aspect of structuring a vaccine-conducive environment that relates to provider communication is helping parents create “implementation intentions” for future vaccination visits. In its most obvious form, this would mean providers provide office resources that facilitate making an appointment for the next dose in the HPV vaccine series during a clinic visit where the first dose was provided. But such an approach could also potentially extend to parents who are on the fence about the vaccine—to make an appointment before the parent leaves the office with an unvaccinated child to either re-discuss the vaccine in the future or to actually start the vaccine series. Support for such a strategy comes primarily from the social sciences, which suggest that implementation intentions work by increasing attention to specific cues to action, making it more likely that that the cue will be acted upon [96–98]. Creating implementation intentions has been shown to be helpful for improving adherence with a variety of health behaviors [99–105], and there is a growing evidence base related to how implementation intentions may facilitate vaccination specifically. For example Vet and colleagues performed a randomized controlled trial among 616 men who have sex with men with either strong or weak intentions to receive the hepatitis B vaccine [106]. Half of the participants were asked to create an implementation intention plan where they described when, where and how they would obtain the vaccine. Those in the control arm were not given this prompt. Regardless of whether their initial vaccination intention was weak or strong, those who had been asked to create an implementation plan had more than double the likelihood of actually getting the vaccine than participants who did not receive the implementation plan prompt. Similarly, a study of influenza vaccination rates among corporate employees found that those who were asked to write down the day and time they planned to go to employee health to get the free vaccine were somewhat more likely (4% higher) to be vaccinated than those who did not receive this prompt [107]. In addition, a study of elderly individuals found that influenza vaccination rates were significantly higher among those who had received “action instructions” on how, when and where to get the vaccine than those who did not [108]. These studies suggest that helping parents craft a definitive follow-up plan regarding vaccination could have a significant impact on vaccination rates—particularly for vaccines like HPV that require multiple doses.

Treating all Adolescent Vaccines the Same

Prior research has demonstrated that providers often communicate differently about HPV vaccines than other adolescent vaccines such as the tetanus-diphtheria-pertussis (Tdap) and meningococcal (MCV) vaccines [22,36]. Providers often tend to discuss the HPV vaccine last among these 3 vaccines, provide weaker endorsements of the vaccine, and pre-emptively give much more detail about the HPV compared to the other vaccines, even in the absence of a parent’s request for additional information [36,39,41]. The CDC and the American Academy of Pediatrics now suggest putting HPV at the beginning or middle of the list of vaccines recommended to the adolescent (ie, “HPV, Tdap and MCV”), and treating all recommended vaccines equivalently in terms of the level of detail provided to parents in the absence of a parent’s request for more information [109,110]. Through these suggestions have face validity, their specific impact on HPV vaccination rates, and on patient and provider satisfaction with the visit have yet to be evaluated.

Strategies that Probably Don’t Work

Presenting Myths and Facts

Research related to promoting other vaccines provides insight into communication activities that probably would not work well for promoting HPV vaccination. A 2012 study by Nyhan and colleagues examined the impact of 2 different messages related to influenza vaccines on participants’ beliefs about the vaccine’s safety and intentions to get vaccinated [111]. One group received information to correct the commonly held belief that influenza vaccine can cause the flu while the other received information about the risks associated with contracting an influenza infection. While the correction of myths did improve participants’ perceptions of the vaccine’s safety, information about influenza dangers did not. Neither message impacted intentions to vaccinate in the study subjects overall. However, in sub-analyses the correction of myths actually decreased intentions to vaccinate among those with high baseline levels of concern about the vaccine’s side effects—that is, among those most concerned that the flu vaccine can give someone the flu, correcting this myth actually decreased the likelihood that they would receive the vaccine. Similar findings have been reported in other studies related to vaccination [112–114], and suggest that the “threat” generated by providing information opposing a person’s beliefs may actually entrench these beliefs further as part of the threat response—a phenomenon known as attitude polarization [115]. These results also are consistent with the concept of negativity bias, which posits that negative information influences people’s risk perceptions more than positive information, and that the more strongly a risk is attempted to be negated, the lower the effectiveness and perceived trust of the information [116].

Using Fear Appeals

One tactic that has been suggested by some as a way to promote vaccination is to provide graphic depictions of the possible sequelae of vaccine-preventable diseases. The thought behind this idea is that because vaccination is so successful, most parents will have never experienced significant impacts from vaccine preventable diseases that, in the past, had been a major motivator for parents to vaccinate. Thus, in order to counter beliefs about “controversial” issues like vaccination, highly emotionally compelling and engaging information may be especially useful. This is a common tactic used by anti-vaccination groups to spread their own messages [117]. However, several studies suggested that using “fear appeals” (aka scare tactics) such as this to promote vaccination can actually have a negative effect on vaccination intentions. For example, in a 2011 study of a nationally representative sample of parents of children < 18 years, 4 different message formats were tested for their impact on parental intentions to vaccinate a future child with the measles-mumps-rubella vaccine (MMR) [113]. Message formats included correcting the misinformation that MMR causes autism, presenting information on MMR-related disease risk, providing a dramatic narrative about a child endangered by measles, and showing pictures of infants affected by these diseases. Counter to the study’s hypotheses, the dramatic narrative message actually increased parents’ perceptions that MMR vaccines had serious side effects, and the pictures increased parents’ belief that the MMR vaccine could cause autism. These counter-intuitive results are consistent with other studies that have examined the impact of message framing on adults’ vaccination intentions for HPV and influenza [108,118,119]. Taken together, fear appeals seem unlikely to sway many hesitant parents towards HPV vaccination.

Looking Into the Future

Moving forward, additional interventions to improve providers’ ability to communicate with families about HPV vaccination will undoubtedly be developed. A major area of interest in this regard is leveraging the power of technology and the internet, including using social media, mobile technologies, and online interventions to augment the provider/parent interaction that occurs during the clinical visit [50,120]. Web-based approaches have the benefit of generally being low cost and easy to disseminate to large populations. Such interventions have already been developed for a number of other health issues, some of which have proven effective [121,122]. However, use of the internet to promote healthy behaviors in general, and vaccination specifically, is still in its infancy. There is still much to be learned about how to create effective web-based tools, how to engage patients with them, and how to assess their impact on health outcomes [123].

Another interesting area for future research is identifying psychological “levers” to motivate parents’ vaccination intentions [94]. One example is focusing on using parents’ values (ie, protecting my child from harm) as an intervention target rather than beliefs or attitudes. This is because values tend to be inherent and static over time, compared to beliefs and attitudes, which are subject to change depending on the context [124]. Prior research has shown that interventions that leverage values rather than facts can be an effective way to overcome beliefs that are highly emotional or controversial, and that individuals are more likely to trust sources and individuals with shared values than those without [125], suggesting that this may be a useful way to motivate parents toward vaccinating their children. Self-affirmation is another example of a psychological lever that has a significant evidence base from the social science literature as a helpful tool for moving patients towards a desired health behavior [126,127], but it has not been extensively applied to the field of vaccination. Researchers in the field of vaccine delivery are increasingly recognizing the potential value of these unique intervention approaches [101,128–134], and it may be fruitful in the future to more closely examine the efficacy of interventions that target things like values, self-affirmation or other psychological levers to change parents’ HPV vaccination behaviors.

A final notable area for intervention research related to HPV vaccination is the use of video games. Although not likely to be used directly during patient visits, this strategy could be conceptualized as a potential way to augment the information conveyed to a parent by a provider directly during a clinical encounter. A meta-analysis from 2016 identified 16 different “serious” video games that were used to train and educate users about specific vaccine preventable diseases (usually influenza, none for HPV) and the need for vaccination [135]. In many of them, the objective of the game was to protect a virtual community from a vaccine preventable disease and/or manage outbreaks. Only 2 of the games evaluated outcomes in the short term (ie, at the time the game was being played). None have evaluated longer-term impacts such as vaccination intention or utilization. In the era of “plugged in” parents and adolescents, video games represent a unique but understudied mechanism for helping providers “communicate,” albeit indirectly, with families about the need for vaccination. Imagine providing a prescription to an HPV-vaccine hesitant family to “go play Zombie Wars HPV!” One would expect the curiosity factor alone would result in significant engagement with this intervention tool.

Conclusion

With persistently lagging HPV vaccination rates among U.S. adolescents, there is a growing need for effective interventions to improve adolescent HPV vaccine utilization. How providers communicate with families is one of the most influential factors in parents’ vaccination decisions. Emerging research is beginning to delineate potentially effective communication techniques such as presumptive approaches to making the vaccine recommendation, framing the vaccine as cancer preventing, and using motivational interviewing and personalized messaging when met with parental vaccine resistance. Moving forward the list of evidence-based interventions to improve providers’ HPV vaccine communication is likely to grow, and to increasingly leverage technology based solutions. However, given the complexities of the vaccination decision [136] and the ever growing spread of vaccine hesitancy [137], it is unlikely that a single intervention approach will be effective for getting adolescent HPV vaccine levels up to the national goal of 80% coverage. As has been recognized in the past, the most effective interventions for HPV vaccination in the future are likely to be multicomponent, including not only provider communication strategies but also clinic-, community-, and parent-level interventions [48].

Corresponding author: Amanda Dempsey, MD, PhD, MPH, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045, [email protected].

Financial disclosures: None reported.

Take-Home Points

• Patellofemoral disorders should be classified and diagnosed according to specific diagnostic categories (eg, lateral patellar compression syndrome) based on etiology rather than nondescriptive terminology (eg, internal derangement, patellofemoral pain syndrome).
• Patellofemoral dysplasia defines a spectrum of abnormalities ranging from the mild lateral patellar compression syndrome to the severe recurrent patellar dislocation.
• There is an inverse relationship between patient activity level and underlying patellofemoral dysplasia. This relationship determines threshold levels for each patient becoming symptomatic.
• Patients should be examined for 7 physical abnormalities, and if present, in what severity. These 7 are: vastus medialis obliquus deficiency, medial patellofemoral ligament laxity, lateral retinaculum tightness, increased quadriceps angle, hip abductor weakness, patella alta, and trochlear dysplasia.
• Advanced imaging is rarely, if ever, needed to make a diagnosis or to formulate an initial treatment plan for these common patellofemoral disorders.

To diagnose any disease or disorder implies an understanding of the condition’s cause(s), which should then lead to a logical treatment plan. For all too long, however, the diagnosis and treatment of patellofemoral disorders have been hampered by diagnoses that lack specific definitions based on etiology. A few of these are: internal derangement, chondromalacia patellae, patellar maltracking, and patellofemoral pain syndrome.

To simplify the diagnosis of patellofemoral disorders, we use a clinical classification based on etiology. This system’s defined diagnostic categories are useful in identifying probable cause(s), which can be appropriately evaluated and treated (Table).¹ In simple terms, the philosophy of this approach is to try to find out what’s wrong, and try to fix it!

This clinical classification provides a framework for common patellofemoral conditions that are more easily diagnosed, yet is intentionally incomplete omitting rare conditions (eg, tumors, metabolic bone disease, neurologic conditions).

Patellofemoral Dysplasia

Patellofemoral dysplasia (or extensor mechanism malfunction) is a cluster of physical abnormalities relating to the patellofemoral joint that vary from mild to severe and affect the normal function of that joint. As such, patellofemoral dysplasia itself should be considered on a continuum of mild to severe. To simplify the diagnosis, the clinician should systematically identify these factors and their severity. Armed with this information, the clinician can make the diagnosis and formulate a logical treatment plan for each individual patient.

This article focuses on 7 physical abnormalities that are most likely developmental and that can be identified through physical and radiologic examination. When and how each patient with patellofemoral dysplasia becomes symptomatic are determined by 2 key factors: patellofemoral dysplasia severity and activity level (sedentary to strenuous), in an inverse relationship (Figure 1).²

Seven Key Patellofemoral Physical Abnormalities

Of the 7 commonly identified physical abnormalities that affect the normal functioning of the patellofemoral joint, 5 are discovered by physical examination and 2 by radiography; CT and MRI are seldom needed in the initial evaluation. The most accurate and objective method should be used to assess the presence and severity of each abnormality.

The 7 abnormalities are vastus medialis obliquus (VMO) deficiency, medial patellofemoral ligament (MPFL) laxity, lateral retinaculum (LR) tightness, increased quadriceps (Q) angle, hip abductor weakness, patella alta, and trochlear dysplasia. We list these not in order of importance but in the order in which they are usually encountered during initial evaluation. We advocate for examining both knees including axial patellofemoral radiographs because patellofemoral disorders are frequently bilateral. It is helpful to use an abnormality checklist so none are forgotten. Also useful is a simple shorthand for findings: 0 = normal (no abnormality), 1 = mild abnormality, 2 = moderate abnormality, 3 = severe abnormality, with the right knee always recorded first (R/L). For example, severe left MPFL laxity is recorded as 0/3. Numerical values (eg, Q angles) can be directly recorded in this manner: 14°/23°.

1. Vastus Medialis Obliquus Deficiency

VMO deficiency is best seen as the sitting patient actively maintains the unsupported foot and leg at 30° knee flexion. Normally, the VMO inserts into the upper half or third of the medial edge of the patella; a deficient VMO inserts higher into the medial edge of the quadriceps tendon, or it is absent and leaves a characteristic hollow at the medial edge of the patella (Figure 2).⁴

2. Medial Patellofemoral Ligament Laxity

MPFL laxity is assessed with the lateral glide test. Again, the patient sits, but with quadriceps relaxed and foot and leg supported at 30° knee flexion. With the clinician mentally dividing the patella into vertical quadrants and pushing the patella laterally, the normal patella moves about 1 quadrant or 1 fingerbreadth. Severe MPFL laxity often elicits a positive apprehension response during the test. (Tip: Many patients are unable to relax the quadriceps while sitting; therefore, examine them supine and lift the knee into 30° flexion.) Such laxity usually means the MPFL was torn in a previous dislocation and remains elongated, leaving the patella vulnerable to repeated dislocations. The clinician should be alert to the possibility of hyperelastosis (Ehlers-Danlos syndrome) and a hyper-mobile patella. The opposite limb should be evaluated for asymmetric laxity.

3. Lateral Retinaculum Tightness

LR tightness is assessed with the medial glide test, again with the quadriceps relaxed and the knee supported at 30° flexion. With a normal LR, the patella can be pushed medially about 1 quadrant or 1 fingerbreadth. Some clinicians prefer the lateral tilt-up test, in which the lateral edge of the patella is lifted up, but this method is more difficult to quantify, is affected by the cross-sectional shape of the patella, and lacks consistency.

4. Increased Quadriceps Angle

The Q angle is one of the most important factors in the normal functioning of the patellofemoral joint. For more than a century,⁸ multiple operations have been used successfully to move the tibial tubercle (TT) and patellar ligament from a lateral position to a medial position thereby decreasing the Q angle. It is only logical to measure this angle at every knee examination to check for an abnormal increase, and the degree. The term quadriceps angle, or Q angle, was first used in 1964 by Brattström,⁷ who defined it as the “supplemental angle” to the valgus angle formed by the “quadriceps’ resultant” (line of force or vector) “+ patella + ligamentum patellae”. This might be called the dynamic Q angle. With there being no clinical method of measuring the “quadriceps line of force”, or quadriceps vector, clinicians used a line from the anterior superior iliac spine to the center of the patella, yet still called it the Q angle. By convention, this anatomical Q angle has been accepted as the Q angle.

Because the Q angle is the only clinical measurement of TT lateralization at initial evaluation, its measurement should be standardized, accurate, and simple to perform. Placing the patient supine with the lower limb in neutral rotation (patella anterior) and the knee in full extension standardizes the position. In full extension, the tibia reaches its maximum external rotation owing to the terminal “screw home” mechanism. The clinician should center the patella to the trochlear groove (TG) while measuring the Q angle, as it is the relationship of the TT to the trochlea, not to the patella, that is important. If LR tightness prevents the patella from centering, that fact should be recorded during the medial glide test for LR tightness.

5. Hip Abductor Weakness

The step-down test is easily performed in the office by having the patient stand on a short stool or stair and then slowly step down with the opposite limb to just touch the heel and slowly arise again. A positive test is indicated by the Trendelenburg sign, with the pelvis dropping down and away from the symptomatic supporting limb, the flexing knee collapsing into valgus, and the patient tending to wobble and lack stability (Figure 4).¹⁶

6. Patella Alta

Patella alta not only allows the patella to escape the confines of the trochlea earlier during active knee extension increasing the risk of patellar dislocation, but also decreases the contact footprint with the trochlea, increasing the patellofemoral joint reaction force and potentially causing patellofemoral pain and even secondary chondrosis. The simplest way to assess patellar height is with a lateral radiograph of the knee. The 3 popular methods (Insall-Salvati, Caton-Deschamps, Blackburn-Peel) all put the normal patellar height ratio at approximately 1:1, ± 20%. Berg and colleagues¹⁸ compared radiologic techniques for measuring patellar height ratio and found that Blackburn-Peel was the most accurate, reliable, and reproducible method.

7. Trochlear Dysplasia

Trochlear dysplasia, most simply a flattening of the TG, is perhaps the most important factor effecting normal patellofemoral function. However, it remains the most difficult to correctly address surgically. Senavongse and Amis¹⁹ conducted a cadaveric study demonstrating the prime importance of the TG. They found patellar stability was reduced 30% by releasing the VMO, 49% by cutting the MPFL in full knee extension, and 70% by flattening the trochlea. The most common, successful operations for correcting patellar instability depend on changing other factors that guide patellar excursion to compensate for this trochlear flattening.

The simplest way to assess trochlear dysplasia is to measure the sulcus angle on an accurate axial view radiograph of the knee at 45° flexion (Merchant view).²⁰ Dejour and colleagues²¹ popularized a technique of assessing and classifying trochlear dysplasia from a true lateral radiograph of the knee, which has the advantage of showing the trochlear at its proximal extent. Davies and colleagues²² evaluated the Dejour technique, along with patellar tilt, patellar height, and sulcus angle, to identify a rapid and reproducible radiologic feature that would indicate the need for further analysis by other imaging studies (eg, CT, MRI). They found that, if the sulcus angle was normal, analysis of other radiologic features was unlikely to reveal additional useful information. They also showed a correlation of increasing sulcus angle and severity of those other dysplasia features. Merchant and colleagues²⁰ found a mean normal sulcus angle of 138º (SD, 6º; range, 126º-150º), and Aglietti and colleagues²³ confirmed those findings with nearly identical values (mean, 137º; SD, 6º; range, 116º-151º).

Diagnosis and Initial Treatment Plan

Patellofemoral disorders generally are divided into patellofemoral pain and instability, but these 2 diagnostic categories are too broad to be useful. Patellofemoral pain is a symptom. Patellofemoral pain syndrome should never be used as a diagnosis because there is no accepted definition for the cluster of findings that customarily defines a syndrome. At initial evaluation, after the easily diagnosed causes of anterior knee pain (eg, prepatellar bursitis, TT apophysitis, patellar and quadriceps tendinitis) have been ruled out, the clinician should consider types of patellofemoral dysplasia for a presumptive diagnosis, which will then lead to a logical treatment program for each identified disorder. With a presumptive diagnosis established, almost all patients suffering from chronic anterior knee pain without history of injury are treated initially with rest, ice, and nonsteroidal anti-inflammatory drugs to restore joint homeostasis.³

Lateral Patellar Compression Syndrome

In 1975, Ficat and colleagues²⁴ described features of what they called syndrome d’hyperpression externe de la rotule. Two years later, Ficat and Hungerford²⁵ defined the syndrome as one “in which the patella is well centered in the trochlear sulcus and stable, but in which there is a functional lateralization onto a physiologically and often anatomically predominant lateral facet.” Using the tools we have described here, the clinician usually finds the cause(s) of this “functional lateralization.” Four abnormalities—VMO deficiency, LR tightness, increased standardized Q angle, and hip abductor weakness—can cause functional lateralization either alone when severe or in combination when mild or moderate.

For a presumptive diagnosis of LPCS, initial treatment is nonoperative, and successful in about 90% of patients. It should be obvious that most patients with chronic anterior knee pain have quadriceps atrophy. Physical therapy should be specifically focused on quadriceps strengthening, with absolutely no stress placed on the patellofemoral joint in flexion initially, and on hip abductor strengthening. Progressive resistive isometric quadriceps exercises can be performed with a weight-bench technique (Figures 5A-5D).²⁶

Chronic Subluxation of Patella

With the use of axial patellofemoral radiographs (Merchant views),²⁰ the clinician can determine if the “patella is well centered in the trochlear sulcus and stable” (an important part of the definition of LPCS). If the patient has no symptoms of recurrent instability or patellar dislocation, and these radiographs show a laterally subluxed patella (one not well centered in the trochlea), the diagnosis is most likely CSP, a moderate form of patellofemoral dysplasia (section II of the Table). In addition to the 4 abnormalities used in the diagnosis of LPCS (mentioned earlier), trochlear dysplasia also comes into play in the diagnosis of CSP. Just as the other abnormalities can vary from mild to severe, trochlear dysplasia can vary from mild (slightly shallow sulcus angle) to severe (flat or even convex sulcus angle). As the sulcus becomes shallower, the patella slides more laterally, increasing the likelihood of patellar dislocation.

As the patient with CSP gives no history of episodic patellar instability, treatment for CSP is almost identical to that for LPCS, with the primary focus on isometric quadriceps strengthening (DeHaven isometric exercises)²⁷ and hip abductor muscle strengthening. In the presence of CSP radiographically, it is important to use McConnell taping and/or patellar bracing during muscular strengthening. A patient who achieves 20-lb isometric quadriceps strength, demonstrates a normal step-down test, and is assumed to be asymptomatic can be allowed to return to sports activities with use of a patellar brace. The patient should be counseled that there is an increased risk for patellar dislocation because of this chronic subluxation and the shallower sulcus.

As in LPCS, CSP symptoms that persist after dynamic strength is regained may require surgical intervention. The severity of identified abnormal factors (tight LR, increased Q angle, trochlear dysplasia) guides the surgeon in selecting appropriate corrective technique(s).

Recurrent Dislocation of Patella

Admittedly, given the number and subtlety of abnormal factors, the diagnosis of LPCS as a cause of patellofemoral pain can be challenging. However, RDP is at the opposite end of the spectrum. A history of prior patellar dislocation(s) almost always makes the diagnosis of RDP easier. The patient occasionally complains of a recurrent symptom, the knee “going out” or “giving way,” indicating that the diagnosis might be RDP. By carefully asking what the patient was doing and what happened when the knee “went out”, the clinician may be able to determine if the injury stemmed from sudden patellar pain causing reflex inhibition of the quadriceps or was a true dislocation. Both may be described as “going out” or “giving way”.

Assessment for the same 7 abnormalities helps establish the diagnosis, a logical treatment plan, and a guide for indicated surgery. The diagnostic focus is MPFL laxity and trochlear dysplasia. Prior lateral dislocation of the patella almost always requires rupture of the normal MPFL. The infrequent exception is a patient with hyper-elasticity of the skin and multiple joints (Ehlers-Danlos syndrome). Trochlear dysplasia is a significant risk factor for patellar dislocation. If the trochlea is normal and there is no MPFL laxity, the diagnosis of RDP should be questioned.

If surgery is indicated, the surgeon uses a list of the patient’s abnormalities and their severity as a guide in selecting reconstructive techniques. The more abnormalities found and the greater the severity of each, the more techniques are needed to achieve success. Preoperative exercises help speed postoperative recovery by addressing quadriceps and hip abductor weakness. In addition, an active exercise program gives the surgeon insight into the patient’s desire for and commitment to recovery. Other physical abnormalities to be considered in preoperative planning include MPFL laxity, LR tightness, increased Q angle, patella alta, and trochlear dysplasia.

Surgical tips: 1. When releasing the LR, never cut the vastus lateralis tendon, as this has a high likelihood of causing iatrogenic medial patellar subluxation.²⁹ 2. When medializing the TT, consider compensating for a shallow trochlea by “over-correcting” the Q angle to 5° to 10° measured with a surgical goniometer intraoperatively.

Summary

Basing clinical classification of disorders on etiology is a simple and effective way to diagnose common patellofemoral conditions. Identifying and rating the severity of patellofemoral dysplasia, using 7 commonly found physical abnormalities, guide the physician to a proper diagnosis and down logical treatment pathways. These principles should be incorporated into the routine evaluation of patellofemoral disorders to optimize diagnosis, formulate a treatment plan, and improve patient outcomes. After all, this is what our patients are asking us to do: Try to find what’s wrong, and then try to fix it!

Am J Orthop. 2017;46(2):68-75. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Patellofemoral disorders should be classified and diagnosed according to specific diagnostic categories (eg, lateral patellar compression syndrome) based on etiology rather than nondescriptive terminology (eg, internal derangement, patellofemoral pain syndrome).
• Patellofemoral dysplasia defines a spectrum of abnormalities ranging from the mild lateral patellar compression syndrome to the severe recurrent patellar dislocation.
• There is an inverse relationship between patient activity level and underlying patellofemoral dysplasia. This relationship determines threshold levels for each patient becoming symptomatic.
• Patients should be examined for 7 physical abnormalities, and if present, in what severity. These 7 are: vastus medialis obliquus deficiency, medial patellofemoral ligament laxity, lateral retinaculum tightness, increased quadriceps angle, hip abductor weakness, patella alta, and trochlear dysplasia.
• Advanced imaging is rarely, if ever, needed to make a diagnosis or to formulate an initial treatment plan for these common patellofemoral disorders.

To diagnose any disease or disorder implies an understanding of the condition’s cause(s), which should then lead to a logical treatment plan. For all too long, however, the diagnosis and treatment of patellofemoral disorders have been hampered by diagnoses that lack specific definitions based on etiology. A few of these are: internal derangement, chondromalacia patellae, patellar maltracking, and patellofemoral pain syndrome.

To simplify the diagnosis of patellofemoral disorders, we use a clinical classification based on etiology. This system’s defined diagnostic categories are useful in identifying probable cause(s), which can be appropriately evaluated and treated (Table).¹ In simple terms, the philosophy of this approach is to try to find out what’s wrong, and try to fix it!

This clinical classification provides a framework for common patellofemoral conditions that are more easily diagnosed, yet is intentionally incomplete omitting rare conditions (eg, tumors, metabolic bone disease, neurologic conditions).

Patellofemoral Dysplasia

Patellofemoral dysplasia (or extensor mechanism malfunction) is a cluster of physical abnormalities relating to the patellofemoral joint that vary from mild to severe and affect the normal function of that joint. As such, patellofemoral dysplasia itself should be considered on a continuum of mild to severe. To simplify the diagnosis, the clinician should systematically identify these factors and their severity. Armed with this information, the clinician can make the diagnosis and formulate a logical treatment plan for each individual patient.

This article focuses on 7 physical abnormalities that are most likely developmental and that can be identified through physical and radiologic examination. When and how each patient with patellofemoral dysplasia becomes symptomatic are determined by 2 key factors: patellofemoral dysplasia severity and activity level (sedentary to strenuous), in an inverse relationship (Figure 1).²

Seven Key Patellofemoral Physical Abnormalities

Of the 7 commonly identified physical abnormalities that affect the normal functioning of the patellofemoral joint, 5 are discovered by physical examination and 2 by radiography; CT and MRI are seldom needed in the initial evaluation. The most accurate and objective method should be used to assess the presence and severity of each abnormality.

The 7 abnormalities are vastus medialis obliquus (VMO) deficiency, medial patellofemoral ligament (MPFL) laxity, lateral retinaculum (LR) tightness, increased quadriceps (Q) angle, hip abductor weakness, patella alta, and trochlear dysplasia. We list these not in order of importance but in the order in which they are usually encountered during initial evaluation. We advocate for examining both knees including axial patellofemoral radiographs because patellofemoral disorders are frequently bilateral. It is helpful to use an abnormality checklist so none are forgotten. Also useful is a simple shorthand for findings: 0 = normal (no abnormality), 1 = mild abnormality, 2 = moderate abnormality, 3 = severe abnormality, with the right knee always recorded first (R/L). For example, severe left MPFL laxity is recorded as 0/3. Numerical values (eg, Q angles) can be directly recorded in this manner: 14°/23°.

1. Vastus Medialis Obliquus Deficiency

VMO deficiency is best seen as the sitting patient actively maintains the unsupported foot and leg at 30° knee flexion. Normally, the VMO inserts into the upper half or third of the medial edge of the patella; a deficient VMO inserts higher into the medial edge of the quadriceps tendon, or it is absent and leaves a characteristic hollow at the medial edge of the patella (Figure 2).⁴

2. Medial Patellofemoral Ligament Laxity

MPFL laxity is assessed with the lateral glide test. Again, the patient sits, but with quadriceps relaxed and foot and leg supported at 30° knee flexion. With the clinician mentally dividing the patella into vertical quadrants and pushing the patella laterally, the normal patella moves about 1 quadrant or 1 fingerbreadth. Severe MPFL laxity often elicits a positive apprehension response during the test. (Tip: Many patients are unable to relax the quadriceps while sitting; therefore, examine them supine and lift the knee into 30° flexion.) Such laxity usually means the MPFL was torn in a previous dislocation and remains elongated, leaving the patella vulnerable to repeated dislocations. The clinician should be alert to the possibility of hyperelastosis (Ehlers-Danlos syndrome) and a hyper-mobile patella. The opposite limb should be evaluated for asymmetric laxity.

3. Lateral Retinaculum Tightness

LR tightness is assessed with the medial glide test, again with the quadriceps relaxed and the knee supported at 30° flexion. With a normal LR, the patella can be pushed medially about 1 quadrant or 1 fingerbreadth. Some clinicians prefer the lateral tilt-up test, in which the lateral edge of the patella is lifted up, but this method is more difficult to quantify, is affected by the cross-sectional shape of the patella, and lacks consistency.

4. Increased Quadriceps Angle

The Q angle is one of the most important factors in the normal functioning of the patellofemoral joint. For more than a century,⁸ multiple operations have been used successfully to move the tibial tubercle (TT) and patellar ligament from a lateral position to a medial position thereby decreasing the Q angle. It is only logical to measure this angle at every knee examination to check for an abnormal increase, and the degree. The term quadriceps angle, or Q angle, was first used in 1964 by Brattström,⁷ who defined it as the “supplemental angle” to the valgus angle formed by the “quadriceps’ resultant” (line of force or vector) “+ patella + ligamentum patellae”. This might be called the dynamic Q angle. With there being no clinical method of measuring the “quadriceps line of force”, or quadriceps vector, clinicians used a line from the anterior superior iliac spine to the center of the patella, yet still called it the Q angle. By convention, this anatomical Q angle has been accepted as the Q angle.

Because the Q angle is the only clinical measurement of TT lateralization at initial evaluation, its measurement should be standardized, accurate, and simple to perform. Placing the patient supine with the lower limb in neutral rotation (patella anterior) and the knee in full extension standardizes the position. In full extension, the tibia reaches its maximum external rotation owing to the terminal “screw home” mechanism. The clinician should center the patella to the trochlear groove (TG) while measuring the Q angle, as it is the relationship of the TT to the trochlea, not to the patella, that is important. If LR tightness prevents the patella from centering, that fact should be recorded during the medial glide test for LR tightness.

5. Hip Abductor Weakness

The step-down test is easily performed in the office by having the patient stand on a short stool or stair and then slowly step down with the opposite limb to just touch the heel and slowly arise again. A positive test is indicated by the Trendelenburg sign, with the pelvis dropping down and away from the symptomatic supporting limb, the flexing knee collapsing into valgus, and the patient tending to wobble and lack stability (Figure 4).¹⁶

6. Patella Alta

Patella alta not only allows the patella to escape the confines of the trochlea earlier during active knee extension increasing the risk of patellar dislocation, but also decreases the contact footprint with the trochlea, increasing the patellofemoral joint reaction force and potentially causing patellofemoral pain and even secondary chondrosis. The simplest way to assess patellar height is with a lateral radiograph of the knee. The 3 popular methods (Insall-Salvati, Caton-Deschamps, Blackburn-Peel) all put the normal patellar height ratio at approximately 1:1, ± 20%. Berg and colleagues¹⁸ compared radiologic techniques for measuring patellar height ratio and found that Blackburn-Peel was the most accurate, reliable, and reproducible method.

7. Trochlear Dysplasia

Trochlear dysplasia, most simply a flattening of the TG, is perhaps the most important factor effecting normal patellofemoral function. However, it remains the most difficult to correctly address surgically. Senavongse and Amis¹⁹ conducted a cadaveric study demonstrating the prime importance of the TG. They found patellar stability was reduced 30% by releasing the VMO, 49% by cutting the MPFL in full knee extension, and 70% by flattening the trochlea. The most common, successful operations for correcting patellar instability depend on changing other factors that guide patellar excursion to compensate for this trochlear flattening.

The simplest way to assess trochlear dysplasia is to measure the sulcus angle on an accurate axial view radiograph of the knee at 45° flexion (Merchant view).²⁰ Dejour and colleagues²¹ popularized a technique of assessing and classifying trochlear dysplasia from a true lateral radiograph of the knee, which has the advantage of showing the trochlear at its proximal extent. Davies and colleagues²² evaluated the Dejour technique, along with patellar tilt, patellar height, and sulcus angle, to identify a rapid and reproducible radiologic feature that would indicate the need for further analysis by other imaging studies (eg, CT, MRI). They found that, if the sulcus angle was normal, analysis of other radiologic features was unlikely to reveal additional useful information. They also showed a correlation of increasing sulcus angle and severity of those other dysplasia features. Merchant and colleagues²⁰ found a mean normal sulcus angle of 138º (SD, 6º; range, 126º-150º), and Aglietti and colleagues²³ confirmed those findings with nearly identical values (mean, 137º; SD, 6º; range, 116º-151º).

Diagnosis and Initial Treatment Plan

Patellofemoral disorders generally are divided into patellofemoral pain and instability, but these 2 diagnostic categories are too broad to be useful. Patellofemoral pain is a symptom. Patellofemoral pain syndrome should never be used as a diagnosis because there is no accepted definition for the cluster of findings that customarily defines a syndrome. At initial evaluation, after the easily diagnosed causes of anterior knee pain (eg, prepatellar bursitis, TT apophysitis, patellar and quadriceps tendinitis) have been ruled out, the clinician should consider types of patellofemoral dysplasia for a presumptive diagnosis, which will then lead to a logical treatment program for each identified disorder. With a presumptive diagnosis established, almost all patients suffering from chronic anterior knee pain without history of injury are treated initially with rest, ice, and nonsteroidal anti-inflammatory drugs to restore joint homeostasis.³

Lateral Patellar Compression Syndrome

In 1975, Ficat and colleagues²⁴ described features of what they called syndrome d’hyperpression externe de la rotule. Two years later, Ficat and Hungerford²⁵ defined the syndrome as one “in which the patella is well centered in the trochlear sulcus and stable, but in which there is a functional lateralization onto a physiologically and often anatomically predominant lateral facet.” Using the tools we have described here, the clinician usually finds the cause(s) of this “functional lateralization.” Four abnormalities—VMO deficiency, LR tightness, increased standardized Q angle, and hip abductor weakness—can cause functional lateralization either alone when severe or in combination when mild or moderate.

For a presumptive diagnosis of LPCS, initial treatment is nonoperative, and successful in about 90% of patients. It should be obvious that most patients with chronic anterior knee pain have quadriceps atrophy. Physical therapy should be specifically focused on quadriceps strengthening, with absolutely no stress placed on the patellofemoral joint in flexion initially, and on hip abductor strengthening. Progressive resistive isometric quadriceps exercises can be performed with a weight-bench technique (Figures 5A-5D).²⁶

Chronic Subluxation of Patella

With the use of axial patellofemoral radiographs (Merchant views),²⁰ the clinician can determine if the “patella is well centered in the trochlear sulcus and stable” (an important part of the definition of LPCS). If the patient has no symptoms of recurrent instability or patellar dislocation, and these radiographs show a laterally subluxed patella (one not well centered in the trochlea), the diagnosis is most likely CSP, a moderate form of patellofemoral dysplasia (section II of the Table). In addition to the 4 abnormalities used in the diagnosis of LPCS (mentioned earlier), trochlear dysplasia also comes into play in the diagnosis of CSP. Just as the other abnormalities can vary from mild to severe, trochlear dysplasia can vary from mild (slightly shallow sulcus angle) to severe (flat or even convex sulcus angle). As the sulcus becomes shallower, the patella slides more laterally, increasing the likelihood of patellar dislocation.

As the patient with CSP gives no history of episodic patellar instability, treatment for CSP is almost identical to that for LPCS, with the primary focus on isometric quadriceps strengthening (DeHaven isometric exercises)²⁷ and hip abductor muscle strengthening. In the presence of CSP radiographically, it is important to use McConnell taping and/or patellar bracing during muscular strengthening. A patient who achieves 20-lb isometric quadriceps strength, demonstrates a normal step-down test, and is assumed to be asymptomatic can be allowed to return to sports activities with use of a patellar brace. The patient should be counseled that there is an increased risk for patellar dislocation because of this chronic subluxation and the shallower sulcus.

As in LPCS, CSP symptoms that persist after dynamic strength is regained may require surgical intervention. The severity of identified abnormal factors (tight LR, increased Q angle, trochlear dysplasia) guides the surgeon in selecting appropriate corrective technique(s).

Recurrent Dislocation of Patella

Admittedly, given the number and subtlety of abnormal factors, the diagnosis of LPCS as a cause of patellofemoral pain can be challenging. However, RDP is at the opposite end of the spectrum. A history of prior patellar dislocation(s) almost always makes the diagnosis of RDP easier. The patient occasionally complains of a recurrent symptom, the knee “going out” or “giving way,” indicating that the diagnosis might be RDP. By carefully asking what the patient was doing and what happened when the knee “went out”, the clinician may be able to determine if the injury stemmed from sudden patellar pain causing reflex inhibition of the quadriceps or was a true dislocation. Both may be described as “going out” or “giving way”.

Assessment for the same 7 abnormalities helps establish the diagnosis, a logical treatment plan, and a guide for indicated surgery. The diagnostic focus is MPFL laxity and trochlear dysplasia. Prior lateral dislocation of the patella almost always requires rupture of the normal MPFL. The infrequent exception is a patient with hyper-elasticity of the skin and multiple joints (Ehlers-Danlos syndrome). Trochlear dysplasia is a significant risk factor for patellar dislocation. If the trochlea is normal and there is no MPFL laxity, the diagnosis of RDP should be questioned.

If surgery is indicated, the surgeon uses a list of the patient’s abnormalities and their severity as a guide in selecting reconstructive techniques. The more abnormalities found and the greater the severity of each, the more techniques are needed to achieve success. Preoperative exercises help speed postoperative recovery by addressing quadriceps and hip abductor weakness. In addition, an active exercise program gives the surgeon insight into the patient’s desire for and commitment to recovery. Other physical abnormalities to be considered in preoperative planning include MPFL laxity, LR tightness, increased Q angle, patella alta, and trochlear dysplasia.

Surgical tips: 1. When releasing the LR, never cut the vastus lateralis tendon, as this has a high likelihood of causing iatrogenic medial patellar subluxation.²⁹ 2. When medializing the TT, consider compensating for a shallow trochlea by “over-correcting” the Q angle to 5° to 10° measured with a surgical goniometer intraoperatively.

Summary

Basing clinical classification of disorders on etiology is a simple and effective way to diagnose common patellofemoral conditions. Identifying and rating the severity of patellofemoral dysplasia, using 7 commonly found physical abnormalities, guide the physician to a proper diagnosis and down logical treatment pathways. These principles should be incorporated into the routine evaluation of patellofemoral disorders to optimize diagnosis, formulate a treatment plan, and improve patient outcomes. After all, this is what our patients are asking us to do: Try to find what’s wrong, and then try to fix it!

Am J Orthop. 2017;46(2):68-75. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.