BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

[email protected]

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.

BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

[email protected]

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.

BALTIMORE – Four out of five children with asthma didn’t have access to their medication at school because the proper paperwork was missing, according to a survey of 10 inner-city Milwaukee elementary schools.

The number of students who had the required physician-signed authorization forms remained low throughout the school year, said Dr. Santiago Encalada, a pulmonary fellow at the Medical College of Wisconsin, Milwaukee.

Dr. Encalada cited administrative hurdles, lack of standardization, and challenges in school-physician-family communication as barriers to children’s access to asthma medication at school. Although school nurses in Milwaukee have standing orders for emergency albuterol administration, they otherwise need physician signatures on school-generated forms to administer both rescue and prophylactic asthma administration.

Kari Oakes/Frontline Medical News

In a study whose purpose was to assess the percentage of children with asthma who had appropriate orders on file in a sample of 10 Milwaukee inner-city schools, the schools had orders on file for just 11% of students, on average, at the beginning of the 2014-2015 school year. At the second assessment in January 2015, the average number of students with orders on file at each school had risen to 22%, with schools that had performed better earlier also showing greater gains at mid-year. However, the June 2015 assessment showed that the gains did not continue, with the schools’ aggregate average of 21% of students with appropriate orders showing no improvement from mid-year.

The number of students with asthma in schools varied from about 40 to nearly 200. Numbers varied through the school year as enrollments shifted in these high-need schools, said Dr. Encalada, who presented his findings during a poster session at the annual meeting of the Pediatric Academic Societies. In general, the schools with lower enrollments tended to do better with having orders on file, although statistical analysis was not performed for this variable.

“On average, 80% of asthmatic students in the inner city schools we studied did not have school forms or orders available for life-saving asthma rescue medications, with significant variation between schools. Our findings show that access to even basic asthma care necessities are lagging for this vulnerable population, and a significant disparity exists even within this population,” said senior author Nicholas Antos*, associate director of the Cystic Fibrosis Center at Milwaukee’s Children’s Hospital of Wisconsin.

In interviews and discussion with school nurses and physicians’ offices, Dr. Antos* and Dr. Encalada found that there were often simple but fundamental misunderstandings that impeded the proper flow of paperwork. For example, schools in Milwaukee do not have standardized forms that authorize administration of prescription medications at school, so forms may be confusing to providers and their staff. Privacy concerns sometimes impeded the ability of clinic staff to authorize treatment for students. Also, the inevitable shuffle of paperwork in school-aged families meant that the forms sometimes were simply lost on the way to school.

Understanding the barriers in the process both on the school side and in physician offices has helped Dr. Antos*, Dr. Encalada, and their colleagues to start to build a better pathway. For example, a module has been built into the EHR asthma visit template that allows easy generation of a school form and asks for patient consent for release of information to the schools.

Dr. Antos* said in an interview that the work is ongoing: “To help address these problems, we have devised interventions to improve the way school nurses can contact clinicians, and helped design innovative standardized Asthma Action Plans that can double as school orders.”

In addition to working with local providers and schools, Dr. Encalada and Dr. Antos* have reached out to pediatric societies and the American Academy of Asthma, Allergy, and Immunology (AAAAI). Emphasizing the need for “education of stakeholders of all types,” Dr. Antos* said that change “may be difficult, but we hope with the support of pediatric organizations, the AAAAI, and school administrators, we can begin to break down the barriers preventing quality and timely communication with school nurses.”

The authors had no financial disclosures. The study was funded by the Centers for Disease Control and Prevention through the Wisconsin Asthma Coalition (WAC).

[email protected]

On Twitter @karioakes

*In a previous version, Dr. Antos' name was misspelled.

The extended focused assessment with sonography for trauma (EFAST) examination provides rapid point-of-care (POC) evaluation of patients with thoracoabdominal trauma. This article offers essential clinical pearls to ensure an accurate and thorough examination, including tips on proper gain adjustment, correct probe fanning, shadow removal, visualization of the paracolic gutters, seeking the “spine sign” to determine effusion, and assessing effusion or consolidation of the lung.

Turning Down the Gain

Too much gain (signal amplification) will wash out the ultrasound image, making it challenging to detect small quantities of free fluid. This is especially true in the pelvic windows. Sound waves travel easily through the fluid-filled bladder and a posterior acoustic enhancement artifact will make the far field of the image appear too bright, obscuring small quantities of fluid (Figure 1). To correct this issue without changing the gain of the entire image, the far-field gain can be adjusted on most ultrasound devices by using the time-gain compensation bar or a far field gain knob. 

Fanning Is Key

With the probe placed at a single location on the skin, one can dramatically change the structures visualized by fanning (tilting the probe). The image visualized on the ultrasound screen represents only a single slice of the anatomy—one that is about the thickness of a credit card. A single image therefore can only show structures that are within that thin beam of the probe. Just as one would not make a clinical decision based on a single-slice computed tomography (CT) scan image, the same is true of ultrasound. By fanning the probe toward the anterior and posterior abdomen, the clinician will catch smaller quantities of free fluid within each quadrant. A good rule of thumb is to scan through the entire organ of interest from edge-to-edge (eg, the entire bladder when imaging the pelvic window; the entire kidney in the right upper quadrant (RUQ) window; the entire spleen in the left upper quadrant [LUQ]).

Get Rid of the Rib Shadows

The RUQ and LUQ windows can be difficult to visualize when the view is obscured by rib shadows. To minimize/remove rib shadows, some clinicians prefer to use the phased array probe, which has a small footprint that fits easily in the intercostal space. Clinicians who prefer using the curvilinear probe should place the probe at an oblique angle (Figure 2); this probe will fit between the ribs and remove shadowing artifacts.

Remember the Paracolic

In some patients, the paracolic gutters are the most dependent portion of the abdomen and the first place where free fluid collects. When evaluating the RUQ, the clinician should first identify Morrison’s pouch, which is the interface between the liver and the kidney. After this pouch has been identified, the clinician should slide the probe toward the patient’s feet, paying close attention to the area around the inferior tip of the liver, and continue sliding the probe down to the inferior tip of the kidney, looking for fluid layering above the kidney or the psoas muscle (Figure 3). The same holds true for the LUQ technique. Once one has looked between the spleen and the diaphragm for free fluid, the probe should be moved down to the flank to evaluate the inferior tip of the spleen and the region anterior to the kidney. 

The Left Upper Quadrant—Do Not Let the Stomach Fake You Out

A fluid-filled stomach can be a fake-out for free fluid appearing black on ultrasound (Figure 4). Remember, free fluid in the LUQ window will typically appear between the spleen and the diaphragm or at either pole of the spleen, so the clinician should pay particular attention to these areas. When evaluating the LUQ, a good rule of thumb is to place one’s hand on the patient’s bed while holding the probe; this will ensure that the scan is sufficiently posterior. The probe may also need to be fanned toward the bed to identify the kidneys in the retroperitoneum. 

Look in the Chest and Remember the Spine Sign

Rapidly identifying a hemothorax can be a critical finding on the EFAST examination. Therefore, it is important to remember that air in the lungs scatters sound waves, so one does not normally visualize distinct structures that are deep to the pleural line. This is why the spine is not typically visible in the chest above the level of the diaphragm. When pathology is present, however, the sound waves are not blocked by air-filled lungs and one can see the “spine sign,” which suggests the presence of either effusion or consolidation of the lung (Figure 5).

Tough Cardiac Window? Try These Tips

A subxiphoid window is typically used to assess for pericardial effusion. To obtain this view, the clinician usually needs to increase the depth setting by a few centimeters (typically to around 18 cm). When the patient is able to do so, he or she may assist in the examination by bending his or her knees or taking a deep breath to help bring the heart into view. Despite these efforts, however, in some patients, it is technically impossible to obtain a subxiphoid view. In such cases, switching to an alternate view, such as the parasternal window, may be successful in visualizing the subxiphoid region.

Summary

Proper gain adjustment, thorough scanning of the thoracoabdominal region, and knowledge of common artifacts and signs are essential to ensuring an accurate and thorough POC EFAST examination.

The extended focused assessment with sonography for trauma (EFAST) examination provides rapid point-of-care (POC) evaluation of patients with thoracoabdominal trauma. This article offers essential clinical pearls to ensure an accurate and thorough examination, including tips on proper gain adjustment, correct probe fanning, shadow removal, visualization of the paracolic gutters, seeking the “spine sign” to determine effusion, and assessing effusion or consolidation of the lung.

Turning Down the Gain

Too much gain (signal amplification) will wash out the ultrasound image, making it challenging to detect small quantities of free fluid. This is especially true in the pelvic windows. Sound waves travel easily through the fluid-filled bladder and a posterior acoustic enhancement artifact will make the far field of the image appear too bright, obscuring small quantities of fluid (Figure 1). To correct this issue without changing the gain of the entire image, the far-field gain can be adjusted on most ultrasound devices by using the time-gain compensation bar or a far field gain knob. 

Fanning Is Key

With the probe placed at a single location on the skin, one can dramatically change the structures visualized by fanning (tilting the probe). The image visualized on the ultrasound screen represents only a single slice of the anatomy—one that is about the thickness of a credit card. A single image therefore can only show structures that are within that thin beam of the probe. Just as one would not make a clinical decision based on a single-slice computed tomography (CT) scan image, the same is true of ultrasound. By fanning the probe toward the anterior and posterior abdomen, the clinician will catch smaller quantities of free fluid within each quadrant. A good rule of thumb is to scan through the entire organ of interest from edge-to-edge (eg, the entire bladder when imaging the pelvic window; the entire kidney in the right upper quadrant (RUQ) window; the entire spleen in the left upper quadrant [LUQ]).

Get Rid of the Rib Shadows

The RUQ and LUQ windows can be difficult to visualize when the view is obscured by rib shadows. To minimize/remove rib shadows, some clinicians prefer to use the phased array probe, which has a small footprint that fits easily in the intercostal space. Clinicians who prefer using the curvilinear probe should place the probe at an oblique angle (Figure 2); this probe will fit between the ribs and remove shadowing artifacts.

Remember the Paracolic

In some patients, the paracolic gutters are the most dependent portion of the abdomen and the first place where free fluid collects. When evaluating the RUQ, the clinician should first identify Morrison’s pouch, which is the interface between the liver and the kidney. After this pouch has been identified, the clinician should slide the probe toward the patient’s feet, paying close attention to the area around the inferior tip of the liver, and continue sliding the probe down to the inferior tip of the kidney, looking for fluid layering above the kidney or the psoas muscle (Figure 3). The same holds true for the LUQ technique. Once one has looked between the spleen and the diaphragm for free fluid, the probe should be moved down to the flank to evaluate the inferior tip of the spleen and the region anterior to the kidney. 

The Left Upper Quadrant—Do Not Let the Stomach Fake You Out

A fluid-filled stomach can be a fake-out for free fluid appearing black on ultrasound (Figure 4). Remember, free fluid in the LUQ window will typically appear between the spleen and the diaphragm or at either pole of the spleen, so the clinician should pay particular attention to these areas. When evaluating the LUQ, a good rule of thumb is to place one’s hand on the patient’s bed while holding the probe; this will ensure that the scan is sufficiently posterior. The probe may also need to be fanned toward the bed to identify the kidneys in the retroperitoneum. 

Look in the Chest and Remember the Spine Sign

Rapidly identifying a hemothorax can be a critical finding on the EFAST examination. Therefore, it is important to remember that air in the lungs scatters sound waves, so one does not normally visualize distinct structures that are deep to the pleural line. This is why the spine is not typically visible in the chest above the level of the diaphragm. When pathology is present, however, the sound waves are not blocked by air-filled lungs and one can see the “spine sign,” which suggests the presence of either effusion or consolidation of the lung (Figure 5).

Tough Cardiac Window? Try These Tips

A subxiphoid window is typically used to assess for pericardial effusion. To obtain this view, the clinician usually needs to increase the depth setting by a few centimeters (typically to around 18 cm). When the patient is able to do so, he or she may assist in the examination by bending his or her knees or taking a deep breath to help bring the heart into view. Despite these efforts, however, in some patients, it is technically impossible to obtain a subxiphoid view. In such cases, switching to an alternate view, such as the parasternal window, may be successful in visualizing the subxiphoid region.

Summary

Proper gain adjustment, thorough scanning of the thoracoabdominal region, and knowledge of common artifacts and signs are essential to ensuring an accurate and thorough POC EFAST examination.

The extended focused assessment with sonography for trauma (EFAST) examination provides rapid point-of-care (POC) evaluation of patients with thoracoabdominal trauma. This article offers essential clinical pearls to ensure an accurate and thorough examination, including tips on proper gain adjustment, correct probe fanning, shadow removal, visualization of the paracolic gutters, seeking the “spine sign” to determine effusion, and assessing effusion or consolidation of the lung.

Turning Down the Gain

Too much gain (signal amplification) will wash out the ultrasound image, making it challenging to detect small quantities of free fluid. This is especially true in the pelvic windows. Sound waves travel easily through the fluid-filled bladder and a posterior acoustic enhancement artifact will make the far field of the image appear too bright, obscuring small quantities of fluid (Figure 1). To correct this issue without changing the gain of the entire image, the far-field gain can be adjusted on most ultrasound devices by using the time-gain compensation bar or a far field gain knob. 

Fanning Is Key

With the probe placed at a single location on the skin, one can dramatically change the structures visualized by fanning (tilting the probe). The image visualized on the ultrasound screen represents only a single slice of the anatomy—one that is about the thickness of a credit card. A single image therefore can only show structures that are within that thin beam of the probe. Just as one would not make a clinical decision based on a single-slice computed tomography (CT) scan image, the same is true of ultrasound. By fanning the probe toward the anterior and posterior abdomen, the clinician will catch smaller quantities of free fluid within each quadrant. A good rule of thumb is to scan through the entire organ of interest from edge-to-edge (eg, the entire bladder when imaging the pelvic window; the entire kidney in the right upper quadrant (RUQ) window; the entire spleen in the left upper quadrant [LUQ]).

Get Rid of the Rib Shadows

The RUQ and LUQ windows can be difficult to visualize when the view is obscured by rib shadows. To minimize/remove rib shadows, some clinicians prefer to use the phased array probe, which has a small footprint that fits easily in the intercostal space. Clinicians who prefer using the curvilinear probe should place the probe at an oblique angle (Figure 2); this probe will fit between the ribs and remove shadowing artifacts.

Remember the Paracolic

In some patients, the paracolic gutters are the most dependent portion of the abdomen and the first place where free fluid collects. When evaluating the RUQ, the clinician should first identify Morrison’s pouch, which is the interface between the liver and the kidney. After this pouch has been identified, the clinician should slide the probe toward the patient’s feet, paying close attention to the area around the inferior tip of the liver, and continue sliding the probe down to the inferior tip of the kidney, looking for fluid layering above the kidney or the psoas muscle (Figure 3). The same holds true for the LUQ technique. Once one has looked between the spleen and the diaphragm for free fluid, the probe should be moved down to the flank to evaluate the inferior tip of the spleen and the region anterior to the kidney. 

The Left Upper Quadrant—Do Not Let the Stomach Fake You Out

A fluid-filled stomach can be a fake-out for free fluid appearing black on ultrasound (Figure 4). Remember, free fluid in the LUQ window will typically appear between the spleen and the diaphragm or at either pole of the spleen, so the clinician should pay particular attention to these areas. When evaluating the LUQ, a good rule of thumb is to place one’s hand on the patient’s bed while holding the probe; this will ensure that the scan is sufficiently posterior. The probe may also need to be fanned toward the bed to identify the kidneys in the retroperitoneum. 

Look in the Chest and Remember the Spine Sign

Rapidly identifying a hemothorax can be a critical finding on the EFAST examination. Therefore, it is important to remember that air in the lungs scatters sound waves, so one does not normally visualize distinct structures that are deep to the pleural line. This is why the spine is not typically visible in the chest above the level of the diaphragm. When pathology is present, however, the sound waves are not blocked by air-filled lungs and one can see the “spine sign,” which suggests the presence of either effusion or consolidation of the lung (Figure 5).

Tough Cardiac Window? Try These Tips

A subxiphoid window is typically used to assess for pericardial effusion. To obtain this view, the clinician usually needs to increase the depth setting by a few centimeters (typically to around 18 cm). When the patient is able to do so, he or she may assist in the examination by bending his or her knees or taking a deep breath to help bring the heart into view. Despite these efforts, however, in some patients, it is technically impossible to obtain a subxiphoid view. In such cases, switching to an alternate view, such as the parasternal window, may be successful in visualizing the subxiphoid region.

Summary

Proper gain adjustment, thorough scanning of the thoracoabdominal region, and knowledge of common artifacts and signs are essential to ensuring an accurate and thorough POC EFAST examination.

Case

An otherwise healthy 29-year-old man presented to the ED for evaluation of right arm pain. He had been throwing a baseball when he felt acute onset of severe pain in his right shoulder and became unable to use his arm. Radiographs of the humerus were obtained (Figure a and b).

Fracture of the Humerus

A thrower’s fracture is a rare fracture pattern characterized by a spontaneous fracture of the mid to distal third of the humeral diaphysis during an attempted throwing motion. It was first described by Wilmoth in a case report published in 1930.¹ Understanding the proposed mechanism and complications of injury are important for proper work-up and management in the ED.

Fractures of the humerus in young adults are typically the result of high-energy direct trauma. So how does the humerus fracture from throwing a baseball? The most commonly proposed mechanism is an excessive torque during the cocking and acceleration phases of the throwing motion.^2-5 This can be visualized as a pitcher’s arm maximally cocked back prior to forward acceleration. During the transition into the acceleration phase, internal rotation is abruptly initiated by the subscapularis, pectoralis major, and latissimus dorsi.^6,7 The distal humerus continues to externally rotate due to the momentum generated by the cocking phase, while the proximal humerus violently internally rotates, creating a torsional force on the humerus at the insertion of these muscles and a fulcrum for potential fracture.⁸ Spiral fractures are the most commonly seen fracture pattern, which correlates with this proposed mechanism.⁹

Thrower’s fractures are most commonly reported in men in their 20s and 30s who are less seasoned athletes.^10,11 These individuals are potentially at greater risk due to the lack of compensatory humeral cortical hypertrophy from repetitive throwing^10,12  coupled with a less refined throwing motion.¹³ Additionally, up to 75% of patients experience prodromal throwing pain at the impending fracture site,¹¹ which suggests that a primary insult such as a stress fracture may also predispose patients to this fracture pattern.

Once a fracture is suspected, a neurovascular assessment should immediately be performed, because concurrent radial nerve injuries have been reported in an average of 11.8% of mid-distal humeral fractures.¹⁴ Fractures with associated radial nerve deficits should not be reduced without an orthopedic consultation. Most radial nerve injuries are the result of neuropraxia, which usually resolves spontaneously, and attempted reduction may result in worsening nerve damage.^14,15 Additionally, the orthopedist may consider late exploration if no spontaneous nerve recovery occurs within 3 to 6 months.¹⁶ Thrower’s fractures with or without associated radial nerve palsies are typically treated conservatively with a hanging cast, which has shown similar results to orthopedic fixation.^10,17 The emergency physician should feel comfortable not ordering additional imaging to search for a pathological fracture, unless plain films suggest otherwise.

Case

An otherwise healthy 29-year-old man presented to the ED for evaluation of right arm pain. He had been throwing a baseball when he felt acute onset of severe pain in his right shoulder and became unable to use his arm. Radiographs of the humerus were obtained (Figure a and b).

Fracture of the Humerus

A thrower’s fracture is a rare fracture pattern characterized by a spontaneous fracture of the mid to distal third of the humeral diaphysis during an attempted throwing motion. It was first described by Wilmoth in a case report published in 1930.¹ Understanding the proposed mechanism and complications of injury are important for proper work-up and management in the ED.

Fractures of the humerus in young adults are typically the result of high-energy direct trauma. So how does the humerus fracture from throwing a baseball? The most commonly proposed mechanism is an excessive torque during the cocking and acceleration phases of the throwing motion.^2-5 This can be visualized as a pitcher’s arm maximally cocked back prior to forward acceleration. During the transition into the acceleration phase, internal rotation is abruptly initiated by the subscapularis, pectoralis major, and latissimus dorsi.^6,7 The distal humerus continues to externally rotate due to the momentum generated by the cocking phase, while the proximal humerus violently internally rotates, creating a torsional force on the humerus at the insertion of these muscles and a fulcrum for potential fracture.⁸ Spiral fractures are the most commonly seen fracture pattern, which correlates with this proposed mechanism.⁹

Thrower’s fractures are most commonly reported in men in their 20s and 30s who are less seasoned athletes.^10,11 These individuals are potentially at greater risk due to the lack of compensatory humeral cortical hypertrophy from repetitive throwing^10,12  coupled with a less refined throwing motion.¹³ Additionally, up to 75% of patients experience prodromal throwing pain at the impending fracture site,¹¹ which suggests that a primary insult such as a stress fracture may also predispose patients to this fracture pattern.

Once a fracture is suspected, a neurovascular assessment should immediately be performed, because concurrent radial nerve injuries have been reported in an average of 11.8% of mid-distal humeral fractures.¹⁴ Fractures with associated radial nerve deficits should not be reduced without an orthopedic consultation. Most radial nerve injuries are the result of neuropraxia, which usually resolves spontaneously, and attempted reduction may result in worsening nerve damage.^14,15 Additionally, the orthopedist may consider late exploration if no spontaneous nerve recovery occurs within 3 to 6 months.¹⁶ Thrower’s fractures with or without associated radial nerve palsies are typically treated conservatively with a hanging cast, which has shown similar results to orthopedic fixation.^10,17 The emergency physician should feel comfortable not ordering additional imaging to search for a pathological fracture, unless plain films suggest otherwise.

Case

An otherwise healthy 29-year-old man presented to the ED for evaluation of right arm pain. He had been throwing a baseball when he felt acute onset of severe pain in his right shoulder and became unable to use his arm. Radiographs of the humerus were obtained (Figure a and b).

Fracture of the Humerus

A thrower’s fracture is a rare fracture pattern characterized by a spontaneous fracture of the mid to distal third of the humeral diaphysis during an attempted throwing motion. It was first described by Wilmoth in a case report published in 1930.¹ Understanding the proposed mechanism and complications of injury are important for proper work-up and management in the ED.

Fractures of the humerus in young adults are typically the result of high-energy direct trauma. So how does the humerus fracture from throwing a baseball? The most commonly proposed mechanism is an excessive torque during the cocking and acceleration phases of the throwing motion.^2-5 This can be visualized as a pitcher’s arm maximally cocked back prior to forward acceleration. During the transition into the acceleration phase, internal rotation is abruptly initiated by the subscapularis, pectoralis major, and latissimus dorsi.^6,7 The distal humerus continues to externally rotate due to the momentum generated by the cocking phase, while the proximal humerus violently internally rotates, creating a torsional force on the humerus at the insertion of these muscles and a fulcrum for potential fracture.⁸ Spiral fractures are the most commonly seen fracture pattern, which correlates with this proposed mechanism.⁹

Thrower’s fractures are most commonly reported in men in their 20s and 30s who are less seasoned athletes.^10,11 These individuals are potentially at greater risk due to the lack of compensatory humeral cortical hypertrophy from repetitive throwing^10,12  coupled with a less refined throwing motion.¹³ Additionally, up to 75% of patients experience prodromal throwing pain at the impending fracture site,¹¹ which suggests that a primary insult such as a stress fracture may also predispose patients to this fracture pattern.

Once a fracture is suspected, a neurovascular assessment should immediately be performed, because concurrent radial nerve injuries have been reported in an average of 11.8% of mid-distal humeral fractures.¹⁴ Fractures with associated radial nerve deficits should not be reduced without an orthopedic consultation. Most radial nerve injuries are the result of neuropraxia, which usually resolves spontaneously, and attempted reduction may result in worsening nerve damage.^14,15 Additionally, the orthopedist may consider late exploration if no spontaneous nerve recovery occurs within 3 to 6 months.¹⁶ Thrower’s fractures with or without associated radial nerve palsies are typically treated conservatively with a hanging cast, which has shown similar results to orthopedic fixation.^10,17 The emergency physician should feel comfortable not ordering additional imaging to search for a pathological fracture, unless plain films suggest otherwise.

Fifty-year-old twin sisters are seen for what appears to be the same problem: changes in the color and texture of their neck skin, recently noted by a family member. Both deny ever noticing it before and further deny experiencing any associated symptoms.

The sisters are accompanying their mother, who is being treated for basal cell carcinoma. All three women grew up living and working on the family farm, spending a great deal of time in the sun from an early age.

EXAMINATION
Both patients have type III skin, meaning that they seldom burn, tan fairly easily, and are able to keep that tan. The patients have identical, obvious hypo- and hyperpigmentation covering the sides of their faces and necks, sparing a well-defined oval area on the submental anterior neck.

The affected areas appear hyperemic, displaying a reddish brown tinge, but fail to blanch with digital pressure. The changes are completely macular.

What is the diagnosis?

DISCUSSION
The changes seen with poikiloderma of Civatte (PC) are obvious to the observer (see photograph) but appear so gradually that the patient often fails to notice them until they are pointed out. Both patients in this case almost certainly have had the condition for years.

PC was first described by Achille Civatte in France in 1923, around the same time that sunbathing became popular. Prior to that time, most women carefully protected their skin from the sun.

Civatte and others found that virtually all PC patients had a history of chronic overexposure to the sun, and that the clinical features of the condition—especially the characteristic sparing of the anterior neck skin (due to shading by the chin)—supported this hypothesis. They were also able to detect histologic changes (eg, solar elastosis) on biopsy, which further corroborated this theory.

There is little doubt that chronic overexposure to UV radiation is the cause, though other factors appear to be involved, as this case illustrates. For example, PC affects far more women than men, which suggests a possible role for hormones. It also appears that, in some cases, the tendency to develop PC is due to the genetic inheritance of an increased susceptibility to UV light. The mother of the two women in this case also had PC.

The range of presentations of PC includes involvement of the chest, face, and posterior neck. It should also be noted that somewhat similar patterns can be seen in other diseases, such as lupus, dermatomyositis, and early cutaneous T-cell lymphoma. Careful history-taking and biopsy, when indicated, will serve to distinguish between these diagnoses.

PC is usually left untreated, although lasers have been successfully used on motivated patients.

TAKE-HOME LEARNING POINTS
• Poikiloderma of Civatte (PC) is quite common and is seen more in women than men.

• Chronic overexposure to UV light is the primary cause of PC, but other factors—such as gender and heredity—appear to be involved.

• The term poikiloderma refers to the variability of the red, brown, and white color changes, as well as the solar atrophy seen with this condition.

• The differential for PC includes lupus, dermatomyositis, and early cutaneous T-cell lymphoma.

Fifty-year-old twin sisters are seen for what appears to be the same problem: changes in the color and texture of their neck skin, recently noted by a family member. Both deny ever noticing it before and further deny experiencing any associated symptoms.

The sisters are accompanying their mother, who is being treated for basal cell carcinoma. All three women grew up living and working on the family farm, spending a great deal of time in the sun from an early age.

EXAMINATION
Both patients have type III skin, meaning that they seldom burn, tan fairly easily, and are able to keep that tan. The patients have identical, obvious hypo- and hyperpigmentation covering the sides of their faces and necks, sparing a well-defined oval area on the submental anterior neck.

The affected areas appear hyperemic, displaying a reddish brown tinge, but fail to blanch with digital pressure. The changes are completely macular.

What is the diagnosis?

DISCUSSION
The changes seen with poikiloderma of Civatte (PC) are obvious to the observer (see photograph) but appear so gradually that the patient often fails to notice them until they are pointed out. Both patients in this case almost certainly have had the condition for years.

PC was first described by Achille Civatte in France in 1923, around the same time that sunbathing became popular. Prior to that time, most women carefully protected their skin from the sun.

Civatte and others found that virtually all PC patients had a history of chronic overexposure to the sun, and that the clinical features of the condition—especially the characteristic sparing of the anterior neck skin (due to shading by the chin)—supported this hypothesis. They were also able to detect histologic changes (eg, solar elastosis) on biopsy, which further corroborated this theory.

There is little doubt that chronic overexposure to UV radiation is the cause, though other factors appear to be involved, as this case illustrates. For example, PC affects far more women than men, which suggests a possible role for hormones. It also appears that, in some cases, the tendency to develop PC is due to the genetic inheritance of an increased susceptibility to UV light. The mother of the two women in this case also had PC.

The range of presentations of PC includes involvement of the chest, face, and posterior neck. It should also be noted that somewhat similar patterns can be seen in other diseases, such as lupus, dermatomyositis, and early cutaneous T-cell lymphoma. Careful history-taking and biopsy, when indicated, will serve to distinguish between these diagnoses.

PC is usually left untreated, although lasers have been successfully used on motivated patients.

TAKE-HOME LEARNING POINTS
• Poikiloderma of Civatte (PC) is quite common and is seen more in women than men.

• Chronic overexposure to UV light is the primary cause of PC, but other factors—such as gender and heredity—appear to be involved.

• The term poikiloderma refers to the variability of the red, brown, and white color changes, as well as the solar atrophy seen with this condition.

• The differential for PC includes lupus, dermatomyositis, and early cutaneous T-cell lymphoma.

Fifty-year-old twin sisters are seen for what appears to be the same problem: changes in the color and texture of their neck skin, recently noted by a family member. Both deny ever noticing it before and further deny experiencing any associated symptoms.

The sisters are accompanying their mother, who is being treated for basal cell carcinoma. All three women grew up living and working on the family farm, spending a great deal of time in the sun from an early age.

EXAMINATION
Both patients have type III skin, meaning that they seldom burn, tan fairly easily, and are able to keep that tan. The patients have identical, obvious hypo- and hyperpigmentation covering the sides of their faces and necks, sparing a well-defined oval area on the submental anterior neck.

The affected areas appear hyperemic, displaying a reddish brown tinge, but fail to blanch with digital pressure. The changes are completely macular.

What is the diagnosis?

DISCUSSION
The changes seen with poikiloderma of Civatte (PC) are obvious to the observer (see photograph) but appear so gradually that the patient often fails to notice them until they are pointed out. Both patients in this case almost certainly have had the condition for years.

PC was first described by Achille Civatte in France in 1923, around the same time that sunbathing became popular. Prior to that time, most women carefully protected their skin from the sun.

Civatte and others found that virtually all PC patients had a history of chronic overexposure to the sun, and that the clinical features of the condition—especially the characteristic sparing of the anterior neck skin (due to shading by the chin)—supported this hypothesis. They were also able to detect histologic changes (eg, solar elastosis) on biopsy, which further corroborated this theory.

There is little doubt that chronic overexposure to UV radiation is the cause, though other factors appear to be involved, as this case illustrates. For example, PC affects far more women than men, which suggests a possible role for hormones. It also appears that, in some cases, the tendency to develop PC is due to the genetic inheritance of an increased susceptibility to UV light. The mother of the two women in this case also had PC.

The range of presentations of PC includes involvement of the chest, face, and posterior neck. It should also be noted that somewhat similar patterns can be seen in other diseases, such as lupus, dermatomyositis, and early cutaneous T-cell lymphoma. Careful history-taking and biopsy, when indicated, will serve to distinguish between these diagnoses.

PC is usually left untreated, although lasers have been successfully used on motivated patients.

TAKE-HOME LEARNING POINTS
• Poikiloderma of Civatte (PC) is quite common and is seen more in women than men.

• Chronic overexposure to UV light is the primary cause of PC, but other factors—such as gender and heredity—appear to be involved.

• The term poikiloderma refers to the variability of the red, brown, and white color changes, as well as the solar atrophy seen with this condition.

• The differential for PC includes lupus, dermatomyositis, and early cutaneous T-cell lymphoma.

Too Much Medication, Too Little Monitoring

A 58-year-old man presented to the ED via emergency medical services (EMS) for evaluation of severe low-back pain. The patient said the pain started abruptly, approximately 1 hour earlier when he was picking up a 50-lb television set. He stated that the pain was so severe that he was unable to move and was forced to lie down on the floor. Although the patient noted that he had a history of a “bad back,” he said he never required surgery and never experienced an episode this severe. The patient denied any radiation of pain or lower extremity numbness or weakness. He denied any chest pain or abdominal pain. His medical history was significant for obstructive sleep apnea and hypertension for which he was taking hydrochlorothiazide. Regarding his social history, he denied any tobacco or alcohol use.

Upon presentation, the patient was found to be in extreme discomfort, rating his pain as an “11” on a scale of 0 to 10. His vital signs were heart rate (HR), 110 beats/minute; blood pressure (BP), 154/91 mm Hg; respiratory rate, 20 breaths/minute; and temperature, 98.6°F. Oxygen (O₂) saturation was 98% on room air.

When the emergency physician (EP) entered the examination room, the patient was in bed, resting on his side and moaning from the pain. The head, eyes, ears, nose, and throat, cardiac, and lung examinations were all normal. The patient’s abdomen was soft and nontender and without guarding, rebound, or palpable mass. When the EP examined the patient’s back, there was no midline tenderness over the thoracic and lumbar spine. The patient did, however, exhibit bilateral paraspinal lumbar muscle tenderness to palpation and muscle spasm. After much prompting, he demonstrated 5/5 motor strength in his lower extremities bilaterally. The dorsalis pedis and posterior tibial pulses were 2+ and symmetrical.

To treat the patient’s severe pain, the EP had a saline lock placed and ordered intravenous (IV) hydromorphone 1 mg, ondansetron 4 mg, and diazepam 5 mg. No laboratory or imaging studies were ordered. Ninety minutes after receiving the analgesics, the patient continued to complain of severe pain without any improvement, and the EP ordered another two rounds of IV hydromorphone 1 mg and diazepam 5 mg. The EP did not return to check up on the patient, but rather relied solely on updates from the patient’s nurse.

Despite the additional doses of hydromorphone and diazepam, the patient continued to complain of severe pain, and the EP ordered IV hydromorphone 2 mg and diazepam 10 mg. Shortly after the patient received this third round of analgesics, his wife arrived at the ED asking to see her husband. When she entered his room, the patient was unresponsive. A code was called and the patient was found to be in asystole. Despite aggressive resuscitative efforts that included intubation, cardiopulmonary resuscitation, and advanced cardiac life support medications, the patient did not recover.

The patient’s wife sued the EP, the ED nurse, and the hospital for failure to appropriately monitor her husband while he received multiple doses of analgesic and sedative agents. The plaintiff argued that the patient’s death was caused by a cardiac arrest occurring secondary to a respiratory arrest, and that the respiratory arrest was secondary to the medications he was given in the ED. The defendants denied the allegations. A $2 million settlement was reached prior to trial.

Discussion

This was clearly a preventable death. Emergency physicians treat pain daily and should be knowledgeable about and experienced in managing acute pain. When evaluating and treating a patient’s pain, the EP must select the appropriate medication. Though we often talk about a tiered approach to pain in the ED, most of us would agree that opioids, usually via IV, are the first choice for managing severe pain.

In addition to prescribing the appropriate analgesics, the EP must identify which patients are at risk of opioid complications. This patient was at risk for opioid-induced respiratory depression based on his age (ie, >55 years old) and history of obstructive sleep apnea. These two risk factors, along with pre-existing chronic obstructive pulmonary disease, anatomic oral or airway abnormalities, and comorbidities (eg, renal or hepatic impairment), place patients at high risk for opioid-associated complications.¹ Patients with any of these conditions must be closely monitored and, based on their response to the prescribed analgesia, the EP may need to decrease the analgesic dosage and increase dosage intervals. In addition to close monitoring, reversal agents such as naloxone should be readily available in case of respiratory depression.

The problem in this case was not the selection of hydromorphone as the initial analgesic agent. Hydromorphone is frequently used safely in the ED to treat severe pain associated with conditions such as sickle cell vaso-occlusive pain crisis, renal colic, and long-bone fracture. Issues arise when hydromorphone is combined with a benzodiazepine (in this case, diazepam), which by itself causes sedation and anxiolysis. Central nervous system (CNS) depression may be additive and occur when benzodiazepines are used concomitantly with drugs that also cause CNS depression (eg, opioids).¹ This combination can lead to excessive sedation, resulting in partial airway obstruction and hypoxia.¹ For example, in an investigation by Bailey et al,² in human volunteers, neither hypoxemia nor apnea was evident after administration of .05 mg/kg of IV midazolam. In patients who received 2 mcg/kg of IV fentanyl alone, hypoxemia occurred in 50%, but apnea did not occur in any of the patients studied. However, when the same doses of these drugs were administered together, 92% of participants exhibited hypoxemia and 50% became apneic.²

When a combination of an opioid and benzodiazepine are given over frequent intervals, the clinician crosses over from treating pain to performing procedural sedation and analgesia—whether he intended to or not. As such, the patient in this case required proper monitoring, including cardiac monitoring and pulse oximetry; he also should have been placed on supplemental O₂. Ideally, the patient would have benefited from end-tidal carbon dioxide (ETCO₂), monitoring, if available. This is a noninvasive measurement of the partial pressure of CO₂ in exhaled breath. Hypoventilation from respiratory depression results in an increase in ETCO₂, and hyperventilation results in a decreased ETCO₂. While pulse oximetry is excellent at monitoring O₂ saturation, it is ineffective in the early detection of respiratory depression, hypoventilation, and apnea. The hypercarbia precedes the hypoxemia—by as much as 60 seconds (range 5-240 seconds), according to a study by Deitch et al.³

Finally, rather than relying solely on the reports from the nurse, the EP should have personally reassessed the patient at some point. Nursing updates are extremely helpful, but when ordering repeated doses of IV opioids and benzodiazepines, the EP should personally reassess the patient.
 

Hot Red Knee

 64-year-old man presented to the ED with a chief complaint of right knee pain, which he stated began approximately 2 days earlier. He denied any injury or trauma or a recent history of fever, chills, or other joint complaints. He described the pain as constant, worse with weight bearing, and becoming progressively more painful. The patient had a history of gout; however, previous attacks had only affected his great toes and elbows. His medical history was also significant for hypertension, for which he was taking lisinopril and hydrochlorothiazide. He admitted to moderate alcohol consumption but denied tobacco use.

On physical examination, the patient appeared uncomfortable due to the knee pain. All of his vital signs were normal. A focused examination of the affected knee revealed a small effusion, diffuse tenderness to palpation, mild erythema, and slight increased warmth. The patient exhibited pain with flexion and extension of the right knee. The right ankle examination and right dorsalis pedis pulse and posterior tibial pulse were all normal. No laboratory or imaging studies were obtained.

Based on the patient’s history and physical examination, the EP believed the patient’s symptoms were due to an episode of gout. He prescribed oral colchicine, allopurinol, and acetaminophen/hydrocodone; he also advised the patient to apply warm compresses to the affected area and limit his activity. He discharged the patient home with instructions to follow up with his primary care physician.

Two days after discharge, the patient returned to the same ED via EMS. On this presentation, he was febrile, with a temperature of 102.6^oF; a HR of 120 beats/minute; and a BP of 92/50 mm Hg. He also had altered mental status. The patient’s right knee appeared more swollen, and he would not flex it due to the severe pain. The EP was concerned for sepsis, and ordered blood cultures, a complete blood count, basic metabolic profile, and lactic acid evaluation. The patient was administered 2 L normal saline IV and broad-spectrum antibiotics. Despite the addition of vasopressors, he continued to deteriorate; he ultimately went into cardiac arrest and died.

The patient’s family sued the EP from the initial ED visit for failure to diagnose the right knee pain and swelling as septic arthritis (SA). The plaintiff’s attorney argued that this failure to diagnosis directly caused the patient’s sepsis and death. The EP argued that the patient’s history and physical examination were consistent with an acute gout attack, that there was no evidence of infection in the right knee, and that this was not the cause of the patient’s death. At trial, the jury returned a verdict in favor of the defense.

Discussion

Gout is caused by the precipitation of uric acid crystals into a joint. Attacks are usually monoarticular as opposed to polyarticular. The presence of hyperuricemia is variable; some patients have high serum uric acid levels and never experience gout, while other patients have normal serum uric acid levels and experience gout attacks. The condition is more common in men than in women. There are multiple risk factors for the development of gout, including obesity, hypertension, chronic kidney disease, regular excessive consumption of alcohol, taking diuretics, and consuming foods high in fructose corn syrup.¹ The joints most often affected are the great toe and knee. Patients with gout typically complain of pain, swelling, redness, and increased warmth in the affected area.

Unfortunately, the clinical presentation of an acute gout attack and SA are indistinguishable.² Risk factors for SA include IV drug abuse, diabetes mellitus, having a prosthetic joint, immunosuppression, and human immunodeficiency virus infection. The only reliable way to distinguish between gout and SA requires arthrocentesis with microscopic examination of the synovial fluid for bacteria, crystals, white blood cell (WBC) count, and culture.²

It is critical not to miss SA because it is associated with significant morbidity and a mortality rate of 11%.² To further complicate the diagnosis, some patients can experience SA in the setting of an acute gout attack. In a study of all joint aspirations with crystals (both uric acid and calcium pyrophosphate), there was a 5.2% incidence of concomitant infection.² Similarly, in patients with confirmed SA, crystals were present 21% of the time.²

A gram stain of the synovial fluid is highly specific, but only positive in 59% of cases of SA. Therefore, a negative gram stain does not exclude the diagnosis. Similarly, the presence of crystals does not exclude a coexisting joint infection. If there is high clinical suspicion for SA or an elevated synovial WBC, the patient should be presumed to have SA and treated as such until cultures prove otherwise.

It is unclear if this patient had SA. However, an EP is taking a risk in diagnosing an acute gout attack based solely on a patient’s history and physical examination. The EP should always be mindful that gout and SA can present with the identical signs and symptoms, and can present concomitantly.

Too Much Medication, Too Little Monitoring

A 58-year-old man presented to the ED via emergency medical services (EMS) for evaluation of severe low-back pain. The patient said the pain started abruptly, approximately 1 hour earlier when he was picking up a 50-lb television set. He stated that the pain was so severe that he was unable to move and was forced to lie down on the floor. Although the patient noted that he had a history of a “bad back,” he said he never required surgery and never experienced an episode this severe. The patient denied any radiation of pain or lower extremity numbness or weakness. He denied any chest pain or abdominal pain. His medical history was significant for obstructive sleep apnea and hypertension for which he was taking hydrochlorothiazide. Regarding his social history, he denied any tobacco or alcohol use.

Upon presentation, the patient was found to be in extreme discomfort, rating his pain as an “11” on a scale of 0 to 10. His vital signs were heart rate (HR), 110 beats/minute; blood pressure (BP), 154/91 mm Hg; respiratory rate, 20 breaths/minute; and temperature, 98.6°F. Oxygen (O₂) saturation was 98% on room air.

When the emergency physician (EP) entered the examination room, the patient was in bed, resting on his side and moaning from the pain. The head, eyes, ears, nose, and throat, cardiac, and lung examinations were all normal. The patient’s abdomen was soft and nontender and without guarding, rebound, or palpable mass. When the EP examined the patient’s back, there was no midline tenderness over the thoracic and lumbar spine. The patient did, however, exhibit bilateral paraspinal lumbar muscle tenderness to palpation and muscle spasm. After much prompting, he demonstrated 5/5 motor strength in his lower extremities bilaterally. The dorsalis pedis and posterior tibial pulses were 2+ and symmetrical.

To treat the patient’s severe pain, the EP had a saline lock placed and ordered intravenous (IV) hydromorphone 1 mg, ondansetron 4 mg, and diazepam 5 mg. No laboratory or imaging studies were ordered. Ninety minutes after receiving the analgesics, the patient continued to complain of severe pain without any improvement, and the EP ordered another two rounds of IV hydromorphone 1 mg and diazepam 5 mg. The EP did not return to check up on the patient, but rather relied solely on updates from the patient’s nurse.

Despite the additional doses of hydromorphone and diazepam, the patient continued to complain of severe pain, and the EP ordered IV hydromorphone 2 mg and diazepam 10 mg. Shortly after the patient received this third round of analgesics, his wife arrived at the ED asking to see her husband. When she entered his room, the patient was unresponsive. A code was called and the patient was found to be in asystole. Despite aggressive resuscitative efforts that included intubation, cardiopulmonary resuscitation, and advanced cardiac life support medications, the patient did not recover.

The patient’s wife sued the EP, the ED nurse, and the hospital for failure to appropriately monitor her husband while he received multiple doses of analgesic and sedative agents. The plaintiff argued that the patient’s death was caused by a cardiac arrest occurring secondary to a respiratory arrest, and that the respiratory arrest was secondary to the medications he was given in the ED. The defendants denied the allegations. A $2 million settlement was reached prior to trial.

Discussion

This was clearly a preventable death. Emergency physicians treat pain daily and should be knowledgeable about and experienced in managing acute pain. When evaluating and treating a patient’s pain, the EP must select the appropriate medication. Though we often talk about a tiered approach to pain in the ED, most of us would agree that opioids, usually via IV, are the first choice for managing severe pain.

In addition to prescribing the appropriate analgesics, the EP must identify which patients are at risk of opioid complications. This patient was at risk for opioid-induced respiratory depression based on his age (ie, >55 years old) and history of obstructive sleep apnea. These two risk factors, along with pre-existing chronic obstructive pulmonary disease, anatomic oral or airway abnormalities, and comorbidities (eg, renal or hepatic impairment), place patients at high risk for opioid-associated complications.¹ Patients with any of these conditions must be closely monitored and, based on their response to the prescribed analgesia, the EP may need to decrease the analgesic dosage and increase dosage intervals. In addition to close monitoring, reversal agents such as naloxone should be readily available in case of respiratory depression.

The problem in this case was not the selection of hydromorphone as the initial analgesic agent. Hydromorphone is frequently used safely in the ED to treat severe pain associated with conditions such as sickle cell vaso-occlusive pain crisis, renal colic, and long-bone fracture. Issues arise when hydromorphone is combined with a benzodiazepine (in this case, diazepam), which by itself causes sedation and anxiolysis. Central nervous system (CNS) depression may be additive and occur when benzodiazepines are used concomitantly with drugs that also cause CNS depression (eg, opioids).¹ This combination can lead to excessive sedation, resulting in partial airway obstruction and hypoxia.¹ For example, in an investigation by Bailey et al,² in human volunteers, neither hypoxemia nor apnea was evident after administration of .05 mg/kg of IV midazolam. In patients who received 2 mcg/kg of IV fentanyl alone, hypoxemia occurred in 50%, but apnea did not occur in any of the patients studied. However, when the same doses of these drugs were administered together, 92% of participants exhibited hypoxemia and 50% became apneic.²

When a combination of an opioid and benzodiazepine are given over frequent intervals, the clinician crosses over from treating pain to performing procedural sedation and analgesia—whether he intended to or not. As such, the patient in this case required proper monitoring, including cardiac monitoring and pulse oximetry; he also should have been placed on supplemental O₂. Ideally, the patient would have benefited from end-tidal carbon dioxide (ETCO₂), monitoring, if available. This is a noninvasive measurement of the partial pressure of CO₂ in exhaled breath. Hypoventilation from respiratory depression results in an increase in ETCO₂, and hyperventilation results in a decreased ETCO₂. While pulse oximetry is excellent at monitoring O₂ saturation, it is ineffective in the early detection of respiratory depression, hypoventilation, and apnea. The hypercarbia precedes the hypoxemia—by as much as 60 seconds (range 5-240 seconds), according to a study by Deitch et al.³

Finally, rather than relying solely on the reports from the nurse, the EP should have personally reassessed the patient at some point. Nursing updates are extremely helpful, but when ordering repeated doses of IV opioids and benzodiazepines, the EP should personally reassess the patient.
 

Hot Red Knee

 64-year-old man presented to the ED with a chief complaint of right knee pain, which he stated began approximately 2 days earlier. He denied any injury or trauma or a recent history of fever, chills, or other joint complaints. He described the pain as constant, worse with weight bearing, and becoming progressively more painful. The patient had a history of gout; however, previous attacks had only affected his great toes and elbows. His medical history was also significant for hypertension, for which he was taking lisinopril and hydrochlorothiazide. He admitted to moderate alcohol consumption but denied tobacco use.

On physical examination, the patient appeared uncomfortable due to the knee pain. All of his vital signs were normal. A focused examination of the affected knee revealed a small effusion, diffuse tenderness to palpation, mild erythema, and slight increased warmth. The patient exhibited pain with flexion and extension of the right knee. The right ankle examination and right dorsalis pedis pulse and posterior tibial pulse were all normal. No laboratory or imaging studies were obtained.

Based on the patient’s history and physical examination, the EP believed the patient’s symptoms were due to an episode of gout. He prescribed oral colchicine, allopurinol, and acetaminophen/hydrocodone; he also advised the patient to apply warm compresses to the affected area and limit his activity. He discharged the patient home with instructions to follow up with his primary care physician.

Two days after discharge, the patient returned to the same ED via EMS. On this presentation, he was febrile, with a temperature of 102.6^oF; a HR of 120 beats/minute; and a BP of 92/50 mm Hg. He also had altered mental status. The patient’s right knee appeared more swollen, and he would not flex it due to the severe pain. The EP was concerned for sepsis, and ordered blood cultures, a complete blood count, basic metabolic profile, and lactic acid evaluation. The patient was administered 2 L normal saline IV and broad-spectrum antibiotics. Despite the addition of vasopressors, he continued to deteriorate; he ultimately went into cardiac arrest and died.

The patient’s family sued the EP from the initial ED visit for failure to diagnose the right knee pain and swelling as septic arthritis (SA). The plaintiff’s attorney argued that this failure to diagnosis directly caused the patient’s sepsis and death. The EP argued that the patient’s history and physical examination were consistent with an acute gout attack, that there was no evidence of infection in the right knee, and that this was not the cause of the patient’s death. At trial, the jury returned a verdict in favor of the defense.

Discussion

Gout is caused by the precipitation of uric acid crystals into a joint. Attacks are usually monoarticular as opposed to polyarticular. The presence of hyperuricemia is variable; some patients have high serum uric acid levels and never experience gout, while other patients have normal serum uric acid levels and experience gout attacks. The condition is more common in men than in women. There are multiple risk factors for the development of gout, including obesity, hypertension, chronic kidney disease, regular excessive consumption of alcohol, taking diuretics, and consuming foods high in fructose corn syrup.¹ The joints most often affected are the great toe and knee. Patients with gout typically complain of pain, swelling, redness, and increased warmth in the affected area.

Unfortunately, the clinical presentation of an acute gout attack and SA are indistinguishable.² Risk factors for SA include IV drug abuse, diabetes mellitus, having a prosthetic joint, immunosuppression, and human immunodeficiency virus infection. The only reliable way to distinguish between gout and SA requires arthrocentesis with microscopic examination of the synovial fluid for bacteria, crystals, white blood cell (WBC) count, and culture.²

It is critical not to miss SA because it is associated with significant morbidity and a mortality rate of 11%.² To further complicate the diagnosis, some patients can experience SA in the setting of an acute gout attack. In a study of all joint aspirations with crystals (both uric acid and calcium pyrophosphate), there was a 5.2% incidence of concomitant infection.² Similarly, in patients with confirmed SA, crystals were present 21% of the time.²

A gram stain of the synovial fluid is highly specific, but only positive in 59% of cases of SA. Therefore, a negative gram stain does not exclude the diagnosis. Similarly, the presence of crystals does not exclude a coexisting joint infection. If there is high clinical suspicion for SA or an elevated synovial WBC, the patient should be presumed to have SA and treated as such until cultures prove otherwise.

It is unclear if this patient had SA. However, an EP is taking a risk in diagnosing an acute gout attack based solely on a patient’s history and physical examination. The EP should always be mindful that gout and SA can present with the identical signs and symptoms, and can present concomitantly.

Too Much Medication, Too Little Monitoring

A 58-year-old man presented to the ED via emergency medical services (EMS) for evaluation of severe low-back pain. The patient said the pain started abruptly, approximately 1 hour earlier when he was picking up a 50-lb television set. He stated that the pain was so severe that he was unable to move and was forced to lie down on the floor. Although the patient noted that he had a history of a “bad back,” he said he never required surgery and never experienced an episode this severe. The patient denied any radiation of pain or lower extremity numbness or weakness. He denied any chest pain or abdominal pain. His medical history was significant for obstructive sleep apnea and hypertension for which he was taking hydrochlorothiazide. Regarding his social history, he denied any tobacco or alcohol use.

Upon presentation, the patient was found to be in extreme discomfort, rating his pain as an “11” on a scale of 0 to 10. His vital signs were heart rate (HR), 110 beats/minute; blood pressure (BP), 154/91 mm Hg; respiratory rate, 20 breaths/minute; and temperature, 98.6°F. Oxygen (O₂) saturation was 98% on room air.

When the emergency physician (EP) entered the examination room, the patient was in bed, resting on his side and moaning from the pain. The head, eyes, ears, nose, and throat, cardiac, and lung examinations were all normal. The patient’s abdomen was soft and nontender and without guarding, rebound, or palpable mass. When the EP examined the patient’s back, there was no midline tenderness over the thoracic and lumbar spine. The patient did, however, exhibit bilateral paraspinal lumbar muscle tenderness to palpation and muscle spasm. After much prompting, he demonstrated 5/5 motor strength in his lower extremities bilaterally. The dorsalis pedis and posterior tibial pulses were 2+ and symmetrical.

To treat the patient’s severe pain, the EP had a saline lock placed and ordered intravenous (IV) hydromorphone 1 mg, ondansetron 4 mg, and diazepam 5 mg. No laboratory or imaging studies were ordered. Ninety minutes after receiving the analgesics, the patient continued to complain of severe pain without any improvement, and the EP ordered another two rounds of IV hydromorphone 1 mg and diazepam 5 mg. The EP did not return to check up on the patient, but rather relied solely on updates from the patient’s nurse.

Despite the additional doses of hydromorphone and diazepam, the patient continued to complain of severe pain, and the EP ordered IV hydromorphone 2 mg and diazepam 10 mg. Shortly after the patient received this third round of analgesics, his wife arrived at the ED asking to see her husband. When she entered his room, the patient was unresponsive. A code was called and the patient was found to be in asystole. Despite aggressive resuscitative efforts that included intubation, cardiopulmonary resuscitation, and advanced cardiac life support medications, the patient did not recover.

The patient’s wife sued the EP, the ED nurse, and the hospital for failure to appropriately monitor her husband while he received multiple doses of analgesic and sedative agents. The plaintiff argued that the patient’s death was caused by a cardiac arrest occurring secondary to a respiratory arrest, and that the respiratory arrest was secondary to the medications he was given in the ED. The defendants denied the allegations. A $2 million settlement was reached prior to trial.

Discussion

This was clearly a preventable death. Emergency physicians treat pain daily and should be knowledgeable about and experienced in managing acute pain. When evaluating and treating a patient’s pain, the EP must select the appropriate medication. Though we often talk about a tiered approach to pain in the ED, most of us would agree that opioids, usually via IV, are the first choice for managing severe pain.

In addition to prescribing the appropriate analgesics, the EP must identify which patients are at risk of opioid complications. This patient was at risk for opioid-induced respiratory depression based on his age (ie, >55 years old) and history of obstructive sleep apnea. These two risk factors, along with pre-existing chronic obstructive pulmonary disease, anatomic oral or airway abnormalities, and comorbidities (eg, renal or hepatic impairment), place patients at high risk for opioid-associated complications.¹ Patients with any of these conditions must be closely monitored and, based on their response to the prescribed analgesia, the EP may need to decrease the analgesic dosage and increase dosage intervals. In addition to close monitoring, reversal agents such as naloxone should be readily available in case of respiratory depression.

The problem in this case was not the selection of hydromorphone as the initial analgesic agent. Hydromorphone is frequently used safely in the ED to treat severe pain associated with conditions such as sickle cell vaso-occlusive pain crisis, renal colic, and long-bone fracture. Issues arise when hydromorphone is combined with a benzodiazepine (in this case, diazepam), which by itself causes sedation and anxiolysis. Central nervous system (CNS) depression may be additive and occur when benzodiazepines are used concomitantly with drugs that also cause CNS depression (eg, opioids).¹ This combination can lead to excessive sedation, resulting in partial airway obstruction and hypoxia.¹ For example, in an investigation by Bailey et al,² in human volunteers, neither hypoxemia nor apnea was evident after administration of .05 mg/kg of IV midazolam. In patients who received 2 mcg/kg of IV fentanyl alone, hypoxemia occurred in 50%, but apnea did not occur in any of the patients studied. However, when the same doses of these drugs were administered together, 92% of participants exhibited hypoxemia and 50% became apneic.²

When a combination of an opioid and benzodiazepine are given over frequent intervals, the clinician crosses over from treating pain to performing procedural sedation and analgesia—whether he intended to or not. As such, the patient in this case required proper monitoring, including cardiac monitoring and pulse oximetry; he also should have been placed on supplemental O₂. Ideally, the patient would have benefited from end-tidal carbon dioxide (ETCO₂), monitoring, if available. This is a noninvasive measurement of the partial pressure of CO₂ in exhaled breath. Hypoventilation from respiratory depression results in an increase in ETCO₂, and hyperventilation results in a decreased ETCO₂. While pulse oximetry is excellent at monitoring O₂ saturation, it is ineffective in the early detection of respiratory depression, hypoventilation, and apnea. The hypercarbia precedes the hypoxemia—by as much as 60 seconds (range 5-240 seconds), according to a study by Deitch et al.³

Finally, rather than relying solely on the reports from the nurse, the EP should have personally reassessed the patient at some point. Nursing updates are extremely helpful, but when ordering repeated doses of IV opioids and benzodiazepines, the EP should personally reassess the patient.
 

Hot Red Knee

 64-year-old man presented to the ED with a chief complaint of right knee pain, which he stated began approximately 2 days earlier. He denied any injury or trauma or a recent history of fever, chills, or other joint complaints. He described the pain as constant, worse with weight bearing, and becoming progressively more painful. The patient had a history of gout; however, previous attacks had only affected his great toes and elbows. His medical history was also significant for hypertension, for which he was taking lisinopril and hydrochlorothiazide. He admitted to moderate alcohol consumption but denied tobacco use.

On physical examination, the patient appeared uncomfortable due to the knee pain. All of his vital signs were normal. A focused examination of the affected knee revealed a small effusion, diffuse tenderness to palpation, mild erythema, and slight increased warmth. The patient exhibited pain with flexion and extension of the right knee. The right ankle examination and right dorsalis pedis pulse and posterior tibial pulse were all normal. No laboratory or imaging studies were obtained.

Based on the patient’s history and physical examination, the EP believed the patient’s symptoms were due to an episode of gout. He prescribed oral colchicine, allopurinol, and acetaminophen/hydrocodone; he also advised the patient to apply warm compresses to the affected area and limit his activity. He discharged the patient home with instructions to follow up with his primary care physician.

Two days after discharge, the patient returned to the same ED via EMS. On this presentation, he was febrile, with a temperature of 102.6^oF; a HR of 120 beats/minute; and a BP of 92/50 mm Hg. He also had altered mental status. The patient’s right knee appeared more swollen, and he would not flex it due to the severe pain. The EP was concerned for sepsis, and ordered blood cultures, a complete blood count, basic metabolic profile, and lactic acid evaluation. The patient was administered 2 L normal saline IV and broad-spectrum antibiotics. Despite the addition of vasopressors, he continued to deteriorate; he ultimately went into cardiac arrest and died.

The patient’s family sued the EP from the initial ED visit for failure to diagnose the right knee pain and swelling as septic arthritis (SA). The plaintiff’s attorney argued that this failure to diagnosis directly caused the patient’s sepsis and death. The EP argued that the patient’s history and physical examination were consistent with an acute gout attack, that there was no evidence of infection in the right knee, and that this was not the cause of the patient’s death. At trial, the jury returned a verdict in favor of the defense.

Discussion

Gout is caused by the precipitation of uric acid crystals into a joint. Attacks are usually monoarticular as opposed to polyarticular. The presence of hyperuricemia is variable; some patients have high serum uric acid levels and never experience gout, while other patients have normal serum uric acid levels and experience gout attacks. The condition is more common in men than in women. There are multiple risk factors for the development of gout, including obesity, hypertension, chronic kidney disease, regular excessive consumption of alcohol, taking diuretics, and consuming foods high in fructose corn syrup.¹ The joints most often affected are the great toe and knee. Patients with gout typically complain of pain, swelling, redness, and increased warmth in the affected area.

Unfortunately, the clinical presentation of an acute gout attack and SA are indistinguishable.² Risk factors for SA include IV drug abuse, diabetes mellitus, having a prosthetic joint, immunosuppression, and human immunodeficiency virus infection. The only reliable way to distinguish between gout and SA requires arthrocentesis with microscopic examination of the synovial fluid for bacteria, crystals, white blood cell (WBC) count, and culture.²

It is critical not to miss SA because it is associated with significant morbidity and a mortality rate of 11%.² To further complicate the diagnosis, some patients can experience SA in the setting of an acute gout attack. In a study of all joint aspirations with crystals (both uric acid and calcium pyrophosphate), there was a 5.2% incidence of concomitant infection.² Similarly, in patients with confirmed SA, crystals were present 21% of the time.²

A gram stain of the synovial fluid is highly specific, but only positive in 59% of cases of SA. Therefore, a negative gram stain does not exclude the diagnosis. Similarly, the presence of crystals does not exclude a coexisting joint infection. If there is high clinical suspicion for SA or an elevated synovial WBC, the patient should be presumed to have SA and treated as such until cultures prove otherwise.

It is unclear if this patient had SA. However, an EP is taking a risk in diagnosing an acute gout attack based solely on a patient’s history and physical examination. The EP should always be mindful that gout and SA can present with the identical signs and symptoms, and can present concomitantly.

Patients with a health care-acquired infection had a larger proportion of readmissions, greater associated costs, and higher mortality rates compared to patients with no HAI, according to a study published in the American Journal of Infection Control.

Investigators at Linköping (Sweden) University examined the effects of HAIs by calculating the difference in hospital length of stay (LOS) and actual direct health care costs for patients with an HAI compared with patients without HAI. They used data from the Swedish National Point Prevalence Surveys of HAI 2010-2012, merged with cost-per-patient data from the Health Care Register of the Swedish county of Östergötland. Extended LOS and costs related to an HAI were adjusted for sex, age, intensive care unit use, and surgery.

The average prevalence of HAI for all 7,981 patients in the study was 10.8%, although for the 7,062 patients in the main analyses the prevalence of HAI in the Point Prevalence Survey was 9.9%. Those patients with HAI (732 patients) had a larger proportion of readmissions compared with patients with no HAI (29.0% vs 16.5%), a significant difference, said Mikael Rahmqvist, Ph.D., of the department of medical and health sciences at Linköping University, and lead author of the study.

Of the total hospital bed days occupied by patients in the study population, 9.3% was considered to be excess days, attributed to the group of patients with an HAI. This excess LOS comprised 11.4% of total health care costs (95% confidence interval, 10.2-12.7). The 1-year overall mortality rate for patients with HAI in comparison to all other patients was 1.75 (95% CI, 1.45-2.11). The coauthors said all of the differences measured were statistically significant (P less than .001).

“Our results imply that a reduction of HAI prevalence to a significant degree could reduce health care costs, lessen patient suffering, and also increase patients’ long-term survival,” said Dr. Rahmqvist and his coauthors.

They reported having no conflicts.

Read the full study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.035).

[email protected]

On Twitter @richpizzi

Patients with a health care-acquired infection had a larger proportion of readmissions, greater associated costs, and higher mortality rates compared to patients with no HAI, according to a study published in the American Journal of Infection Control.

Investigators at Linköping (Sweden) University examined the effects of HAIs by calculating the difference in hospital length of stay (LOS) and actual direct health care costs for patients with an HAI compared with patients without HAI. They used data from the Swedish National Point Prevalence Surveys of HAI 2010-2012, merged with cost-per-patient data from the Health Care Register of the Swedish county of Östergötland. Extended LOS and costs related to an HAI were adjusted for sex, age, intensive care unit use, and surgery.

The average prevalence of HAI for all 7,981 patients in the study was 10.8%, although for the 7,062 patients in the main analyses the prevalence of HAI in the Point Prevalence Survey was 9.9%. Those patients with HAI (732 patients) had a larger proportion of readmissions compared with patients with no HAI (29.0% vs 16.5%), a significant difference, said Mikael Rahmqvist, Ph.D., of the department of medical and health sciences at Linköping University, and lead author of the study.

Of the total hospital bed days occupied by patients in the study population, 9.3% was considered to be excess days, attributed to the group of patients with an HAI. This excess LOS comprised 11.4% of total health care costs (95% confidence interval, 10.2-12.7). The 1-year overall mortality rate for patients with HAI in comparison to all other patients was 1.75 (95% CI, 1.45-2.11). The coauthors said all of the differences measured were statistically significant (P less than .001).

“Our results imply that a reduction of HAI prevalence to a significant degree could reduce health care costs, lessen patient suffering, and also increase patients’ long-term survival,” said Dr. Rahmqvist and his coauthors.

They reported having no conflicts.

Read the full study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.035).

[email protected]

On Twitter @richpizzi

Patients with a health care-acquired infection had a larger proportion of readmissions, greater associated costs, and higher mortality rates compared to patients with no HAI, according to a study published in the American Journal of Infection Control.

Investigators at Linköping (Sweden) University examined the effects of HAIs by calculating the difference in hospital length of stay (LOS) and actual direct health care costs for patients with an HAI compared with patients without HAI. They used data from the Swedish National Point Prevalence Surveys of HAI 2010-2012, merged with cost-per-patient data from the Health Care Register of the Swedish county of Östergötland. Extended LOS and costs related to an HAI were adjusted for sex, age, intensive care unit use, and surgery.

The average prevalence of HAI for all 7,981 patients in the study was 10.8%, although for the 7,062 patients in the main analyses the prevalence of HAI in the Point Prevalence Survey was 9.9%. Those patients with HAI (732 patients) had a larger proportion of readmissions compared with patients with no HAI (29.0% vs 16.5%), a significant difference, said Mikael Rahmqvist, Ph.D., of the department of medical and health sciences at Linköping University, and lead author of the study.

Of the total hospital bed days occupied by patients in the study population, 9.3% was considered to be excess days, attributed to the group of patients with an HAI. This excess LOS comprised 11.4% of total health care costs (95% confidence interval, 10.2-12.7). The 1-year overall mortality rate for patients with HAI in comparison to all other patients was 1.75 (95% CI, 1.45-2.11). The coauthors said all of the differences measured were statistically significant (P less than .001).

“Our results imply that a reduction of HAI prevalence to a significant degree could reduce health care costs, lessen patient suffering, and also increase patients’ long-term survival,” said Dr. Rahmqvist and his coauthors.

They reported having no conflicts.

Read the full study in the American Journal of Infection Control (doi:10.1016/j.ajic.2016.01.035).

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.

Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.

Courtesy NIH

A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.

Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.

A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.

Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.

Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log₁₀ IU/mL to interrupt mother-to-infant transmission.

A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.

A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.

New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.

Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.

Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.

Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.

As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.

A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.

Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.

Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.

A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.

A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.

A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.

Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.

Courtesy NIH

A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.

Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.

A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.

Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.

Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log₁₀ IU/mL to interrupt mother-to-infant transmission.

A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.

A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.

New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.

Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.

Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.

Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.

As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.

A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.

Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.

Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.

A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.

A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.

A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.

[email protected]

On Twitter @richpizzi

If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month covering a variety of the major hepatitis viruses.

Elderly patients with chronic hepatitis C disease are more likely to develop hepatocellular carcinoma (HCC) than younger patients, but they have traditionally received less antiviral treatment than younger patients, according to a study in the Journal of Viral Hepatitis. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC, and overall mortality, irrespective of age, investigators said.

Courtesy NIH

A report in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report from the Texas Department of State Health Services detailed how the agency dealt with a health care–associated hepatitis A outbreak in August 2015.

Researchers at McGill University in Montreal have developed a portable, paper-based electrochemical platform with multiplexing and telemedicine capabilities that may enable low-cost, point-of-care diagnosis of hepatitis C virus (HCV) and HIV co-infections within serum samples.

A study of patients at a gastroenterology clinic in Cameroon found that almost 40% of patients who were anti-hepatitis C virus antibody-positive were also asymptomatic, and some already presented with complications, including cirrhosis and hepatocellular carcinoma. The authors highlighted an urgent need to put in place programs to increase awareness and diagnosis of HCV infection in the country.

Chronic hepatitis C virus infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis, according to a review of epidemiologic studies.

Quantitative maternal surface antigen (HBsAg) predicts hepatitis B virus infection in infants as well as maternal viral load does, according to a study in Hepatology. The authors conclude that antiviral therapy may be considered in pregnant women with an HBsAg level above 4-4.5 log₁₀ IU/mL to interrupt mother-to-infant transmission.

A comprehensive literature review of cited WHO estimates for hepatitis B virus (HBV), HCV, and HIV co-infection between 2010 and 2014 showed that a wide range of co-infection estimates have been quoted using different WHO estimates. The authors detail the most recent, appropriate WHO estimates that should be used going forward.

A Chinese cohort study found that isolated anti-HBc–positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and geometric mean titer (GMT) level for anti-HBs were lower than in a control group. Better responses were observed in young adults, the study authors said, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.

New research indicates that evidence of long-lasting cellular immunity, regardless of anti-hepatitis B surface antigen level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.

Increased knowledge of hepatitis B cognition is an effective way for improving hepatitis B vaccination behavior and hepatitis B vaccination willingness of migrant workers, report the authors of a study in Human Vaccines & Immunotherapeutics. The researchers also found that health intervention policies should focus on older migrants (age at least 46 years) without medical insurance, with poorer self-reported health status, and poor health services accessibility.

Hepatitis B virus antibodies and galactomannan enzyme immunoassay (GM-EIA) positivity are common in patients receiving intravenous immunoglobulin and may confound diagnostic results, according to a study in Clinical Infectious Diseases.

Researchers in Niger have identified two recombinant hepatitis B virus forms and rare genotypic patterns that may affect hepatitis B surface antigen antigenicity and improve current knowledge of epidemiological, clinical, and virological patterns of hepatitis B in that country.

As viral hepatitis can be life threatening in patients with hematological malignancy, a new study suggests that all patients should be screened for hepatotropic viruses before hematological treatment, and that patients or hemopoietic stem cell donors with markers of past or current viral hepatitis should be assessed by an expert. The study also includes screening, vaccination, and treatment rules.

A study published in JAIDS suggests that lamivudine (3TC) monotherapy-based combination antiretroviral therapy is efficacious for hepatitis B virus treatment through 48 weeks in HIV/HBV coinfection, when baseline HBV DNA is less than 20,000 IU/mL.

Chinese researchers observed a significant elevation in CD4+Foxp3+ regulatory T-cells (Treg) in the peripheral blood of chronic hepatitis C patients, compared with healthy donors, in a study published in the International Journal of Infectious Diseases. The results demonstrate a decreasing trend in activated Treg cells after treatment with interferon alpha and ribavirin in vitro, the investigators also said.

Research published in Hepatology suggests hepatitis B virus e antigen (HBeAg) and its precursors promote HDM2-mediated degradation and impair the transcriptional activity of tumor suppressor p53 via interacting with the NUMB gene, consequently contributing to hepatocellular carcinoma development.

A systematic review of recent hepatitis B vaccine research highlighted the importance of introducing HBV vaccination not only for an infant universal vaccination program, but also for other settings in which patients are affected by communicable and noncommunicable diseases.

A “real-world” cohort study of 4,365 genotype 1 treatment-naïve hepatitis C virus–infected veterans treated with ledipasvir/sofosbuvir with or without ribavirin found that sustained virologic response (SVR) rates in the cohort nearly matched the SVR rates reported in clinical trials and were consistently high across all subgroups. Investigators found that noncirrhotics with HCV RNA less than 6,000,000 IU/mL were less likely to achieve SVR with 8 weeks, compared with 12 weeks of therapy, although the numeric difference in SVR rates was small.

A study in the Journal of Viral Hepatitis demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the hepatitis B DNA vaccine pSVK-HBVA, and that the DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.

[email protected]

On Twitter @richpizzi

The chaos of a busy ED can test the cognitive reserve of even the most focused practitioner. To streamline the challenge of serial diagnosis and treatment, clinicians employ heuristics while honing the skills of pattern recognition. However, by definition, heuristics employs shortcuts, leaving out information for the sake of efficiency—sometimes at the expense of accuracy. Whether a patient presents with chest pain, abdominal pain, headache, or (the dreaded) dizziness, emergency physicians (EPs) employ algorithms based on a combination of education and prior experience.

Most of the time, these models lead the EP along the correct path, but not always. For example, when a clinician evaluating a patient presenting with psychotic behavior assumes the patient has schizophrenia, he or she will be correct eight or nine times out of 10. However, in some cases, a patient’s bizarre behavior may not be due to a true psychiatric disorder but, for example, from ingestion of an illicit substance.

In addition, in such patients, psychiatric symptoms may be masking a serious acute, organic condition—one requiring prompt intervention and therapy to avoid morbidity or death. To help prevent diagnostic errors, this 2-part series reviews several of the most common medical mimics of psychiatric conditions. Part 1 of this series reviews the psychiatric presentations associated with medical conditions of an infectious, pharmacological withdrawal, metabolic, autoimmune, traumatic, or central nervous system etiology (Table 1). This article also discusses clinical signs and symptoms that suggest an increased likelihood that a patient’s psychiatric symptoms are from an underlying medical condition (Table 2).

Case Scenarios

Case 1

A 58-year-old woman with a history of smoking 40 packs of cigarettes per year presented to the ED 1 hour after onset of intermittent chest pain. Upon arrival at the ED, the patient stated that she had trouble catching her breath on and off throughout the day. The patient’s vital signs, electrocardiogram (ECG), and chest X-ray were all normal. The physical examination was unremarkable except for mild diaphoresis. The patient denied experiencing palpitations, recent travel, or previous episodes; she further stated that she was currently not on any medications. There was no previous history of visits to this hospital. The patient’s husband, who accompanied her to the ED, noted that his wife’s behavior had been atypical for approximately 1 week.

After receiving aspirin, the patient appeared symptom-free. Pending the results of another chest radiograph and laboratory evaluation, the EP anticipated moving her to the chest-pain observation unit.

Case 2

A 36-year-old woman presented with altered mental status to the ED via emergency medical services (EMS). Her vital signs, including temperature, were normal. Despite intermittently appearing to be asleep, the patient was alternatingly cooperative and combative. She repetitively whispered, “Who am I?” and randomly shouted at staff members as they walked by her room.

Her neurological examination was nonfocal. The hospital’s electronic medical record (EMR) for this patient showed nearly monthly ED visits for behavioral symptoms. Precipitating events noted in the EMR included job loss and separation from her husband. While waiting for the results of the basic laboratory work-up and toxicology screening to medically clear the patient for psychiatric evaluation, the EP contemplated a computed tomography (CT) study. Realizing the patient would not be able to remain still for the scan, the EP ordered 10 mg of intramuscular ziprasidone for sedation. When the patient’s husband arrived, the EP placed the CT scan on hold until she could obtain additional history from him.

Infections

Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is a serious but treatable disease—one that requires early detection and treatment to avoid severe morbidity. While the classic symptoms are fever and altered mental status, recent literature has noted that afebrile patients with HSE may present with behavioral changes, cognitive decline, aggression, and disinhibition. Therefore, diagnosis of a functional psychiatric complaint, if made initially, could delay appropriate treatment with acyclovir.¹

Human Immunodeficiency Virus

Progression of human immunodeficiency virus (HIV) is a well-known cause of various neurocognitive disorders, including early-onset dementia. Since the availability of highly active antiretroviral therapy, the incidence of HIV dementia has decreased, but HIV remains the most common preventable cause of dementia in persons younger than age 50 years. Recent literature has described HIV dementia presenting as an early-onset, rapidly progressing dementia in a young person. Thus, the EP should consider early HIV testing in any young patient who presents with dementia, especially one with a history of fever of unknown origin.²

Progressive Multifocal Encephalopathy

Caused by reactivation of the John Cunningham virus, progressive multifocal encephalopathy has been classically described as a potentially lethal complication of a severely immunocompromised state, often presenting with clumsiness, weakness, visual changes, speech difficulty, and behavioral changes. Though typically described as occurring in the context of acquired immunodeficiency disease syndrome, hematological malignancy, or organ transplant, the condition can occur in the setting of minimal or occult immunosuppression—especially in patients with a history of cirrhosis. If the condition is detected early, immunotherapy can result in significant clinical improvement.³

Syphilis

Late stages of syphilis can present with a wide variety of psychiatric symptoms, including personality disorder, psychosis, delirium, and dementia. As with HIV, there has been a resurgence of syphilis cases, and screening is now often a routine part of a neuropsychiatric work-up. The EP should consider syphilis in the differential for any new-onset psychiatric complaint.^4,5

Typhoid Fever

Although this severe febrile illness is uncommon in the United States, it is endemic to many tropical countries within Africa, Southeast Asia, and Central and South America. Typhoid is characterized by a stepwise fever that can progress to abdominal distension, toxemia, and potentially bowel perforation. It is also known to present with psychiatric symptoms such as acute confusion, psychosis, generalized anxiety disorder, and, though rare, depressive disorder. Physicians traveling to rural endemic areas should be aware of these neuropsychiatric presentations to avoid misdiagnosis and delay of treatment.⁶ Other infectious endemic diseases with reports of neuropsychiatric components are neurocystercercosis, Lyme disease, and African trypanosomiasis.

Pharmacological Withdrawal Syndromes

Alcohol

Alcohol withdrawal is a common presentation in the ED, and up to 24% of US adults brought to the ED by EMS suffer from alcoholism. Typically characterized by tachycardia, hypertension, and tremors, alcohol withdrawal syndrome can also feature psychiatric components such as agitation, hallucinations, persecutory delusions, and even self-mutilation.⁷ Evidence-based protocols indicate loading doses of benzodiazepines as a mainstay of treatment, with supplemental barbiturates or propofol in cases of treatment failure.⁸

Benzodiazepines

Withdrawal from therapeutic doses of benzodiazepines can potentially cause psychiatric symptoms, including sleep disturbances, irritability, anxiety, panic attacks, tremor, and perceptual changes. Withdrawal from higher doses of benzodiazepines can lead to more serious presentations, such as seizures and acute psychosis.⁹ Withdrawal symptoms can develop from discontinuation of the drug and with non-tapered switching between benzodiazepines.¹⁰

Opiates

Opiate withdrawal is an unpleasant experience characterized by generalized pain, nausea and vomiting, sweating, and tachycardia. Neuropsychiatric complaints such as anxiety, agitation, and irritability can also be present. More severe agitation has been described in naltrexone-accelerated detoxification^.11

Cannabis

Recent literature on cannabis use indicates a high prevalence and clinical significance of associated withdrawal symptoms in frequent users. There appear to be two subsets of cannabis withdrawal—one characterized by weakness and hypersomnia, and the other by anxiety, depression, restlessness, and insomnia.¹²

Estrogen

Withdrawal from endogenous estrogen has been hypothesized as a possible cause of puerperal psychosis.¹³ Estrogen withdrawal outside of this setting, however, can and does occur, and recent literature has shown episodes of reversible psychosis associated with the discontinuation of both oral contraceptive regimens and hormonal therapy for menopausal symptoms.

Acute Metabolic Conditions

Hypoglycemia

Hypoglycemia, most often encountered as a side effect of insulin or oral hypoglycemic therapies, is a potentially lethal cause of confusion, anxiety, nervousness, and seizures. Nocturnal hypoglycemia can manifest as nightmares, crying out, and confusion upon awakening. A fingerstick blood-glucose test is an absolutely vital part of the initial work-up of any patient with an altered mental status or overt psychiatric complaint.¹⁴

Central Pontine Myelinolysis

A potentially devastating neurological condition associated with malnourishment and alcohol dependence, central pontine myelinolysis (CPM) is classically exacerbated by rapid overcorrection of hyponatremia. While the disease can manifest primarily with quadriplegia or pseudobulbar palsy and eventual progress to the dreaded “locked-in” syndrome, early presentations can include psychiatric symptoms such as behavioral changes, psychosis, and cognitive disturbances. Patients with early signs and symptoms of CPM have been misdiagnosed as having schizophrenia with catatonia, leading to delayed treatment and poor outcomes. The EP should remain vigilant when evaluating for this condition and consider a magnetic resonance imaging study in patients with psychiatric symptoms in the setting of fluctuating hyponatremia.¹⁵

Autoimmune Disorders

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders, and has a higher incidence in young women. The disease affects multiple organ systems. Though the classic initial presentation of SLE is fever, joint pain, and rash, the associated neuropsychiatric syndromes of this disease are diverse and surprisingly common, and can be the initial manifestation of the disease. Common psychiatric manifestations of SLE include cognitive dysfunction, anxiety, mood disorders such as depression, acute confusion, psychosis, paranoia, and auditory or visual hallucinations.¹⁶

Anti-N-methyl-D-Aspartate Receptor Encephalitis

Initially described as a paraneoplastic effect of ovarian teratomas, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is actually an autoimmune disorder that can occur even in the absence of a primary tumor. As with SLE, the condition primarily occurs in young women. Antibodies in the cerebrospinal fluid cause prominent psychiatric symptoms such as acute psychosis, delusional thinking, hallucinations, agitation, and confusion. Although the disease can progress to seizures, movement disorders, autonomic dysregulation, and ultimately death, early recognition and treatment can lead to positive outcomes in up to 80% of cases.¹⁷ While the prevalence of anti-NMDAR antibodies in new-onset psychosis remains unclear, recent literature has suggested widespread screening for the disease in all first presentations of psychotic episodes.^18,19

Multiple Sclerosis

Multiple sclerosis (MS) is another autoimmune disorder that has a higher prevalence in young women. The disease is characterized by central nervous system involvement that occurs over a period of months to years, with symptoms corresponding to different anatomic locations. Though the classic presenting symptom of MS is optic neuritis, neuropsychiatric syndromes are a common co-occurrence and can be the initial presenting symptom. The most commonly associated psychiatric complaints are anxiety, depression, and bipolar disorder, though case reports of SLE have described acute psychosis, psychotic depression, and adult-onset tic disorder.²⁰

Trauma

Subarachnoid Hemorrhage

Long-term psychiatric sequelae from subarachnoid hemorrhage, either traumatic or aneurysmal, manifest most commonly as personality changes, intellectual impairment, depression, and anxiety. This condition is also known to cause a host of more bizarre psychiatric presentations, such as new-onset kleptomania, akinetic mutism, confabulatory amnesia, acute psychosis, and Capgras syndrome (the delusion that familiar individuals have been replaced by imposters). These symptoms can occur at initial presentation, and may show variable improvement with shunt surgery.²¹

Subdural Hematoma

Acute or chronic subdural hematoma can result from major head trauma, or even quite minor head trauma in an elderly or coagulopathic patient. Some common psychiatric manifestations of subdural hematoma include cognitive impairment, withdrawn behavior, blunted affect otherwise mimicking schizophrenic psychosis, and catatonia. The EP should consider early imaging studies in patients with new-onset psychotic symptoms—especially when they are refractory to typical antipsychotics.²²

Central Nervous Symptom Diseases

Huntington Disease

Huntington disease (HD) is an autosomal dominant inherited, progressive neurodegenerative disorder characterized by mental decline, mood disorder, and muscle coordination problems that eventually become the classic involuntary writhing termed chorea. Due to its progressive nature, precise onset of the disease is difficult to describe; however, HD can manifest initially as schizophrenia-like psychotic episodes with only minimal apparent motor difficulty. Family history, including movement disorders and suicide, is important to obtain when available.²³

Parkinson Disease

A progressive and disabling neurodegenerative disorder, Parkinson disease (PD) is classically characterized by fine resting tremor, cogwheeling rigidity, akinesia and mask-like facies, and postural instability. Comorbidity of psychiatric disorders is high, both as a result of the underlying disease process and as a side effect of dopaminergic treatment regimes. Common presentations of psychiatric disorders in PD include schizophrenia-like psychosis with visual hallucinations and mood disorders with prominent apathy and executive dysfunction. Recognition of the comorbidity is important because psychiatric disorders in PD respond differently to treatment than classic psychiatric disorders.²⁴

Temporal Lobe Epilepsy

Epilepsy is a complex group of related neurological disorders involving unregulated nerve cell firing with a large variability in clinical presentation. Characteristically there is recurrent seizure activity. Temporal lobe epilepsy (TLE) is a subset of epilepsy known to present as a number of behavioral and neuropsychiatric complaints. Most presentations of TLE involve auras of emotional phenomena such as depression, fear, or anxiety, which can occur alone or with subsequent progression to complex partial or secondary generalized seizures.²⁵ Many other bizarre presentations of TLE have been reported, including recurrent, potentially debilitating déjà vu, vivid recollection of past traumatic events mimicking posttraumatic stress disorder, paranoid delusions following olfactory triggers; and unprovoked attacks of depersonalization, derealization, anxiety, and dyspnea originally misdiagnosed as panic attack.

Stroke

The term “stroke chameleon” refers to presentations suggestive of other diseases that actually represent underlying strokes. Altered mental status is by far the largest block of these chameleons, with up to 30% of misdiagnosed strokes being misdiagnosed as altered mental status. The positive predictive value of altered mental status alone (ie, the chance that the diagnosis of altered mental status actually represents an undiagnosed acute stroke) is 7%.²⁶

Case Scenarios Continued

Case 1

[The 58-year-old woman with intermittent chest pain.]

The patient’s D-dimer and troponin I levels were normal. Before the EP had an opportunity to discuss the results and next steps with the patient, the nurse asked him to see the patient immediately. Upon entering her room, the EP noted that the patient appeared anxious. The patient said the shortness of breath had returned, and also that she felt as if she were “floating” off the gurney, outside of her body. A check of her vital signs revealed a heart rate of 106 beats/minute and blood pressure of 160/100 mm Hg. A repeat ECG was significant only for sinus tachycardia. In an effort to calm the patient, the EP reassured her that the ECG, chest X-ray, and screening laboratory studies were normal, and that there was no evidence of a heart attack. Relieved, the patient asked for an Ativan to calm her nerves. Upon further questioning, the patient sheepishly reported that she had been taking 3 to 6 mg lorazepam for about 10 years, as prescribed by her family physician (FP) for anxiety. She further admitted that she abruptly discontinued taking the drug about one week before this ED visit after she’d heard on a daytime TV show that the medication was addictive.

After receiving lorazepam, the patient showed marked improvement. The EP’s final impressions were atypical chest pain and acute panic attack precipitated by abrupt benzodiazepine withdrawal. After discussing the case with the patient’s FP, the EP discharged the patient home with instructions to complete the cardiac evaluation as an outpatient. The EP also recommended that the patient resume taking lorazepam and follow-up with her FP within one week to discuss a benzodiazepine taper and alternative therapy for anxiety.

Case 2

[The 36-year-old woman with altered mental status.]

When the EP entered the patient’s room, he witnessed the patient staring at her husband and striking him repetitively with her right arm. When the EP asked the patient to stop hitting, her husband told the EP that everything was alright and that the patient’s neurologist had previously told them this behavior was caused by a seizure. While in the next examination room, one of the EP’s colleagues had overheard some of the patient’s history and recognized the name of the patient’s neurologist as a specialist in partial complex seizures—one who had retired from the local medical school about 10 years ago.

After records from the local university hospital confirmed the patient’s diagnosis of partial complex seizures, she was given intravenous lorazepam 2 mg; she became alert, conversational, and stopped flailing her right arm. She was then admitted to the hospital for medical stabilization of her frequent seizures.

Editor’s Note: Part 2 of this article will appear in the June 2016 issue of Emergency Medicine and will cover psychiatric presentations related to dementia, cancer, cardiac disease, nutritional deficiencies, endocrine disorders, and toxins.

The chaos of a busy ED can test the cognitive reserve of even the most focused practitioner. To streamline the challenge of serial diagnosis and treatment, clinicians employ heuristics while honing the skills of pattern recognition. However, by definition, heuristics employs shortcuts, leaving out information for the sake of efficiency—sometimes at the expense of accuracy. Whether a patient presents with chest pain, abdominal pain, headache, or (the dreaded) dizziness, emergency physicians (EPs) employ algorithms based on a combination of education and prior experience.

Most of the time, these models lead the EP along the correct path, but not always. For example, when a clinician evaluating a patient presenting with psychotic behavior assumes the patient has schizophrenia, he or she will be correct eight or nine times out of 10. However, in some cases, a patient’s bizarre behavior may not be due to a true psychiatric disorder but, for example, from ingestion of an illicit substance.

In addition, in such patients, psychiatric symptoms may be masking a serious acute, organic condition—one requiring prompt intervention and therapy to avoid morbidity or death. To help prevent diagnostic errors, this 2-part series reviews several of the most common medical mimics of psychiatric conditions. Part 1 of this series reviews the psychiatric presentations associated with medical conditions of an infectious, pharmacological withdrawal, metabolic, autoimmune, traumatic, or central nervous system etiology (Table 1). This article also discusses clinical signs and symptoms that suggest an increased likelihood that a patient’s psychiatric symptoms are from an underlying medical condition (Table 2).

Case Scenarios

Case 1

A 58-year-old woman with a history of smoking 40 packs of cigarettes per year presented to the ED 1 hour after onset of intermittent chest pain. Upon arrival at the ED, the patient stated that she had trouble catching her breath on and off throughout the day. The patient’s vital signs, electrocardiogram (ECG), and chest X-ray were all normal. The physical examination was unremarkable except for mild diaphoresis. The patient denied experiencing palpitations, recent travel, or previous episodes; she further stated that she was currently not on any medications. There was no previous history of visits to this hospital. The patient’s husband, who accompanied her to the ED, noted that his wife’s behavior had been atypical for approximately 1 week.

After receiving aspirin, the patient appeared symptom-free. Pending the results of another chest radiograph and laboratory evaluation, the EP anticipated moving her to the chest-pain observation unit.

Case 2

A 36-year-old woman presented with altered mental status to the ED via emergency medical services (EMS). Her vital signs, including temperature, were normal. Despite intermittently appearing to be asleep, the patient was alternatingly cooperative and combative. She repetitively whispered, “Who am I?” and randomly shouted at staff members as they walked by her room.

Her neurological examination was nonfocal. The hospital’s electronic medical record (EMR) for this patient showed nearly monthly ED visits for behavioral symptoms. Precipitating events noted in the EMR included job loss and separation from her husband. While waiting for the results of the basic laboratory work-up and toxicology screening to medically clear the patient for psychiatric evaluation, the EP contemplated a computed tomography (CT) study. Realizing the patient would not be able to remain still for the scan, the EP ordered 10 mg of intramuscular ziprasidone for sedation. When the patient’s husband arrived, the EP placed the CT scan on hold until she could obtain additional history from him.

Infections

Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is a serious but treatable disease—one that requires early detection and treatment to avoid severe morbidity. While the classic symptoms are fever and altered mental status, recent literature has noted that afebrile patients with HSE may present with behavioral changes, cognitive decline, aggression, and disinhibition. Therefore, diagnosis of a functional psychiatric complaint, if made initially, could delay appropriate treatment with acyclovir.¹

Human Immunodeficiency Virus

Progression of human immunodeficiency virus (HIV) is a well-known cause of various neurocognitive disorders, including early-onset dementia. Since the availability of highly active antiretroviral therapy, the incidence of HIV dementia has decreased, but HIV remains the most common preventable cause of dementia in persons younger than age 50 years. Recent literature has described HIV dementia presenting as an early-onset, rapidly progressing dementia in a young person. Thus, the EP should consider early HIV testing in any young patient who presents with dementia, especially one with a history of fever of unknown origin.²

Progressive Multifocal Encephalopathy

Caused by reactivation of the John Cunningham virus, progressive multifocal encephalopathy has been classically described as a potentially lethal complication of a severely immunocompromised state, often presenting with clumsiness, weakness, visual changes, speech difficulty, and behavioral changes. Though typically described as occurring in the context of acquired immunodeficiency disease syndrome, hematological malignancy, or organ transplant, the condition can occur in the setting of minimal or occult immunosuppression—especially in patients with a history of cirrhosis. If the condition is detected early, immunotherapy can result in significant clinical improvement.³

Syphilis

Late stages of syphilis can present with a wide variety of psychiatric symptoms, including personality disorder, psychosis, delirium, and dementia. As with HIV, there has been a resurgence of syphilis cases, and screening is now often a routine part of a neuropsychiatric work-up. The EP should consider syphilis in the differential for any new-onset psychiatric complaint.^4,5

Typhoid Fever

Although this severe febrile illness is uncommon in the United States, it is endemic to many tropical countries within Africa, Southeast Asia, and Central and South America. Typhoid is characterized by a stepwise fever that can progress to abdominal distension, toxemia, and potentially bowel perforation. It is also known to present with psychiatric symptoms such as acute confusion, psychosis, generalized anxiety disorder, and, though rare, depressive disorder. Physicians traveling to rural endemic areas should be aware of these neuropsychiatric presentations to avoid misdiagnosis and delay of treatment.⁶ Other infectious endemic diseases with reports of neuropsychiatric components are neurocystercercosis, Lyme disease, and African trypanosomiasis.

Pharmacological Withdrawal Syndromes

Alcohol

Alcohol withdrawal is a common presentation in the ED, and up to 24% of US adults brought to the ED by EMS suffer from alcoholism. Typically characterized by tachycardia, hypertension, and tremors, alcohol withdrawal syndrome can also feature psychiatric components such as agitation, hallucinations, persecutory delusions, and even self-mutilation.⁷ Evidence-based protocols indicate loading doses of benzodiazepines as a mainstay of treatment, with supplemental barbiturates or propofol in cases of treatment failure.⁸

Benzodiazepines

Withdrawal from therapeutic doses of benzodiazepines can potentially cause psychiatric symptoms, including sleep disturbances, irritability, anxiety, panic attacks, tremor, and perceptual changes. Withdrawal from higher doses of benzodiazepines can lead to more serious presentations, such as seizures and acute psychosis.⁹ Withdrawal symptoms can develop from discontinuation of the drug and with non-tapered switching between benzodiazepines.¹⁰

Opiates

Opiate withdrawal is an unpleasant experience characterized by generalized pain, nausea and vomiting, sweating, and tachycardia. Neuropsychiatric complaints such as anxiety, agitation, and irritability can also be present. More severe agitation has been described in naltrexone-accelerated detoxification^.11

Cannabis

Recent literature on cannabis use indicates a high prevalence and clinical significance of associated withdrawal symptoms in frequent users. There appear to be two subsets of cannabis withdrawal—one characterized by weakness and hypersomnia, and the other by anxiety, depression, restlessness, and insomnia.¹²

Estrogen

Withdrawal from endogenous estrogen has been hypothesized as a possible cause of puerperal psychosis.¹³ Estrogen withdrawal outside of this setting, however, can and does occur, and recent literature has shown episodes of reversible psychosis associated with the discontinuation of both oral contraceptive regimens and hormonal therapy for menopausal symptoms.

Acute Metabolic Conditions

Hypoglycemia

Hypoglycemia, most often encountered as a side effect of insulin or oral hypoglycemic therapies, is a potentially lethal cause of confusion, anxiety, nervousness, and seizures. Nocturnal hypoglycemia can manifest as nightmares, crying out, and confusion upon awakening. A fingerstick blood-glucose test is an absolutely vital part of the initial work-up of any patient with an altered mental status or overt psychiatric complaint.¹⁴

Central Pontine Myelinolysis

A potentially devastating neurological condition associated with malnourishment and alcohol dependence, central pontine myelinolysis (CPM) is classically exacerbated by rapid overcorrection of hyponatremia. While the disease can manifest primarily with quadriplegia or pseudobulbar palsy and eventual progress to the dreaded “locked-in” syndrome, early presentations can include psychiatric symptoms such as behavioral changes, psychosis, and cognitive disturbances. Patients with early signs and symptoms of CPM have been misdiagnosed as having schizophrenia with catatonia, leading to delayed treatment and poor outcomes. The EP should remain vigilant when evaluating for this condition and consider a magnetic resonance imaging study in patients with psychiatric symptoms in the setting of fluctuating hyponatremia.¹⁵

Autoimmune Disorders

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders, and has a higher incidence in young women. The disease affects multiple organ systems. Though the classic initial presentation of SLE is fever, joint pain, and rash, the associated neuropsychiatric syndromes of this disease are diverse and surprisingly common, and can be the initial manifestation of the disease. Common psychiatric manifestations of SLE include cognitive dysfunction, anxiety, mood disorders such as depression, acute confusion, psychosis, paranoia, and auditory or visual hallucinations.¹⁶

Anti-N-methyl-D-Aspartate Receptor Encephalitis

Initially described as a paraneoplastic effect of ovarian teratomas, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is actually an autoimmune disorder that can occur even in the absence of a primary tumor. As with SLE, the condition primarily occurs in young women. Antibodies in the cerebrospinal fluid cause prominent psychiatric symptoms such as acute psychosis, delusional thinking, hallucinations, agitation, and confusion. Although the disease can progress to seizures, movement disorders, autonomic dysregulation, and ultimately death, early recognition and treatment can lead to positive outcomes in up to 80% of cases.¹⁷ While the prevalence of anti-NMDAR antibodies in new-onset psychosis remains unclear, recent literature has suggested widespread screening for the disease in all first presentations of psychotic episodes.^18,19

Multiple Sclerosis

Multiple sclerosis (MS) is another autoimmune disorder that has a higher prevalence in young women. The disease is characterized by central nervous system involvement that occurs over a period of months to years, with symptoms corresponding to different anatomic locations. Though the classic presenting symptom of MS is optic neuritis, neuropsychiatric syndromes are a common co-occurrence and can be the initial presenting symptom. The most commonly associated psychiatric complaints are anxiety, depression, and bipolar disorder, though case reports of SLE have described acute psychosis, psychotic depression, and adult-onset tic disorder.²⁰

Trauma

Subarachnoid Hemorrhage

Long-term psychiatric sequelae from subarachnoid hemorrhage, either traumatic or aneurysmal, manifest most commonly as personality changes, intellectual impairment, depression, and anxiety. This condition is also known to cause a host of more bizarre psychiatric presentations, such as new-onset kleptomania, akinetic mutism, confabulatory amnesia, acute psychosis, and Capgras syndrome (the delusion that familiar individuals have been replaced by imposters). These symptoms can occur at initial presentation, and may show variable improvement with shunt surgery.²¹

Subdural Hematoma

Acute or chronic subdural hematoma can result from major head trauma, or even quite minor head trauma in an elderly or coagulopathic patient. Some common psychiatric manifestations of subdural hematoma include cognitive impairment, withdrawn behavior, blunted affect otherwise mimicking schizophrenic psychosis, and catatonia. The EP should consider early imaging studies in patients with new-onset psychotic symptoms—especially when they are refractory to typical antipsychotics.²²

Central Nervous Symptom Diseases

Huntington Disease

Huntington disease (HD) is an autosomal dominant inherited, progressive neurodegenerative disorder characterized by mental decline, mood disorder, and muscle coordination problems that eventually become the classic involuntary writhing termed chorea. Due to its progressive nature, precise onset of the disease is difficult to describe; however, HD can manifest initially as schizophrenia-like psychotic episodes with only minimal apparent motor difficulty. Family history, including movement disorders and suicide, is important to obtain when available.²³

Parkinson Disease

A progressive and disabling neurodegenerative disorder, Parkinson disease (PD) is classically characterized by fine resting tremor, cogwheeling rigidity, akinesia and mask-like facies, and postural instability. Comorbidity of psychiatric disorders is high, both as a result of the underlying disease process and as a side effect of dopaminergic treatment regimes. Common presentations of psychiatric disorders in PD include schizophrenia-like psychosis with visual hallucinations and mood disorders with prominent apathy and executive dysfunction. Recognition of the comorbidity is important because psychiatric disorders in PD respond differently to treatment than classic psychiatric disorders.²⁴

Temporal Lobe Epilepsy

Epilepsy is a complex group of related neurological disorders involving unregulated nerve cell firing with a large variability in clinical presentation. Characteristically there is recurrent seizure activity. Temporal lobe epilepsy (TLE) is a subset of epilepsy known to present as a number of behavioral and neuropsychiatric complaints. Most presentations of TLE involve auras of emotional phenomena such as depression, fear, or anxiety, which can occur alone or with subsequent progression to complex partial or secondary generalized seizures.²⁵ Many other bizarre presentations of TLE have been reported, including recurrent, potentially debilitating déjà vu, vivid recollection of past traumatic events mimicking posttraumatic stress disorder, paranoid delusions following olfactory triggers; and unprovoked attacks of depersonalization, derealization, anxiety, and dyspnea originally misdiagnosed as panic attack.

Stroke

The term “stroke chameleon” refers to presentations suggestive of other diseases that actually represent underlying strokes. Altered mental status is by far the largest block of these chameleons, with up to 30% of misdiagnosed strokes being misdiagnosed as altered mental status. The positive predictive value of altered mental status alone (ie, the chance that the diagnosis of altered mental status actually represents an undiagnosed acute stroke) is 7%.²⁶

Case Scenarios Continued

Case 1

[The 58-year-old woman with intermittent chest pain.]

The patient’s D-dimer and troponin I levels were normal. Before the EP had an opportunity to discuss the results and next steps with the patient, the nurse asked him to see the patient immediately. Upon entering her room, the EP noted that the patient appeared anxious. The patient said the shortness of breath had returned, and also that she felt as if she were “floating” off the gurney, outside of her body. A check of her vital signs revealed a heart rate of 106 beats/minute and blood pressure of 160/100 mm Hg. A repeat ECG was significant only for sinus tachycardia. In an effort to calm the patient, the EP reassured her that the ECG, chest X-ray, and screening laboratory studies were normal, and that there was no evidence of a heart attack. Relieved, the patient asked for an Ativan to calm her nerves. Upon further questioning, the patient sheepishly reported that she had been taking 3 to 6 mg lorazepam for about 10 years, as prescribed by her family physician (FP) for anxiety. She further admitted that she abruptly discontinued taking the drug about one week before this ED visit after she’d heard on a daytime TV show that the medication was addictive.

After receiving lorazepam, the patient showed marked improvement. The EP’s final impressions were atypical chest pain and acute panic attack precipitated by abrupt benzodiazepine withdrawal. After discussing the case with the patient’s FP, the EP discharged the patient home with instructions to complete the cardiac evaluation as an outpatient. The EP also recommended that the patient resume taking lorazepam and follow-up with her FP within one week to discuss a benzodiazepine taper and alternative therapy for anxiety.

Case 2

[The 36-year-old woman with altered mental status.]

When the EP entered the patient’s room, he witnessed the patient staring at her husband and striking him repetitively with her right arm. When the EP asked the patient to stop hitting, her husband told the EP that everything was alright and that the patient’s neurologist had previously told them this behavior was caused by a seizure. While in the next examination room, one of the EP’s colleagues had overheard some of the patient’s history and recognized the name of the patient’s neurologist as a specialist in partial complex seizures—one who had retired from the local medical school about 10 years ago.

After records from the local university hospital confirmed the patient’s diagnosis of partial complex seizures, she was given intravenous lorazepam 2 mg; she became alert, conversational, and stopped flailing her right arm. She was then admitted to the hospital for medical stabilization of her frequent seizures.

Editor’s Note: Part 2 of this article will appear in the June 2016 issue of Emergency Medicine and will cover psychiatric presentations related to dementia, cancer, cardiac disease, nutritional deficiencies, endocrine disorders, and toxins.

The chaos of a busy ED can test the cognitive reserve of even the most focused practitioner. To streamline the challenge of serial diagnosis and treatment, clinicians employ heuristics while honing the skills of pattern recognition. However, by definition, heuristics employs shortcuts, leaving out information for the sake of efficiency—sometimes at the expense of accuracy. Whether a patient presents with chest pain, abdominal pain, headache, or (the dreaded) dizziness, emergency physicians (EPs) employ algorithms based on a combination of education and prior experience.

Most of the time, these models lead the EP along the correct path, but not always. For example, when a clinician evaluating a patient presenting with psychotic behavior assumes the patient has schizophrenia, he or she will be correct eight or nine times out of 10. However, in some cases, a patient’s bizarre behavior may not be due to a true psychiatric disorder but, for example, from ingestion of an illicit substance.

In addition, in such patients, psychiatric symptoms may be masking a serious acute, organic condition—one requiring prompt intervention and therapy to avoid morbidity or death. To help prevent diagnostic errors, this 2-part series reviews several of the most common medical mimics of psychiatric conditions. Part 1 of this series reviews the psychiatric presentations associated with medical conditions of an infectious, pharmacological withdrawal, metabolic, autoimmune, traumatic, or central nervous system etiology (Table 1). This article also discusses clinical signs and symptoms that suggest an increased likelihood that a patient’s psychiatric symptoms are from an underlying medical condition (Table 2).

Case Scenarios

Case 1

A 58-year-old woman with a history of smoking 40 packs of cigarettes per year presented to the ED 1 hour after onset of intermittent chest pain. Upon arrival at the ED, the patient stated that she had trouble catching her breath on and off throughout the day. The patient’s vital signs, electrocardiogram (ECG), and chest X-ray were all normal. The physical examination was unremarkable except for mild diaphoresis. The patient denied experiencing palpitations, recent travel, or previous episodes; she further stated that she was currently not on any medications. There was no previous history of visits to this hospital. The patient’s husband, who accompanied her to the ED, noted that his wife’s behavior had been atypical for approximately 1 week.

After receiving aspirin, the patient appeared symptom-free. Pending the results of another chest radiograph and laboratory evaluation, the EP anticipated moving her to the chest-pain observation unit.

Case 2

A 36-year-old woman presented with altered mental status to the ED via emergency medical services (EMS). Her vital signs, including temperature, were normal. Despite intermittently appearing to be asleep, the patient was alternatingly cooperative and combative. She repetitively whispered, “Who am I?” and randomly shouted at staff members as they walked by her room.

Her neurological examination was nonfocal. The hospital’s electronic medical record (EMR) for this patient showed nearly monthly ED visits for behavioral symptoms. Precipitating events noted in the EMR included job loss and separation from her husband. While waiting for the results of the basic laboratory work-up and toxicology screening to medically clear the patient for psychiatric evaluation, the EP contemplated a computed tomography (CT) study. Realizing the patient would not be able to remain still for the scan, the EP ordered 10 mg of intramuscular ziprasidone for sedation. When the patient’s husband arrived, the EP placed the CT scan on hold until she could obtain additional history from him.

Infections

Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is a serious but treatable disease—one that requires early detection and treatment to avoid severe morbidity. While the classic symptoms are fever and altered mental status, recent literature has noted that afebrile patients with HSE may present with behavioral changes, cognitive decline, aggression, and disinhibition. Therefore, diagnosis of a functional psychiatric complaint, if made initially, could delay appropriate treatment with acyclovir.¹

Human Immunodeficiency Virus

Progression of human immunodeficiency virus (HIV) is a well-known cause of various neurocognitive disorders, including early-onset dementia. Since the availability of highly active antiretroviral therapy, the incidence of HIV dementia has decreased, but HIV remains the most common preventable cause of dementia in persons younger than age 50 years. Recent literature has described HIV dementia presenting as an early-onset, rapidly progressing dementia in a young person. Thus, the EP should consider early HIV testing in any young patient who presents with dementia, especially one with a history of fever of unknown origin.²

Progressive Multifocal Encephalopathy

Caused by reactivation of the John Cunningham virus, progressive multifocal encephalopathy has been classically described as a potentially lethal complication of a severely immunocompromised state, often presenting with clumsiness, weakness, visual changes, speech difficulty, and behavioral changes. Though typically described as occurring in the context of acquired immunodeficiency disease syndrome, hematological malignancy, or organ transplant, the condition can occur in the setting of minimal or occult immunosuppression—especially in patients with a history of cirrhosis. If the condition is detected early, immunotherapy can result in significant clinical improvement.³

Syphilis

Late stages of syphilis can present with a wide variety of psychiatric symptoms, including personality disorder, psychosis, delirium, and dementia. As with HIV, there has been a resurgence of syphilis cases, and screening is now often a routine part of a neuropsychiatric work-up. The EP should consider syphilis in the differential for any new-onset psychiatric complaint.^4,5

Typhoid Fever

Although this severe febrile illness is uncommon in the United States, it is endemic to many tropical countries within Africa, Southeast Asia, and Central and South America. Typhoid is characterized by a stepwise fever that can progress to abdominal distension, toxemia, and potentially bowel perforation. It is also known to present with psychiatric symptoms such as acute confusion, psychosis, generalized anxiety disorder, and, though rare, depressive disorder. Physicians traveling to rural endemic areas should be aware of these neuropsychiatric presentations to avoid misdiagnosis and delay of treatment.⁶ Other infectious endemic diseases with reports of neuropsychiatric components are neurocystercercosis, Lyme disease, and African trypanosomiasis.

Pharmacological Withdrawal Syndromes

Alcohol

Alcohol withdrawal is a common presentation in the ED, and up to 24% of US adults brought to the ED by EMS suffer from alcoholism. Typically characterized by tachycardia, hypertension, and tremors, alcohol withdrawal syndrome can also feature psychiatric components such as agitation, hallucinations, persecutory delusions, and even self-mutilation.⁷ Evidence-based protocols indicate loading doses of benzodiazepines as a mainstay of treatment, with supplemental barbiturates or propofol in cases of treatment failure.⁸

Benzodiazepines

Withdrawal from therapeutic doses of benzodiazepines can potentially cause psychiatric symptoms, including sleep disturbances, irritability, anxiety, panic attacks, tremor, and perceptual changes. Withdrawal from higher doses of benzodiazepines can lead to more serious presentations, such as seizures and acute psychosis.⁹ Withdrawal symptoms can develop from discontinuation of the drug and with non-tapered switching between benzodiazepines.¹⁰

Opiates

Opiate withdrawal is an unpleasant experience characterized by generalized pain, nausea and vomiting, sweating, and tachycardia. Neuropsychiatric complaints such as anxiety, agitation, and irritability can also be present. More severe agitation has been described in naltrexone-accelerated detoxification^.11

Cannabis

Recent literature on cannabis use indicates a high prevalence and clinical significance of associated withdrawal symptoms in frequent users. There appear to be two subsets of cannabis withdrawal—one characterized by weakness and hypersomnia, and the other by anxiety, depression, restlessness, and insomnia.¹²

Estrogen

Withdrawal from endogenous estrogen has been hypothesized as a possible cause of puerperal psychosis.¹³ Estrogen withdrawal outside of this setting, however, can and does occur, and recent literature has shown episodes of reversible psychosis associated with the discontinuation of both oral contraceptive regimens and hormonal therapy for menopausal symptoms.

Acute Metabolic Conditions

Hypoglycemia

Hypoglycemia, most often encountered as a side effect of insulin or oral hypoglycemic therapies, is a potentially lethal cause of confusion, anxiety, nervousness, and seizures. Nocturnal hypoglycemia can manifest as nightmares, crying out, and confusion upon awakening. A fingerstick blood-glucose test is an absolutely vital part of the initial work-up of any patient with an altered mental status or overt psychiatric complaint.¹⁴

Central Pontine Myelinolysis

A potentially devastating neurological condition associated with malnourishment and alcohol dependence, central pontine myelinolysis (CPM) is classically exacerbated by rapid overcorrection of hyponatremia. While the disease can manifest primarily with quadriplegia or pseudobulbar palsy and eventual progress to the dreaded “locked-in” syndrome, early presentations can include psychiatric symptoms such as behavioral changes, psychosis, and cognitive disturbances. Patients with early signs and symptoms of CPM have been misdiagnosed as having schizophrenia with catatonia, leading to delayed treatment and poor outcomes. The EP should remain vigilant when evaluating for this condition and consider a magnetic resonance imaging study in patients with psychiatric symptoms in the setting of fluctuating hyponatremia.¹⁵

Autoimmune Disorders

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders, and has a higher incidence in young women. The disease affects multiple organ systems. Though the classic initial presentation of SLE is fever, joint pain, and rash, the associated neuropsychiatric syndromes of this disease are diverse and surprisingly common, and can be the initial manifestation of the disease. Common psychiatric manifestations of SLE include cognitive dysfunction, anxiety, mood disorders such as depression, acute confusion, psychosis, paranoia, and auditory or visual hallucinations.¹⁶

Anti-N-methyl-D-Aspartate Receptor Encephalitis

Initially described as a paraneoplastic effect of ovarian teratomas, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is actually an autoimmune disorder that can occur even in the absence of a primary tumor. As with SLE, the condition primarily occurs in young women. Antibodies in the cerebrospinal fluid cause prominent psychiatric symptoms such as acute psychosis, delusional thinking, hallucinations, agitation, and confusion. Although the disease can progress to seizures, movement disorders, autonomic dysregulation, and ultimately death, early recognition and treatment can lead to positive outcomes in up to 80% of cases.¹⁷ While the prevalence of anti-NMDAR antibodies in new-onset psychosis remains unclear, recent literature has suggested widespread screening for the disease in all first presentations of psychotic episodes.^18,19

Multiple Sclerosis

Multiple sclerosis (MS) is another autoimmune disorder that has a higher prevalence in young women. The disease is characterized by central nervous system involvement that occurs over a period of months to years, with symptoms corresponding to different anatomic locations. Though the classic presenting symptom of MS is optic neuritis, neuropsychiatric syndromes are a common co-occurrence and can be the initial presenting symptom. The most commonly associated psychiatric complaints are anxiety, depression, and bipolar disorder, though case reports of SLE have described acute psychosis, psychotic depression, and adult-onset tic disorder.²⁰

Trauma

Subarachnoid Hemorrhage

Long-term psychiatric sequelae from subarachnoid hemorrhage, either traumatic or aneurysmal, manifest most commonly as personality changes, intellectual impairment, depression, and anxiety. This condition is also known to cause a host of more bizarre psychiatric presentations, such as new-onset kleptomania, akinetic mutism, confabulatory amnesia, acute psychosis, and Capgras syndrome (the delusion that familiar individuals have been replaced by imposters). These symptoms can occur at initial presentation, and may show variable improvement with shunt surgery.²¹

Subdural Hematoma

Acute or chronic subdural hematoma can result from major head trauma, or even quite minor head trauma in an elderly or coagulopathic patient. Some common psychiatric manifestations of subdural hematoma include cognitive impairment, withdrawn behavior, blunted affect otherwise mimicking schizophrenic psychosis, and catatonia. The EP should consider early imaging studies in patients with new-onset psychotic symptoms—especially when they are refractory to typical antipsychotics.²²

Central Nervous Symptom Diseases

Huntington Disease

Huntington disease (HD) is an autosomal dominant inherited, progressive neurodegenerative disorder characterized by mental decline, mood disorder, and muscle coordination problems that eventually become the classic involuntary writhing termed chorea. Due to its progressive nature, precise onset of the disease is difficult to describe; however, HD can manifest initially as schizophrenia-like psychotic episodes with only minimal apparent motor difficulty. Family history, including movement disorders and suicide, is important to obtain when available.²³

Parkinson Disease

A progressive and disabling neurodegenerative disorder, Parkinson disease (PD) is classically characterized by fine resting tremor, cogwheeling rigidity, akinesia and mask-like facies, and postural instability. Comorbidity of psychiatric disorders is high, both as a result of the underlying disease process and as a side effect of dopaminergic treatment regimes. Common presentations of psychiatric disorders in PD include schizophrenia-like psychosis with visual hallucinations and mood disorders with prominent apathy and executive dysfunction. Recognition of the comorbidity is important because psychiatric disorders in PD respond differently to treatment than classic psychiatric disorders.²⁴

Temporal Lobe Epilepsy

Epilepsy is a complex group of related neurological disorders involving unregulated nerve cell firing with a large variability in clinical presentation. Characteristically there is recurrent seizure activity. Temporal lobe epilepsy (TLE) is a subset of epilepsy known to present as a number of behavioral and neuropsychiatric complaints. Most presentations of TLE involve auras of emotional phenomena such as depression, fear, or anxiety, which can occur alone or with subsequent progression to complex partial or secondary generalized seizures.²⁵ Many other bizarre presentations of TLE have been reported, including recurrent, potentially debilitating déjà vu, vivid recollection of past traumatic events mimicking posttraumatic stress disorder, paranoid delusions following olfactory triggers; and unprovoked attacks of depersonalization, derealization, anxiety, and dyspnea originally misdiagnosed as panic attack.

Stroke

The term “stroke chameleon” refers to presentations suggestive of other diseases that actually represent underlying strokes. Altered mental status is by far the largest block of these chameleons, with up to 30% of misdiagnosed strokes being misdiagnosed as altered mental status. The positive predictive value of altered mental status alone (ie, the chance that the diagnosis of altered mental status actually represents an undiagnosed acute stroke) is 7%.²⁶

Case Scenarios Continued

Case 1

[The 58-year-old woman with intermittent chest pain.]

The patient’s D-dimer and troponin I levels were normal. Before the EP had an opportunity to discuss the results and next steps with the patient, the nurse asked him to see the patient immediately. Upon entering her room, the EP noted that the patient appeared anxious. The patient said the shortness of breath had returned, and also that she felt as if she were “floating” off the gurney, outside of her body. A check of her vital signs revealed a heart rate of 106 beats/minute and blood pressure of 160/100 mm Hg. A repeat ECG was significant only for sinus tachycardia. In an effort to calm the patient, the EP reassured her that the ECG, chest X-ray, and screening laboratory studies were normal, and that there was no evidence of a heart attack. Relieved, the patient asked for an Ativan to calm her nerves. Upon further questioning, the patient sheepishly reported that she had been taking 3 to 6 mg lorazepam for about 10 years, as prescribed by her family physician (FP) for anxiety. She further admitted that she abruptly discontinued taking the drug about one week before this ED visit after she’d heard on a daytime TV show that the medication was addictive.

After receiving lorazepam, the patient showed marked improvement. The EP’s final impressions were atypical chest pain and acute panic attack precipitated by abrupt benzodiazepine withdrawal. After discussing the case with the patient’s FP, the EP discharged the patient home with instructions to complete the cardiac evaluation as an outpatient. The EP also recommended that the patient resume taking lorazepam and follow-up with her FP within one week to discuss a benzodiazepine taper and alternative therapy for anxiety.

Case 2

[The 36-year-old woman with altered mental status.]

When the EP entered the patient’s room, he witnessed the patient staring at her husband and striking him repetitively with her right arm. When the EP asked the patient to stop hitting, her husband told the EP that everything was alright and that the patient’s neurologist had previously told them this behavior was caused by a seizure. While in the next examination room, one of the EP’s colleagues had overheard some of the patient’s history and recognized the name of the patient’s neurologist as a specialist in partial complex seizures—one who had retired from the local medical school about 10 years ago.

After records from the local university hospital confirmed the patient’s diagnosis of partial complex seizures, she was given intravenous lorazepam 2 mg; she became alert, conversational, and stopped flailing her right arm. She was then admitted to the hospital for medical stabilization of her frequent seizures.

Editor’s Note: Part 2 of this article will appear in the June 2016 issue of Emergency Medicine and will cover psychiatric presentations related to dementia, cancer, cardiac disease, nutritional deficiencies, endocrine disorders, and toxins.

The ability of the United States to respond to a potential spike in Zika virus infection rates is a cause for concern, according to a top federal health official.

“The big question is will we get local transmission, and my response to that is very likely we will,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters during a joint media briefing with the Pan American Health Organization (PAHO) on May 3.

As many as 500 million people in the Americas are at risk for being infected by the Zika virus, PAHO’s Zika incident manager, Dr. Sylvain Aldighieri, said during the briefing.

In the continental United States to date, there have been about 400 travel-related cases of infection. In Puerto Rico, there have been nearly 700 locally reported cases, and one Zika-related death.

Countries at highest risk for Zika include those that have experienced any outbreaks of dengue fever or chikungunya in the past 15 years, Dr. Aldighieri said. Hawaii and U.S. territories in the Caribbean have experienced local dengue outbreaks during that time. Florida has had local outbreaks of both illnesses.

In the United States, Zika is poised to gain a stronger foothold even as funding for the study and prevention of the virus remains stalled in Congress, and a lack of cohesive public health messaging leaves the public vulnerable to misunderstanding the potential threat of the disease, according to Dr. Fauci.

A vaccine to fight Zika virus is currently under development. “Don’t confuse that with readiness,” Dr. Fauci cautioned.

Dr. Fauci said he believes the disbursement by Congress of President Obama’s requested $1.9 billion in Zika-related funds would facilitate a more comprehensive approach to preventing and treating the virus’s spread, but so far, the funding remains stalled.

As a result, Dr. Fauci said he has reallocated funds intended for other infectious disease research needs to cover Zika-related costs, but is concerned that continued congressional inaction could mean he is left with holes across many budgets. “That 1.9 billion dollars is essential,” he said.

Vaccine progress

In April, $589 millionin funds primarily earmarked for the Ebola crisis were redirected by the Obama administration to fight the Zika virus. That money is now being used in part to fund development of a vaccine that is expected to be ready for a phase I study of 80 people by September 2016. If successful, a phase II-b efficacy study of the vaccine would be conducted in the first quarter of 2017 in a country or region that has a high rate of infection.

Dr. Fauci said that although the study is not be as high-powered as would be ideal, researchers might be able to determine the vaccine’s efficacy with several thousand volunteers, taking into consideration that during the 1-3 years needed to gather conclusive data, herd immunity could skew rates of infection downward, bringing into question the vaccine’s actual efficacy.

“That’s just something we have to deal with,” Dr. Fauci said, saying that fewer people being infected is a good thing, either way.

Research gaps

Other pressing Zika research needs to include learning more about the virus’s impact on a developing fetus.

“We don’t know exactly what the percentage is of [infants born with] microcephaly,” Dr. Fauci said. “We don’t know beyond microcephaly what the long-range effects are on babies that look like they were born [without microcephaly] but might have other defects that are more subtle.”

Dr. Fauci said current data are unhelpful in that they show anywhere from 1% to 29% of infected mothers will give birth to children with congenital defects. However, he said that a coalition of nations affected by the virus is currently enrolling thousands of pregnant women in a cohort study to determine risk ratios.

“When we get the data from that study, we will be able to answer precisely what the percentage is, but today in May 2016, we don’t know the answer,” he said.

Predicting which infants are most susceptible, and at what point in utero abnormalities develop, are questions still under investigation, although a study published earlier this year supports the theory that infection during the first trimester poses the highest risk to a developing fetus.

Communicating risk

Another problem facing health officials is how to communicate the potential seriousness of an illness that, if it presents at all, does so only mildly, Dr. Fauci said. “In general, it’s a disease in which 80% of people don’t have any symptoms.”

The World Health Organization advises physicians to suspect Zika – particularly if a person has been in Zika-affected regions – if clinical symptoms include rash, fever, or both, plus at least one of these: arthralgia, arthritis, or conjunctivitis. Aside from bed rest, hydration, and over-the-counter analgesics, there are no specific treatments for the virus.

How to counsel women about avoiding pregnancy where Zika is a concern also poses challenges, particularly if the pregnancy is unintended, as about half of all American pregnancies are, or if, as Dr. Fauci told reporters, pregnancy is “guided by laws and religion.”

Although federal policy has not been to advise persons about whether to delay pregnancy, Dr. Fauci said U.S. officials are unwilling to contradict authorities in local regions such as Puerto Rico where such statements have been issued.

On April 28, the Food and Drug Administration authorized the emergency use of a commercial in vitro diagnostic test for use in individuals with symptoms of the virus, or those who have traveled to affected regions. Earlier this year, the FDA granted emergency authorization for use of a single test that can detect Zika, dengue, and chikungunya. Still, serology tests for Zika are often inconclusive, since the virus can mimic dengue or chikungunya, according to Dr. Aldighieri. “It can be complex to know if there is a Zika or dengue or chikungunya outbreak,” he said.

[email protected]

On Twitter @whitneymcknight

The ability of the United States to respond to a potential spike in Zika virus infection rates is a cause for concern, according to a top federal health official.

“The big question is will we get local transmission, and my response to that is very likely we will,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters during a joint media briefing with the Pan American Health Organization (PAHO) on May 3.

As many as 500 million people in the Americas are at risk for being infected by the Zika virus, PAHO’s Zika incident manager, Dr. Sylvain Aldighieri, said during the briefing.

In the continental United States to date, there have been about 400 travel-related cases of infection. In Puerto Rico, there have been nearly 700 locally reported cases, and one Zika-related death.

Countries at highest risk for Zika include those that have experienced any outbreaks of dengue fever or chikungunya in the past 15 years, Dr. Aldighieri said. Hawaii and U.S. territories in the Caribbean have experienced local dengue outbreaks during that time. Florida has had local outbreaks of both illnesses.

In the United States, Zika is poised to gain a stronger foothold even as funding for the study and prevention of the virus remains stalled in Congress, and a lack of cohesive public health messaging leaves the public vulnerable to misunderstanding the potential threat of the disease, according to Dr. Fauci.

A vaccine to fight Zika virus is currently under development. “Don’t confuse that with readiness,” Dr. Fauci cautioned.

Dr. Fauci said he believes the disbursement by Congress of President Obama’s requested $1.9 billion in Zika-related funds would facilitate a more comprehensive approach to preventing and treating the virus’s spread, but so far, the funding remains stalled.

As a result, Dr. Fauci said he has reallocated funds intended for other infectious disease research needs to cover Zika-related costs, but is concerned that continued congressional inaction could mean he is left with holes across many budgets. “That 1.9 billion dollars is essential,” he said.

Vaccine progress

In April, $589 millionin funds primarily earmarked for the Ebola crisis were redirected by the Obama administration to fight the Zika virus. That money is now being used in part to fund development of a vaccine that is expected to be ready for a phase I study of 80 people by September 2016. If successful, a phase II-b efficacy study of the vaccine would be conducted in the first quarter of 2017 in a country or region that has a high rate of infection.

Dr. Fauci said that although the study is not be as high-powered as would be ideal, researchers might be able to determine the vaccine’s efficacy with several thousand volunteers, taking into consideration that during the 1-3 years needed to gather conclusive data, herd immunity could skew rates of infection downward, bringing into question the vaccine’s actual efficacy.

“That’s just something we have to deal with,” Dr. Fauci said, saying that fewer people being infected is a good thing, either way.

Research gaps

Other pressing Zika research needs to include learning more about the virus’s impact on a developing fetus.

“We don’t know exactly what the percentage is of [infants born with] microcephaly,” Dr. Fauci said. “We don’t know beyond microcephaly what the long-range effects are on babies that look like they were born [without microcephaly] but might have other defects that are more subtle.”

Dr. Fauci said current data are unhelpful in that they show anywhere from 1% to 29% of infected mothers will give birth to children with congenital defects. However, he said that a coalition of nations affected by the virus is currently enrolling thousands of pregnant women in a cohort study to determine risk ratios.

“When we get the data from that study, we will be able to answer precisely what the percentage is, but today in May 2016, we don’t know the answer,” he said.

Predicting which infants are most susceptible, and at what point in utero abnormalities develop, are questions still under investigation, although a study published earlier this year supports the theory that infection during the first trimester poses the highest risk to a developing fetus.

Communicating risk

Another problem facing health officials is how to communicate the potential seriousness of an illness that, if it presents at all, does so only mildly, Dr. Fauci said. “In general, it’s a disease in which 80% of people don’t have any symptoms.”

The World Health Organization advises physicians to suspect Zika – particularly if a person has been in Zika-affected regions – if clinical symptoms include rash, fever, or both, plus at least one of these: arthralgia, arthritis, or conjunctivitis. Aside from bed rest, hydration, and over-the-counter analgesics, there are no specific treatments for the virus.

How to counsel women about avoiding pregnancy where Zika is a concern also poses challenges, particularly if the pregnancy is unintended, as about half of all American pregnancies are, or if, as Dr. Fauci told reporters, pregnancy is “guided by laws and religion.”

Although federal policy has not been to advise persons about whether to delay pregnancy, Dr. Fauci said U.S. officials are unwilling to contradict authorities in local regions such as Puerto Rico where such statements have been issued.

On April 28, the Food and Drug Administration authorized the emergency use of a commercial in vitro diagnostic test for use in individuals with symptoms of the virus, or those who have traveled to affected regions. Earlier this year, the FDA granted emergency authorization for use of a single test that can detect Zika, dengue, and chikungunya. Still, serology tests for Zika are often inconclusive, since the virus can mimic dengue or chikungunya, according to Dr. Aldighieri. “It can be complex to know if there is a Zika or dengue or chikungunya outbreak,” he said.

[email protected]

On Twitter @whitneymcknight

The ability of the United States to respond to a potential spike in Zika virus infection rates is a cause for concern, according to a top federal health official.

“The big question is will we get local transmission, and my response to that is very likely we will,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told reporters during a joint media briefing with the Pan American Health Organization (PAHO) on May 3.

As many as 500 million people in the Americas are at risk for being infected by the Zika virus, PAHO’s Zika incident manager, Dr. Sylvain Aldighieri, said during the briefing.

In the continental United States to date, there have been about 400 travel-related cases of infection. In Puerto Rico, there have been nearly 700 locally reported cases, and one Zika-related death.

Countries at highest risk for Zika include those that have experienced any outbreaks of dengue fever or chikungunya in the past 15 years, Dr. Aldighieri said. Hawaii and U.S. territories in the Caribbean have experienced local dengue outbreaks during that time. Florida has had local outbreaks of both illnesses.

In the United States, Zika is poised to gain a stronger foothold even as funding for the study and prevention of the virus remains stalled in Congress, and a lack of cohesive public health messaging leaves the public vulnerable to misunderstanding the potential threat of the disease, according to Dr. Fauci.

A vaccine to fight Zika virus is currently under development. “Don’t confuse that with readiness,” Dr. Fauci cautioned.

Dr. Fauci said he believes the disbursement by Congress of President Obama’s requested $1.9 billion in Zika-related funds would facilitate a more comprehensive approach to preventing and treating the virus’s spread, but so far, the funding remains stalled.

As a result, Dr. Fauci said he has reallocated funds intended for other infectious disease research needs to cover Zika-related costs, but is concerned that continued congressional inaction could mean he is left with holes across many budgets. “That 1.9 billion dollars is essential,” he said.

Vaccine progress

In April, $589 millionin funds primarily earmarked for the Ebola crisis were redirected by the Obama administration to fight the Zika virus. That money is now being used in part to fund development of a vaccine that is expected to be ready for a phase I study of 80 people by September 2016. If successful, a phase II-b efficacy study of the vaccine would be conducted in the first quarter of 2017 in a country or region that has a high rate of infection.

Dr. Fauci said that although the study is not be as high-powered as would be ideal, researchers might be able to determine the vaccine’s efficacy with several thousand volunteers, taking into consideration that during the 1-3 years needed to gather conclusive data, herd immunity could skew rates of infection downward, bringing into question the vaccine’s actual efficacy.

“That’s just something we have to deal with,” Dr. Fauci said, saying that fewer people being infected is a good thing, either way.

Research gaps

Other pressing Zika research needs to include learning more about the virus’s impact on a developing fetus.

“We don’t know exactly what the percentage is of [infants born with] microcephaly,” Dr. Fauci said. “We don’t know beyond microcephaly what the long-range effects are on babies that look like they were born [without microcephaly] but might have other defects that are more subtle.”

Dr. Fauci said current data are unhelpful in that they show anywhere from 1% to 29% of infected mothers will give birth to children with congenital defects. However, he said that a coalition of nations affected by the virus is currently enrolling thousands of pregnant women in a cohort study to determine risk ratios.

“When we get the data from that study, we will be able to answer precisely what the percentage is, but today in May 2016, we don’t know the answer,” he said.

Predicting which infants are most susceptible, and at what point in utero abnormalities develop, are questions still under investigation, although a study published earlier this year supports the theory that infection during the first trimester poses the highest risk to a developing fetus.

Communicating risk

Another problem facing health officials is how to communicate the potential seriousness of an illness that, if it presents at all, does so only mildly, Dr. Fauci said. “In general, it’s a disease in which 80% of people don’t have any symptoms.”

The World Health Organization advises physicians to suspect Zika – particularly if a person has been in Zika-affected regions – if clinical symptoms include rash, fever, or both, plus at least one of these: arthralgia, arthritis, or conjunctivitis. Aside from bed rest, hydration, and over-the-counter analgesics, there are no specific treatments for the virus.

How to counsel women about avoiding pregnancy where Zika is a concern also poses challenges, particularly if the pregnancy is unintended, as about half of all American pregnancies are, or if, as Dr. Fauci told reporters, pregnancy is “guided by laws and religion.”

Although federal policy has not been to advise persons about whether to delay pregnancy, Dr. Fauci said U.S. officials are unwilling to contradict authorities in local regions such as Puerto Rico where such statements have been issued.

On April 28, the Food and Drug Administration authorized the emergency use of a commercial in vitro diagnostic test for use in individuals with symptoms of the virus, or those who have traveled to affected regions. Earlier this year, the FDA granted emergency authorization for use of a single test that can detect Zika, dengue, and chikungunya. Still, serology tests for Zika are often inconclusive, since the virus can mimic dengue or chikungunya, according to Dr. Aldighieri. “It can be complex to know if there is a Zika or dengue or chikungunya outbreak,” he said.

[email protected]

On Twitter @whitneymcknight

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.