Epistaxis is a common presenting complaint in family medicine. Successful treatment requires knowledge of nasal anatomy, possible causes, and a step-wise approach.

Epistaxis predominantly affects children between the ages of 2 and 10 years and older adults between the ages of 45 and 65.^1-4 Many presentations are spontaneous and self-limiting; often all that is required is proper first aid. It is important, however, to recognize the signs and symptoms that are suggestive of more worrisome conditions.

Management of epistaxis requires good preparation, appropriate equipment, and adequate assistance. If any of these are lacking, prompt nasal packing followed by referral to an emergency department or ear, nose, and throat (ENT) service is recommended.

Anatomy of the nasal cavity

The nasal cavity has a rich and highly varied blood supply arising from the internal and external carotid arteries with multiple anastomoses and a crossover between the left and right arterial systems.^2,4,5 The internal maxillary artery (IMAX) supplies 80% of the nasal vault.² The sphenopalatine artery (SPA) supplies most of the nasal septum and the turbinates, while the greater palatine artery (GPA) supplies the floor of the nasal septum.^3,5 The ethmoidal arteries course through the cribriform plate to supply the roof of the nasal cavity. The ethmoidal arteries communicates with branches of the SPA posteriorly and several branches anteriorly (FIGURE 1).

Kiesselbach’s plexus is a highly vascularized region of cartilaginous nasal septum anteroinferiorly that is also known as Little’s area. It is supplied by the SPA, GPA, superior labial artery, and ethmoidal arteries.⁵ Woodruff’s plexus is the richly vascularized posterior aspect of the nasal cavity primarily supplied by the SPA.^3,5

Is the bleed anterior or posterior; primary or secondary?

Epistaxis is classified as anterior or posterior based on the arterial supply and the location of the bleed in relation to the piriform aperture.^2,3 Anterior epistaxis occurs in >90% of patients and arises in Little’s area.⁶ Posterior epistaxis arises from Woodruff’s plexus in the posterior nasal septum or lateral nasal wall. It occurs in 5% to 10% of patients, is usually arterial in origin, and leads to a greater risk of airway compromise, aspiration, and difficulty in controlling the hemorrhage.^2,6

Epistaxis can be classified further as primary or secondary hemorrhage. Primary epistaxis is idiopathic, spontaneous bleeds without any precipitants.² Blood vessels within the nasal mucosa run superficially and are relatively unprotected. Damage to this mucosa and to vessel walls can result in bleeding.⁴ Spontaneous rupture of vessels may occur occasionally, during, say the Valsalva maneuver or when straining to lift heavy objects.⁴ Secondary epistaxis occurs when there is a clear and definite cause (eg trauma, anticoagulant use, or surgery).

Continue to: Numerous causes...

Epistaxis can be caused by local, systemic, or environmental factors; medications; or be idiopathic in nature (TABLE 1²). It commonly arises due to self-inflicted trauma from nose picking, particularly in children; trauma to nasal bones or septum; and mucosal irritation from topical nasal drugs, such as corticosteroids and antihistamines. Other local factors include septal abnormalities, such as septal perforation, inflammatory diseases, rhinosinusitis, illicit drug use (eg cocaine), iatrogenic causes, and neoplasia.

Red flags for neoplasia include unilateral or asymmetric symptoms, such as nasal blockage, facial pain, rhinorrhea, headaches, facial swelling or deformity, and cranial neuropathies (ie, facial numbness or double vision). Other red flags include Southeast Asian origin (nasopharyngeal carcinoma), loose maxillary teeth, and deep otalgia (TABLE 2²). In adolescent males, it is important to consider juvenile nasopharyngeal angiofibroma, a benign tumor that can bleed extensively.

Systemic factors include age, hypertension, alcohol use, acquired coagulopathies due to liver or renal disease, hematologic abnormalities, circadian rhythms, and genetic disorders such as hereditary hemorrhagic telangiectasia (HHT), hemophilia, and von Willebrand’s disease.²

Medications that contribute to epistaxis include antiplatelet agents, such as aspirin and clopidogrel; nonsteroidal anti-inflammatory drugs (NSAIDs); warfarin and novel oral anticoagulants (NOACs); and complementary and alternative medicines, such garlic, gingko, and ginseng. Environmental factors include temperature and humidity.²

Ask about trauma, but also about upper GI hemorrhage

Resuscitation and control of bleeding (which we’ll discuss in a moment) should always take priority. A thorough history and examination are also essential. It’s important to elicit details of the acute episode and any previous episodes, including the duration, severity, frequency, laterality of bleed, and contributing or inciting factors.^1,2 Posterior epistaxis often occurs from both nostrils and feels as though blood is dripping down the throat rather than the nose.

Continue to: Hematemesis and melena from upper gastrointestinal hemorrhage...

Hematemesis and melena from upper gastrointestinal hemorrhage can often be overlooked. Elicit history of local trauma, including nose picking, possible foreign body (particularly batteries in children), and recurrent upper respiratory tract infections.

Treatments, including methods previously used to control episodes, can be instructive. Pinching over the nasal bones—rather than the soft cartilaginous part of the nose—unfortunately remains relatively common. Ask about any past medical history that can give clues to the cause of bleeding, such as hypertension, hepatic impairment, easy bruising, family history of coagulation disorders, and social history including alcohol intake, smoking, and recreational drug use—particularly cocaine use. A detailed medication history, as discussed earlier, is vital.

Initial management: Digital pressure

Epistaxis is potentially a life-threatening event. All patients who are actively bleeding require full assessment, resuscitation, and control of the bleeding.⁴ To protect the airway sit the patient upright and lean them forward to prevent aspiration of blood posteriorly into the pharynx. To control bleeding, get the patient to apply digital pressure at the cartilaginous part of the nose for a minimum of 10 minutes. This provides tamponade of the anterior septal vessels. Applying ice packs around the neck and having the patient suck on ice significantly reduces nasal mucosa blood flow and can slow down the bleeding.⁷

If there is significant bleeding

Monitor the patient’s vital signs, in particular, the pulse and respiratory rate. Assess the patient’s hemodynamic stability and look for signs of shock, such as sweating and pallor. Insert 2 large-bore (16 G) intravenous cannula and draw blood for type and crossmatch for potential transfusion if significant bleeding has occurred, in high risk patients (eg patients who are elderly or anticoagulated or have a suspected bleeding diathesis), or if further bleeding is likely to occur.²

Consider fluid resuscitation with intravenous saline initially and blood transfusions based on hemoglobin level, symptoms, and history of ischemic heart disease.^3,6 Routine clotting studies need to be performed if there is a suspected bleeding diathesis or the patient is anticoagulated. Test for hepatic or renal dysfunction in patients with systemic conditions that could lead to coagulopathy. The clinical state of an elderly patient may deteriorate rapidly, so aggressive resuscitation is vital.⁴

Continue to: Getting a better look requires the proper equipment

Universal precautions including facemask, eye protection, and gloves should be worn. Have equipment easily accessible, including sufficient lighting and suction. A headlight enables the use of both hands to assess and treat the patient. The nasal cavity often is obscured by clots, so ask the patient to blow and clear their nose. Although this may lead to a recurrence of bleeding, it could assist in identifying the bleeding point.²

Local anesthetic with a vasoconstrictor should be applied to the nasal mucosa over Little’s area either via a solution applied on cotton-tipped applicator or as a nasal spray. Once adequate local anesthesia is achieved, the nasal cavity can be examined and treatment instigated to stem the hemorrhage. Perform anterior rhinoscopy with a Thudicum’s speculum with one hand (FIGURE 2) while suctioning simultaneously with the other. Assess the nasal cavity systematically, paying particular attention to the septum and Little’s area for an anterior bleed. Look for scabbed and excoriated areas.

Anterior bleeds can be managed safely in primary care, provided that appropriate equipment is available. Consider transfer to an emergency department or referral to an ENT specialist if bleeding continues or if a posterior bleed is suspected.² Examination of the entire nasal cavity via nasendoscopy may be required to identify the source of bleeding—especially with posterior bleeds.

Nonsurgical management

Topical agents

Topical vasoconstrictor and local anaesthetic agents are widely available, and their limited adverse effect profiles make them a convenient first-line therapy.^6,8 These agents reduce hemorrhage to allow for better visualization and analgesia for possible cautery or nasal packing.² Common preparations include cophenylcaine (topical 5% lidocaine solution with 0.5% phenylephrine) and lidocaine injection (0.5%, 1%, or 2%) with epinephrine 1 in 200,000 and cocaine topical solutions (2% or 5%). Topical tranexamic acid has shown significant benefits in acute epistaxis in a systematic review.⁹

Cautery

If direct pressure and medical therapy fail to stop the bleeding, cautery or nasal packing can be performed.^2,8 Chemical cautery entails application of 75% silver nitrate sticks to the bleeding point with firm pressure for 5 to 10 seconds to produce a local chemical burn.⁴ Only one side of the septum should be cauterized, as there is a small risk of septal perforation resulting from decreased vascularization to the septal cartilage.^2,4,8 This can be performed at 4 to 6 week intervals. Electric bipolar cautery with a metal loop is performed by otolaryngologists under local anesthesia.⁴ Compared with electric cautery, silver nitrate cautery is cheap, readily available, easy to perform, equal in effectiveness, and has fewer complications.¹⁰

Continue to: Nasal packing...

Nasal packing

Nasal packing can be performed if cautery is unsuccessful in controlling the bleed or if no bleeding point is seen on examination.² It provides direct mechanical compression and acts as a platelet aggregator, thereby facilitating coagulation.

Anterior packing. Packs should be directed posteriorly along the floor of the nasal cavity, rather than superiorly.² After packing, examine the patient for ongoing bleeding from the contralateral nares or posteriorly in the oropharynx using a tongue depressor. If bleeding is seen, consider packing the other side before removal of the already inserted pack to increase the tamponade pressure over the septum.⁴

Anterior packs are effective, easy to use, widely available, and inexpensive.⁸ Types of packs include traditional packing, nasal tampons, and absorbable packing materials.

The Rapid Rhino is also an option. It’s an inflatable balloon pack coated with a lubricating compound. It remains in contact with the mucosa when deflated and can be left in situ for up to 4 days (FIGURE 3). It has the same rate of control of epistaxis when compared with polyvinyl alcohol. Both patients and physicians found insertion and removal of the Rapid Rhino easier with less patient discomfort.^11-13

Absorbable packs do not require formal removal and are useful for patients with or without coagulopathies. They can be applied topically with a syringe that conforms to the 3-dimensional structure of the nasal cavity.¹ The decision regarding which product to use is based on availability, cost, and physician preference.

Continue to: Posterior packing...

Posterior packing may be required if epistaxis continues despite anterior packing and may take the form of a balloon or a formal pack. A Foley catheter inflated with 3 to 4 mL of water or air is inserted through the anterior nares, along the floor of the nasal cavity into the posterior pharynx and pulled forward until the balloon engages the posterior choana (FIGURE 4). This provides local tamponade and tamponade at the sphenopalatine foramen.^2,4 The balloon is held firmly in place with an umbilical clamp at the anterior nares. To prevent pressure necrosis, the columella can be protected with a soft dressing that is regularly checked by the nursing staff. The nasal cavity is then packed anteriorly with ribbon gauze or a nasal sponge to stem any potential anterior bleeds.

Potential complications include posterior displacement of the balloon with potential airway compromise, deflation in situ, and rupture of the balloon—which could result in aspiration.⁴ It is important to note the Foley catheter is, in fact, not licensed for nasal use.⁴ Insertion only should be performed by a clinician who has been trained in this skill.

Traditional nasopharyngeal packs are rolled gauze attached to tapes or sutured to a catheter. Compared with balloons, they were found to be more effective in controlling epistaxis and produce less short- and long-term complications.² However, they are rather uncomfortable and hence normally performed under general anesthesia.⁴ Posterior packing has many disadvantages. They have a 50% failure rate, which increases to 70% in patients with bleeding disorders.⁸

Complications vary from mild and self-limiting such as infection, hemorrhage, and pressure effects to severe such as toxic shock syndrome, myocardial infarction, and death (TABLE 3^2-4,6,8). There is little evidence supporting the use of prophylactic oral antibiotics after packing. Prophylactic antibiotics are reserved for those with posterior packs or if packs remain in situ for more than 24 hours.⁶

Warm water irrigation

Warm water irrigation via Foley catheter has a reported 82% success rate.⁸ It results in earlier discharge, less pain, less trauma to the nose, and reduced hospital length of stay.¹³ The balloon catheter is used to close off the posterior choana and water irrigation is applied at 45° C to 50° C for about 3 minutes with the help of a caloric stimulator.^4,8 It helps clear blood clots from the nose and reduces local blood flow by causing mucosal edema, which compresses the bleeding vessels.

Continue to: Surgical management

Any bleeding that fails to stop, despite an escalation of management, requires surgical intervention. This includes cases in which the bleeding continues after pack removal.⁴ Options include⁴:

• Diathermy, with bipolar or radiofrequency laser, can be used to localize the bleeding site.
• Septoplasty allows for better access to the nasal cavity, reduction of blood flow to the nasal mucosa by raising a mucoperichondrial flap, correction of a deviated septum, and removal of a septal spur that may be responsible for the epistaxis.
• Arterial ligation involves identification of the bleeding vessel that is clipped or coagulated with bipolar diathermy.
• Endoscopic SPA ligation is an excellent, well-tolerated, and cost-effective method of treating recurrent epistaxis.^6,14 It controls 98% of posterior epistaxis, and is superior to posterior nasal packing and embolization.^2,3,10 It results in a shorter hospital stay, reduction in repeated hemorrhage and painful packing procedures, and a cost saving of >$7,000 per patient if performed early.⁷ Concomitant ligation of the anterior ethmoidal artery may be performed in traumatic epistaxis or when severe bleeding is from the ethmoidal region.^4,6
• Ligation of the IMAX and external carotid arteries is performed rarely due to potential complications and high failure rates.

Arterial embolization

When arterial ligation fails, or is not possible due to anesthetic concerns, selective embolization of the maxillary or facial arteries by specialist radiologists can be considered.⁶ Access to the vascular system through a femoral punch leads to identification of the bleeding point. A catheter is then placed in the artery and the bleeding vessel is embolized. Possible candidates include patients with HHT, bleeding tumors, poor surgical candidates, or patient preference.³

Other management considerations

Once bleeding is controlled, factors that contributed to the epistaxis should be addressed.³ Hypertension needs to be managed. Antiplatelet or anticoagulant therapy may need to be temporarily halted in consultation with specialist physicians. Local treatments such as cautery are unlikely to be effective in patients who are anticoagulated. Nasal packing with a ‘procoagulant’ dressing, such as Kaltostat or Rapid Rhino, is often required.

Patient education and follow-up

Patients should be started on saline sprays or irrigation to maintain nasal hygiene after acute epistaxis. It’s a good idea to teach patients about proper first aid for recurrence (eg, sitting upright with digital pressure applied to the cartilaginous part of the nose, ice packs around the neck and ice to suck) and to encourage them to refrain from activities that may stimulate bleeding (blowing or picking the nose, heavy lifting, strenuous exercise). Also advise patients to abstain from alcohol and hot drinks that cause vasodilatation of nasal vessels as much as possible.⁴ Advise patients that topical gels, lotions, and ointments such as kenacomb, nasalate, or paraffin can be used to moisturise the mucosa and promote healing.¹

All patients with a history of severe or recurrent epistaxis require formal examination of the nasal cavity to rule out a neoplastic lesion.

CORRESPONDENCE
Amy Wong, BMBS, Department ENT/Head and Neck Surgery, Monash ENT Building, PO Box 72, Rear 867 Centre Road, Bentleigh East 3165 Australia, [email protected].

Epistaxis is a common presenting complaint in family medicine. Successful treatment requires knowledge of nasal anatomy, possible causes, and a step-wise approach.

Epistaxis predominantly affects children between the ages of 2 and 10 years and older adults between the ages of 45 and 65.^1-4 Many presentations are spontaneous and self-limiting; often all that is required is proper first aid. It is important, however, to recognize the signs and symptoms that are suggestive of more worrisome conditions.

Management of epistaxis requires good preparation, appropriate equipment, and adequate assistance. If any of these are lacking, prompt nasal packing followed by referral to an emergency department or ear, nose, and throat (ENT) service is recommended.

Anatomy of the nasal cavity

The nasal cavity has a rich and highly varied blood supply arising from the internal and external carotid arteries with multiple anastomoses and a crossover between the left and right arterial systems.^2,4,5 The internal maxillary artery (IMAX) supplies 80% of the nasal vault.² The sphenopalatine artery (SPA) supplies most of the nasal septum and the turbinates, while the greater palatine artery (GPA) supplies the floor of the nasal septum.^3,5 The ethmoidal arteries course through the cribriform plate to supply the roof of the nasal cavity. The ethmoidal arteries communicates with branches of the SPA posteriorly and several branches anteriorly (FIGURE 1).

Kiesselbach’s plexus is a highly vascularized region of cartilaginous nasal septum anteroinferiorly that is also known as Little’s area. It is supplied by the SPA, GPA, superior labial artery, and ethmoidal arteries.⁵ Woodruff’s plexus is the richly vascularized posterior aspect of the nasal cavity primarily supplied by the SPA.^3,5

Is the bleed anterior or posterior; primary or secondary?

Epistaxis is classified as anterior or posterior based on the arterial supply and the location of the bleed in relation to the piriform aperture.^2,3 Anterior epistaxis occurs in >90% of patients and arises in Little’s area.⁶ Posterior epistaxis arises from Woodruff’s plexus in the posterior nasal septum or lateral nasal wall. It occurs in 5% to 10% of patients, is usually arterial in origin, and leads to a greater risk of airway compromise, aspiration, and difficulty in controlling the hemorrhage.^2,6

Epistaxis can be classified further as primary or secondary hemorrhage. Primary epistaxis is idiopathic, spontaneous bleeds without any precipitants.² Blood vessels within the nasal mucosa run superficially and are relatively unprotected. Damage to this mucosa and to vessel walls can result in bleeding.⁴ Spontaneous rupture of vessels may occur occasionally, during, say the Valsalva maneuver or when straining to lift heavy objects.⁴ Secondary epistaxis occurs when there is a clear and definite cause (eg trauma, anticoagulant use, or surgery).

Continue to: Numerous causes...

Epistaxis can be caused by local, systemic, or environmental factors; medications; or be idiopathic in nature (TABLE 1²). It commonly arises due to self-inflicted trauma from nose picking, particularly in children; trauma to nasal bones or septum; and mucosal irritation from topical nasal drugs, such as corticosteroids and antihistamines. Other local factors include septal abnormalities, such as septal perforation, inflammatory diseases, rhinosinusitis, illicit drug use (eg cocaine), iatrogenic causes, and neoplasia.

Red flags for neoplasia include unilateral or asymmetric symptoms, such as nasal blockage, facial pain, rhinorrhea, headaches, facial swelling or deformity, and cranial neuropathies (ie, facial numbness or double vision). Other red flags include Southeast Asian origin (nasopharyngeal carcinoma), loose maxillary teeth, and deep otalgia (TABLE 2²). In adolescent males, it is important to consider juvenile nasopharyngeal angiofibroma, a benign tumor that can bleed extensively.

Systemic factors include age, hypertension, alcohol use, acquired coagulopathies due to liver or renal disease, hematologic abnormalities, circadian rhythms, and genetic disorders such as hereditary hemorrhagic telangiectasia (HHT), hemophilia, and von Willebrand’s disease.²

Medications that contribute to epistaxis include antiplatelet agents, such as aspirin and clopidogrel; nonsteroidal anti-inflammatory drugs (NSAIDs); warfarin and novel oral anticoagulants (NOACs); and complementary and alternative medicines, such garlic, gingko, and ginseng. Environmental factors include temperature and humidity.²

Ask about trauma, but also about upper GI hemorrhage

Resuscitation and control of bleeding (which we’ll discuss in a moment) should always take priority. A thorough history and examination are also essential. It’s important to elicit details of the acute episode and any previous episodes, including the duration, severity, frequency, laterality of bleed, and contributing or inciting factors.^1,2 Posterior epistaxis often occurs from both nostrils and feels as though blood is dripping down the throat rather than the nose.

Continue to: Hematemesis and melena from upper gastrointestinal hemorrhage...

Hematemesis and melena from upper gastrointestinal hemorrhage can often be overlooked. Elicit history of local trauma, including nose picking, possible foreign body (particularly batteries in children), and recurrent upper respiratory tract infections.

Treatments, including methods previously used to control episodes, can be instructive. Pinching over the nasal bones—rather than the soft cartilaginous part of the nose—unfortunately remains relatively common. Ask about any past medical history that can give clues to the cause of bleeding, such as hypertension, hepatic impairment, easy bruising, family history of coagulation disorders, and social history including alcohol intake, smoking, and recreational drug use—particularly cocaine use. A detailed medication history, as discussed earlier, is vital.

Initial management: Digital pressure

Epistaxis is potentially a life-threatening event. All patients who are actively bleeding require full assessment, resuscitation, and control of the bleeding.⁴ To protect the airway sit the patient upright and lean them forward to prevent aspiration of blood posteriorly into the pharynx. To control bleeding, get the patient to apply digital pressure at the cartilaginous part of the nose for a minimum of 10 minutes. This provides tamponade of the anterior septal vessels. Applying ice packs around the neck and having the patient suck on ice significantly reduces nasal mucosa blood flow and can slow down the bleeding.⁷

If there is significant bleeding

Monitor the patient’s vital signs, in particular, the pulse and respiratory rate. Assess the patient’s hemodynamic stability and look for signs of shock, such as sweating and pallor. Insert 2 large-bore (16 G) intravenous cannula and draw blood for type and crossmatch for potential transfusion if significant bleeding has occurred, in high risk patients (eg patients who are elderly or anticoagulated or have a suspected bleeding diathesis), or if further bleeding is likely to occur.²

Consider fluid resuscitation with intravenous saline initially and blood transfusions based on hemoglobin level, symptoms, and history of ischemic heart disease.^3,6 Routine clotting studies need to be performed if there is a suspected bleeding diathesis or the patient is anticoagulated. Test for hepatic or renal dysfunction in patients with systemic conditions that could lead to coagulopathy. The clinical state of an elderly patient may deteriorate rapidly, so aggressive resuscitation is vital.⁴

Continue to: Getting a better look requires the proper equipment

Universal precautions including facemask, eye protection, and gloves should be worn. Have equipment easily accessible, including sufficient lighting and suction. A headlight enables the use of both hands to assess and treat the patient. The nasal cavity often is obscured by clots, so ask the patient to blow and clear their nose. Although this may lead to a recurrence of bleeding, it could assist in identifying the bleeding point.²

Local anesthetic with a vasoconstrictor should be applied to the nasal mucosa over Little’s area either via a solution applied on cotton-tipped applicator or as a nasal spray. Once adequate local anesthesia is achieved, the nasal cavity can be examined and treatment instigated to stem the hemorrhage. Perform anterior rhinoscopy with a Thudicum’s speculum with one hand (FIGURE 2) while suctioning simultaneously with the other. Assess the nasal cavity systematically, paying particular attention to the septum and Little’s area for an anterior bleed. Look for scabbed and excoriated areas.

Anterior bleeds can be managed safely in primary care, provided that appropriate equipment is available. Consider transfer to an emergency department or referral to an ENT specialist if bleeding continues or if a posterior bleed is suspected.² Examination of the entire nasal cavity via nasendoscopy may be required to identify the source of bleeding—especially with posterior bleeds.

Nonsurgical management

Topical agents

Topical vasoconstrictor and local anaesthetic agents are widely available, and their limited adverse effect profiles make them a convenient first-line therapy.^6,8 These agents reduce hemorrhage to allow for better visualization and analgesia for possible cautery or nasal packing.² Common preparations include cophenylcaine (topical 5% lidocaine solution with 0.5% phenylephrine) and lidocaine injection (0.5%, 1%, or 2%) with epinephrine 1 in 200,000 and cocaine topical solutions (2% or 5%). Topical tranexamic acid has shown significant benefits in acute epistaxis in a systematic review.⁹

Cautery

If direct pressure and medical therapy fail to stop the bleeding, cautery or nasal packing can be performed.^2,8 Chemical cautery entails application of 75% silver nitrate sticks to the bleeding point with firm pressure for 5 to 10 seconds to produce a local chemical burn.⁴ Only one side of the septum should be cauterized, as there is a small risk of septal perforation resulting from decreased vascularization to the septal cartilage.^2,4,8 This can be performed at 4 to 6 week intervals. Electric bipolar cautery with a metal loop is performed by otolaryngologists under local anesthesia.⁴ Compared with electric cautery, silver nitrate cautery is cheap, readily available, easy to perform, equal in effectiveness, and has fewer complications.¹⁰

Continue to: Nasal packing...

Nasal packing

Nasal packing can be performed if cautery is unsuccessful in controlling the bleed or if no bleeding point is seen on examination.² It provides direct mechanical compression and acts as a platelet aggregator, thereby facilitating coagulation.

Anterior packing. Packs should be directed posteriorly along the floor of the nasal cavity, rather than superiorly.² After packing, examine the patient for ongoing bleeding from the contralateral nares or posteriorly in the oropharynx using a tongue depressor. If bleeding is seen, consider packing the other side before removal of the already inserted pack to increase the tamponade pressure over the septum.⁴

Anterior packs are effective, easy to use, widely available, and inexpensive.⁸ Types of packs include traditional packing, nasal tampons, and absorbable packing materials.

The Rapid Rhino is also an option. It’s an inflatable balloon pack coated with a lubricating compound. It remains in contact with the mucosa when deflated and can be left in situ for up to 4 days (FIGURE 3). It has the same rate of control of epistaxis when compared with polyvinyl alcohol. Both patients and physicians found insertion and removal of the Rapid Rhino easier with less patient discomfort.^11-13

Absorbable packs do not require formal removal and are useful for patients with or without coagulopathies. They can be applied topically with a syringe that conforms to the 3-dimensional structure of the nasal cavity.¹ The decision regarding which product to use is based on availability, cost, and physician preference.

Continue to: Posterior packing...

Posterior packing may be required if epistaxis continues despite anterior packing and may take the form of a balloon or a formal pack. A Foley catheter inflated with 3 to 4 mL of water or air is inserted through the anterior nares, along the floor of the nasal cavity into the posterior pharynx and pulled forward until the balloon engages the posterior choana (FIGURE 4). This provides local tamponade and tamponade at the sphenopalatine foramen.^2,4 The balloon is held firmly in place with an umbilical clamp at the anterior nares. To prevent pressure necrosis, the columella can be protected with a soft dressing that is regularly checked by the nursing staff. The nasal cavity is then packed anteriorly with ribbon gauze or a nasal sponge to stem any potential anterior bleeds.

Potential complications include posterior displacement of the balloon with potential airway compromise, deflation in situ, and rupture of the balloon—which could result in aspiration.⁴ It is important to note the Foley catheter is, in fact, not licensed for nasal use.⁴ Insertion only should be performed by a clinician who has been trained in this skill.

Traditional nasopharyngeal packs are rolled gauze attached to tapes or sutured to a catheter. Compared with balloons, they were found to be more effective in controlling epistaxis and produce less short- and long-term complications.² However, they are rather uncomfortable and hence normally performed under general anesthesia.⁴ Posterior packing has many disadvantages. They have a 50% failure rate, which increases to 70% in patients with bleeding disorders.⁸

Complications vary from mild and self-limiting such as infection, hemorrhage, and pressure effects to severe such as toxic shock syndrome, myocardial infarction, and death (TABLE 3^2-4,6,8). There is little evidence supporting the use of prophylactic oral antibiotics after packing. Prophylactic antibiotics are reserved for those with posterior packs or if packs remain in situ for more than 24 hours.⁶

Warm water irrigation

Warm water irrigation via Foley catheter has a reported 82% success rate.⁸ It results in earlier discharge, less pain, less trauma to the nose, and reduced hospital length of stay.¹³ The balloon catheter is used to close off the posterior choana and water irrigation is applied at 45° C to 50° C for about 3 minutes with the help of a caloric stimulator.^4,8 It helps clear blood clots from the nose and reduces local blood flow by causing mucosal edema, which compresses the bleeding vessels.

Continue to: Surgical management

Any bleeding that fails to stop, despite an escalation of management, requires surgical intervention. This includes cases in which the bleeding continues after pack removal.⁴ Options include⁴:

• Diathermy, with bipolar or radiofrequency laser, can be used to localize the bleeding site.
• Septoplasty allows for better access to the nasal cavity, reduction of blood flow to the nasal mucosa by raising a mucoperichondrial flap, correction of a deviated septum, and removal of a septal spur that may be responsible for the epistaxis.
• Arterial ligation involves identification of the bleeding vessel that is clipped or coagulated with bipolar diathermy.
• Endoscopic SPA ligation is an excellent, well-tolerated, and cost-effective method of treating recurrent epistaxis.^6,14 It controls 98% of posterior epistaxis, and is superior to posterior nasal packing and embolization.^2,3,10 It results in a shorter hospital stay, reduction in repeated hemorrhage and painful packing procedures, and a cost saving of >$7,000 per patient if performed early.⁷ Concomitant ligation of the anterior ethmoidal artery may be performed in traumatic epistaxis or when severe bleeding is from the ethmoidal region.^4,6
• Ligation of the IMAX and external carotid arteries is performed rarely due to potential complications and high failure rates.

Arterial embolization

When arterial ligation fails, or is not possible due to anesthetic concerns, selective embolization of the maxillary or facial arteries by specialist radiologists can be considered.⁶ Access to the vascular system through a femoral punch leads to identification of the bleeding point. A catheter is then placed in the artery and the bleeding vessel is embolized. Possible candidates include patients with HHT, bleeding tumors, poor surgical candidates, or patient preference.³

Other management considerations

Once bleeding is controlled, factors that contributed to the epistaxis should be addressed.³ Hypertension needs to be managed. Antiplatelet or anticoagulant therapy may need to be temporarily halted in consultation with specialist physicians. Local treatments such as cautery are unlikely to be effective in patients who are anticoagulated. Nasal packing with a ‘procoagulant’ dressing, such as Kaltostat or Rapid Rhino, is often required.

Patient education and follow-up

Patients should be started on saline sprays or irrigation to maintain nasal hygiene after acute epistaxis. It’s a good idea to teach patients about proper first aid for recurrence (eg, sitting upright with digital pressure applied to the cartilaginous part of the nose, ice packs around the neck and ice to suck) and to encourage them to refrain from activities that may stimulate bleeding (blowing or picking the nose, heavy lifting, strenuous exercise). Also advise patients to abstain from alcohol and hot drinks that cause vasodilatation of nasal vessels as much as possible.⁴ Advise patients that topical gels, lotions, and ointments such as kenacomb, nasalate, or paraffin can be used to moisturise the mucosa and promote healing.¹

All patients with a history of severe or recurrent epistaxis require formal examination of the nasal cavity to rule out a neoplastic lesion.

CORRESPONDENCE
Amy Wong, BMBS, Department ENT/Head and Neck Surgery, Monash ENT Building, PO Box 72, Rear 867 Centre Road, Bentleigh East 3165 Australia, [email protected].

Epistaxis is a common presenting complaint in family medicine. Successful treatment requires knowledge of nasal anatomy, possible causes, and a step-wise approach.

Epistaxis predominantly affects children between the ages of 2 and 10 years and older adults between the ages of 45 and 65.^1-4 Many presentations are spontaneous and self-limiting; often all that is required is proper first aid. It is important, however, to recognize the signs and symptoms that are suggestive of more worrisome conditions.

Management of epistaxis requires good preparation, appropriate equipment, and adequate assistance. If any of these are lacking, prompt nasal packing followed by referral to an emergency department or ear, nose, and throat (ENT) service is recommended.

Anatomy of the nasal cavity

The nasal cavity has a rich and highly varied blood supply arising from the internal and external carotid arteries with multiple anastomoses and a crossover between the left and right arterial systems.^2,4,5 The internal maxillary artery (IMAX) supplies 80% of the nasal vault.² The sphenopalatine artery (SPA) supplies most of the nasal septum and the turbinates, while the greater palatine artery (GPA) supplies the floor of the nasal septum.^3,5 The ethmoidal arteries course through the cribriform plate to supply the roof of the nasal cavity. The ethmoidal arteries communicates with branches of the SPA posteriorly and several branches anteriorly (FIGURE 1).

Kiesselbach’s plexus is a highly vascularized region of cartilaginous nasal septum anteroinferiorly that is also known as Little’s area. It is supplied by the SPA, GPA, superior labial artery, and ethmoidal arteries.⁵ Woodruff’s plexus is the richly vascularized posterior aspect of the nasal cavity primarily supplied by the SPA.^3,5

Is the bleed anterior or posterior; primary or secondary?

Epistaxis is classified as anterior or posterior based on the arterial supply and the location of the bleed in relation to the piriform aperture.^2,3 Anterior epistaxis occurs in >90% of patients and arises in Little’s area.⁶ Posterior epistaxis arises from Woodruff’s plexus in the posterior nasal septum or lateral nasal wall. It occurs in 5% to 10% of patients, is usually arterial in origin, and leads to a greater risk of airway compromise, aspiration, and difficulty in controlling the hemorrhage.^2,6

Epistaxis can be classified further as primary or secondary hemorrhage. Primary epistaxis is idiopathic, spontaneous bleeds without any precipitants.² Blood vessels within the nasal mucosa run superficially and are relatively unprotected. Damage to this mucosa and to vessel walls can result in bleeding.⁴ Spontaneous rupture of vessels may occur occasionally, during, say the Valsalva maneuver or when straining to lift heavy objects.⁴ Secondary epistaxis occurs when there is a clear and definite cause (eg trauma, anticoagulant use, or surgery).

Continue to: Numerous causes...

Epistaxis can be caused by local, systemic, or environmental factors; medications; or be idiopathic in nature (TABLE 1²). It commonly arises due to self-inflicted trauma from nose picking, particularly in children; trauma to nasal bones or septum; and mucosal irritation from topical nasal drugs, such as corticosteroids and antihistamines. Other local factors include septal abnormalities, such as septal perforation, inflammatory diseases, rhinosinusitis, illicit drug use (eg cocaine), iatrogenic causes, and neoplasia.

Red flags for neoplasia include unilateral or asymmetric symptoms, such as nasal blockage, facial pain, rhinorrhea, headaches, facial swelling or deformity, and cranial neuropathies (ie, facial numbness or double vision). Other red flags include Southeast Asian origin (nasopharyngeal carcinoma), loose maxillary teeth, and deep otalgia (TABLE 2²). In adolescent males, it is important to consider juvenile nasopharyngeal angiofibroma, a benign tumor that can bleed extensively.

Systemic factors include age, hypertension, alcohol use, acquired coagulopathies due to liver or renal disease, hematologic abnormalities, circadian rhythms, and genetic disorders such as hereditary hemorrhagic telangiectasia (HHT), hemophilia, and von Willebrand’s disease.²

Medications that contribute to epistaxis include antiplatelet agents, such as aspirin and clopidogrel; nonsteroidal anti-inflammatory drugs (NSAIDs); warfarin and novel oral anticoagulants (NOACs); and complementary and alternative medicines, such garlic, gingko, and ginseng. Environmental factors include temperature and humidity.²

Ask about trauma, but also about upper GI hemorrhage

Resuscitation and control of bleeding (which we’ll discuss in a moment) should always take priority. A thorough history and examination are also essential. It’s important to elicit details of the acute episode and any previous episodes, including the duration, severity, frequency, laterality of bleed, and contributing or inciting factors.^1,2 Posterior epistaxis often occurs from both nostrils and feels as though blood is dripping down the throat rather than the nose.

Continue to: Hematemesis and melena from upper gastrointestinal hemorrhage...

Hematemesis and melena from upper gastrointestinal hemorrhage can often be overlooked. Elicit history of local trauma, including nose picking, possible foreign body (particularly batteries in children), and recurrent upper respiratory tract infections.

Treatments, including methods previously used to control episodes, can be instructive. Pinching over the nasal bones—rather than the soft cartilaginous part of the nose—unfortunately remains relatively common. Ask about any past medical history that can give clues to the cause of bleeding, such as hypertension, hepatic impairment, easy bruising, family history of coagulation disorders, and social history including alcohol intake, smoking, and recreational drug use—particularly cocaine use. A detailed medication history, as discussed earlier, is vital.

Initial management: Digital pressure

Epistaxis is potentially a life-threatening event. All patients who are actively bleeding require full assessment, resuscitation, and control of the bleeding.⁴ To protect the airway sit the patient upright and lean them forward to prevent aspiration of blood posteriorly into the pharynx. To control bleeding, get the patient to apply digital pressure at the cartilaginous part of the nose for a minimum of 10 minutes. This provides tamponade of the anterior septal vessels. Applying ice packs around the neck and having the patient suck on ice significantly reduces nasal mucosa blood flow and can slow down the bleeding.⁷

If there is significant bleeding

Monitor the patient’s vital signs, in particular, the pulse and respiratory rate. Assess the patient’s hemodynamic stability and look for signs of shock, such as sweating and pallor. Insert 2 large-bore (16 G) intravenous cannula and draw blood for type and crossmatch for potential transfusion if significant bleeding has occurred, in high risk patients (eg patients who are elderly or anticoagulated or have a suspected bleeding diathesis), or if further bleeding is likely to occur.²

Consider fluid resuscitation with intravenous saline initially and blood transfusions based on hemoglobin level, symptoms, and history of ischemic heart disease.^3,6 Routine clotting studies need to be performed if there is a suspected bleeding diathesis or the patient is anticoagulated. Test for hepatic or renal dysfunction in patients with systemic conditions that could lead to coagulopathy. The clinical state of an elderly patient may deteriorate rapidly, so aggressive resuscitation is vital.⁴

Continue to: Getting a better look requires the proper equipment

Universal precautions including facemask, eye protection, and gloves should be worn. Have equipment easily accessible, including sufficient lighting and suction. A headlight enables the use of both hands to assess and treat the patient. The nasal cavity often is obscured by clots, so ask the patient to blow and clear their nose. Although this may lead to a recurrence of bleeding, it could assist in identifying the bleeding point.²

Local anesthetic with a vasoconstrictor should be applied to the nasal mucosa over Little’s area either via a solution applied on cotton-tipped applicator or as a nasal spray. Once adequate local anesthesia is achieved, the nasal cavity can be examined and treatment instigated to stem the hemorrhage. Perform anterior rhinoscopy with a Thudicum’s speculum with one hand (FIGURE 2) while suctioning simultaneously with the other. Assess the nasal cavity systematically, paying particular attention to the septum and Little’s area for an anterior bleed. Look for scabbed and excoriated areas.

Anterior bleeds can be managed safely in primary care, provided that appropriate equipment is available. Consider transfer to an emergency department or referral to an ENT specialist if bleeding continues or if a posterior bleed is suspected.² Examination of the entire nasal cavity via nasendoscopy may be required to identify the source of bleeding—especially with posterior bleeds.

Nonsurgical management

Topical agents

Topical vasoconstrictor and local anaesthetic agents are widely available, and their limited adverse effect profiles make them a convenient first-line therapy.^6,8 These agents reduce hemorrhage to allow for better visualization and analgesia for possible cautery or nasal packing.² Common preparations include cophenylcaine (topical 5% lidocaine solution with 0.5% phenylephrine) and lidocaine injection (0.5%, 1%, or 2%) with epinephrine 1 in 200,000 and cocaine topical solutions (2% or 5%). Topical tranexamic acid has shown significant benefits in acute epistaxis in a systematic review.⁹

Cautery

If direct pressure and medical therapy fail to stop the bleeding, cautery or nasal packing can be performed.^2,8 Chemical cautery entails application of 75% silver nitrate sticks to the bleeding point with firm pressure for 5 to 10 seconds to produce a local chemical burn.⁴ Only one side of the septum should be cauterized, as there is a small risk of septal perforation resulting from decreased vascularization to the septal cartilage.^2,4,8 This can be performed at 4 to 6 week intervals. Electric bipolar cautery with a metal loop is performed by otolaryngologists under local anesthesia.⁴ Compared with electric cautery, silver nitrate cautery is cheap, readily available, easy to perform, equal in effectiveness, and has fewer complications.¹⁰

Continue to: Nasal packing...

Nasal packing

Nasal packing can be performed if cautery is unsuccessful in controlling the bleed or if no bleeding point is seen on examination.² It provides direct mechanical compression and acts as a platelet aggregator, thereby facilitating coagulation.

Anterior packing. Packs should be directed posteriorly along the floor of the nasal cavity, rather than superiorly.² After packing, examine the patient for ongoing bleeding from the contralateral nares or posteriorly in the oropharynx using a tongue depressor. If bleeding is seen, consider packing the other side before removal of the already inserted pack to increase the tamponade pressure over the septum.⁴

Anterior packs are effective, easy to use, widely available, and inexpensive.⁸ Types of packs include traditional packing, nasal tampons, and absorbable packing materials.

The Rapid Rhino is also an option. It’s an inflatable balloon pack coated with a lubricating compound. It remains in contact with the mucosa when deflated and can be left in situ for up to 4 days (FIGURE 3). It has the same rate of control of epistaxis when compared with polyvinyl alcohol. Both patients and physicians found insertion and removal of the Rapid Rhino easier with less patient discomfort.^11-13

Absorbable packs do not require formal removal and are useful for patients with or without coagulopathies. They can be applied topically with a syringe that conforms to the 3-dimensional structure of the nasal cavity.¹ The decision regarding which product to use is based on availability, cost, and physician preference.

Continue to: Posterior packing...

Posterior packing may be required if epistaxis continues despite anterior packing and may take the form of a balloon or a formal pack. A Foley catheter inflated with 3 to 4 mL of water or air is inserted through the anterior nares, along the floor of the nasal cavity into the posterior pharynx and pulled forward until the balloon engages the posterior choana (FIGURE 4). This provides local tamponade and tamponade at the sphenopalatine foramen.^2,4 The balloon is held firmly in place with an umbilical clamp at the anterior nares. To prevent pressure necrosis, the columella can be protected with a soft dressing that is regularly checked by the nursing staff. The nasal cavity is then packed anteriorly with ribbon gauze or a nasal sponge to stem any potential anterior bleeds.

Potential complications include posterior displacement of the balloon with potential airway compromise, deflation in situ, and rupture of the balloon—which could result in aspiration.⁴ It is important to note the Foley catheter is, in fact, not licensed for nasal use.⁴ Insertion only should be performed by a clinician who has been trained in this skill.

Traditional nasopharyngeal packs are rolled gauze attached to tapes or sutured to a catheter. Compared with balloons, they were found to be more effective in controlling epistaxis and produce less short- and long-term complications.² However, they are rather uncomfortable and hence normally performed under general anesthesia.⁴ Posterior packing has many disadvantages. They have a 50% failure rate, which increases to 70% in patients with bleeding disorders.⁸

Complications vary from mild and self-limiting such as infection, hemorrhage, and pressure effects to severe such as toxic shock syndrome, myocardial infarction, and death (TABLE 3^2-4,6,8). There is little evidence supporting the use of prophylactic oral antibiotics after packing. Prophylactic antibiotics are reserved for those with posterior packs or if packs remain in situ for more than 24 hours.⁶

Warm water irrigation

Warm water irrigation via Foley catheter has a reported 82% success rate.⁸ It results in earlier discharge, less pain, less trauma to the nose, and reduced hospital length of stay.¹³ The balloon catheter is used to close off the posterior choana and water irrigation is applied at 45° C to 50° C for about 3 minutes with the help of a caloric stimulator.^4,8 It helps clear blood clots from the nose and reduces local blood flow by causing mucosal edema, which compresses the bleeding vessels.

Continue to: Surgical management

Any bleeding that fails to stop, despite an escalation of management, requires surgical intervention. This includes cases in which the bleeding continues after pack removal.⁴ Options include⁴:

• Diathermy, with bipolar or radiofrequency laser, can be used to localize the bleeding site.
• Septoplasty allows for better access to the nasal cavity, reduction of blood flow to the nasal mucosa by raising a mucoperichondrial flap, correction of a deviated septum, and removal of a septal spur that may be responsible for the epistaxis.
• Arterial ligation involves identification of the bleeding vessel that is clipped or coagulated with bipolar diathermy.
• Endoscopic SPA ligation is an excellent, well-tolerated, and cost-effective method of treating recurrent epistaxis.^6,14 It controls 98% of posterior epistaxis, and is superior to posterior nasal packing and embolization.^2,3,10 It results in a shorter hospital stay, reduction in repeated hemorrhage and painful packing procedures, and a cost saving of >$7,000 per patient if performed early.⁷ Concomitant ligation of the anterior ethmoidal artery may be performed in traumatic epistaxis or when severe bleeding is from the ethmoidal region.^4,6
• Ligation of the IMAX and external carotid arteries is performed rarely due to potential complications and high failure rates.

Arterial embolization

When arterial ligation fails, or is not possible due to anesthetic concerns, selective embolization of the maxillary or facial arteries by specialist radiologists can be considered.⁶ Access to the vascular system through a femoral punch leads to identification of the bleeding point. A catheter is then placed in the artery and the bleeding vessel is embolized. Possible candidates include patients with HHT, bleeding tumors, poor surgical candidates, or patient preference.³

Other management considerations

Once bleeding is controlled, factors that contributed to the epistaxis should be addressed.³ Hypertension needs to be managed. Antiplatelet or anticoagulant therapy may need to be temporarily halted in consultation with specialist physicians. Local treatments such as cautery are unlikely to be effective in patients who are anticoagulated. Nasal packing with a ‘procoagulant’ dressing, such as Kaltostat or Rapid Rhino, is often required.

Patient education and follow-up

Patients should be started on saline sprays or irrigation to maintain nasal hygiene after acute epistaxis. It’s a good idea to teach patients about proper first aid for recurrence (eg, sitting upright with digital pressure applied to the cartilaginous part of the nose, ice packs around the neck and ice to suck) and to encourage them to refrain from activities that may stimulate bleeding (blowing or picking the nose, heavy lifting, strenuous exercise). Also advise patients to abstain from alcohol and hot drinks that cause vasodilatation of nasal vessels as much as possible.⁴ Advise patients that topical gels, lotions, and ointments such as kenacomb, nasalate, or paraffin can be used to moisturise the mucosa and promote healing.¹

All patients with a history of severe or recurrent epistaxis require formal examination of the nasal cavity to rule out a neoplastic lesion.

CORRESPONDENCE
Amy Wong, BMBS, Department ENT/Head and Neck Surgery, Monash ENT Building, PO Box 72, Rear 867 Centre Road, Bentleigh East 3165 Australia, [email protected].

A relatively recent practice catching on in many different hospitalist groups is geographic cohorting, or unit-based assignments. Traditionally, most hospitalists have had patients assigned on multiple different units. Unit-based assignments have been touted as a way of improving interdisciplinary communication and provider and patient satisfaction.¹

How frequently are hospital medicine groups using unit-based assignments? SHM sought to quantify this trend in the recently published 2018 State of Hospital Medicine Report. Overall, among hospital medicine groups serving adults only, a little over one-third (36.4%) of groups reported utilizing unit-based assignments. However, there was significant variation, particularly dependent on group size. Geographic cohorting was used only in 7.6% of groups with 4 or fewer full-time equivalents, and in 68.8% of groups with 30 or more FTE. These data seem logical, as the potential gains from cohorting likely increase with group/hospital size, where physicians would otherwise round on an increasingly large number of units.

As has been shared in the hospital medicine literature, groups have experienced variable success with geographic cohorting. Improvements have been achieved in interprofessional collaboration, efficiency, nursing satisfaction,² and, in some instances, length of stay. Unit-based assignments have allowed some groups to pilot other interventions, such as interdisciplinary rounds.

But geographic cohorting comes with its implementation challenges, too. For example, in many hospitals, some units have differing telemetry or nursing capabilities. And, in other institutions, there are units providing specialized care, such as care for neurology or oncology patients. The workload for hospitalists caring for particular types of patients may vary, and with specialty units, it may be more difficult to keep a similar census assigned to each hospitalist.

While some groups have noted increased professional satisfaction, others have noted decreases in satisfaction. One reason is that, while the frequency of paging may decrease, this is replaced by an increase in face-to-face interruptions. Also, unit-based assignments in some groups have resulted in hospitalists perceiving they are working in silos because of a decrease in interactions and camaraderie among providers in the same hospital medicine group.

At my home institution, University of California, San Diego, geographic cohorting has largely been a successful and positively perceived change. Our efforts have been particularly successful at one of our two campuses where most units have telemetry capabilities and where we have a dedicated daytime admitter (there are data on this in the Report as well, and a dedicated daytime admitter is the topic of a future Survey Insights column). Unit-based assignments have allowed the implementation of what we’ve termed focused interdisciplinary rounds.

Our unit-based assignments are not perfect – we re-cohort each week when new hospitalists come on service, and some hospitalists are assigned a small number of patients off their home unit. Our internal data have shown a significant increase in patient satisfaction scores, but we have not realized a decrease in length of stay. Despite an overall positive perception, hospitalists have sometimes noted an imbalanced workload – we have a particularly challenging oncology/palliative unit and a daytime admitter that is at times very busy. Our system also requires the use of physician time to assign patients each morning and each week.

In contrast, while we’ve aimed to achieve the same success with unit-based assignments at our other campus, we’ve faced more challenges there. Our other facility is older, and fewer units have telemetry capabilities. A more traditional teaching structure also means that teams take turns with on-call admitting days, as opposed to a daytime admitter structure, and there may not be beds available in the unit assigned to the admitting team of the day.

Overall, geographic cohorting is likely to be considered or implemented in many hospital medicine groups, and efforts have met with varying success. There are certainly pros and cons to every model, and if your group is looking at redesigning services to include unit-based assignments, it’s worth examining the intended outcomes. While unit-based assignments are not for every group, there’s no doubt that this trend has been driven by our specialty’s commitment to outcome-driven process improvement.

Addendum added Feb. 15, 2019: The impact of UC San Diego's efforts discussed in this article are the author's own opinions through limited participation in focused interdisciplinary rounds, and have not been validated with formal data analysis. More study is in progress on the impact of focused interdiscplinary rounds on communication, utilization, and quality metrics. Sarah Horman, MD ([email protected]), Daniel Bouland, MD ([email protected]), and William Frederick, MD ([email protected]), have led efforts at UC San Diego to develop and implement focused interdisciplinary rounds, and may be contacted for further information.

Dr. Huang is physician advisor for care management and associate clinical professor in the division of hospital medicine at the University of California, San Diego. He is a member of SHM’s practice analysis subcommittee.

References

1. O’Leary KJ et al. Interdisciplinary teamwork in hospitals: A review and practical recommendations for improvement. J Hosp Med. 2012 Jan;7(1):48-54.

2. Kara A et al. Hospital-based clinicians’ perceptions of geographic cohorting: Identifying opportunities for improvement. Am J Med Qual. 2018 May/Jun;33(3):303-12.

A relatively recent practice catching on in many different hospitalist groups is geographic cohorting, or unit-based assignments. Traditionally, most hospitalists have had patients assigned on multiple different units. Unit-based assignments have been touted as a way of improving interdisciplinary communication and provider and patient satisfaction.¹

How frequently are hospital medicine groups using unit-based assignments? SHM sought to quantify this trend in the recently published 2018 State of Hospital Medicine Report. Overall, among hospital medicine groups serving adults only, a little over one-third (36.4%) of groups reported utilizing unit-based assignments. However, there was significant variation, particularly dependent on group size. Geographic cohorting was used only in 7.6% of groups with 4 or fewer full-time equivalents, and in 68.8% of groups with 30 or more FTE. These data seem logical, as the potential gains from cohorting likely increase with group/hospital size, where physicians would otherwise round on an increasingly large number of units.

As has been shared in the hospital medicine literature, groups have experienced variable success with geographic cohorting. Improvements have been achieved in interprofessional collaboration, efficiency, nursing satisfaction,² and, in some instances, length of stay. Unit-based assignments have allowed some groups to pilot other interventions, such as interdisciplinary rounds.

But geographic cohorting comes with its implementation challenges, too. For example, in many hospitals, some units have differing telemetry or nursing capabilities. And, in other institutions, there are units providing specialized care, such as care for neurology or oncology patients. The workload for hospitalists caring for particular types of patients may vary, and with specialty units, it may be more difficult to keep a similar census assigned to each hospitalist.

While some groups have noted increased professional satisfaction, others have noted decreases in satisfaction. One reason is that, while the frequency of paging may decrease, this is replaced by an increase in face-to-face interruptions. Also, unit-based assignments in some groups have resulted in hospitalists perceiving they are working in silos because of a decrease in interactions and camaraderie among providers in the same hospital medicine group.

At my home institution, University of California, San Diego, geographic cohorting has largely been a successful and positively perceived change. Our efforts have been particularly successful at one of our two campuses where most units have telemetry capabilities and where we have a dedicated daytime admitter (there are data on this in the Report as well, and a dedicated daytime admitter is the topic of a future Survey Insights column). Unit-based assignments have allowed the implementation of what we’ve termed focused interdisciplinary rounds.

Our unit-based assignments are not perfect – we re-cohort each week when new hospitalists come on service, and some hospitalists are assigned a small number of patients off their home unit. Our internal data have shown a significant increase in patient satisfaction scores, but we have not realized a decrease in length of stay. Despite an overall positive perception, hospitalists have sometimes noted an imbalanced workload – we have a particularly challenging oncology/palliative unit and a daytime admitter that is at times very busy. Our system also requires the use of physician time to assign patients each morning and each week.

In contrast, while we’ve aimed to achieve the same success with unit-based assignments at our other campus, we’ve faced more challenges there. Our other facility is older, and fewer units have telemetry capabilities. A more traditional teaching structure also means that teams take turns with on-call admitting days, as opposed to a daytime admitter structure, and there may not be beds available in the unit assigned to the admitting team of the day.

Overall, geographic cohorting is likely to be considered or implemented in many hospital medicine groups, and efforts have met with varying success. There are certainly pros and cons to every model, and if your group is looking at redesigning services to include unit-based assignments, it’s worth examining the intended outcomes. While unit-based assignments are not for every group, there’s no doubt that this trend has been driven by our specialty’s commitment to outcome-driven process improvement.

Addendum added Feb. 15, 2019: The impact of UC San Diego's efforts discussed in this article are the author's own opinions through limited participation in focused interdisciplinary rounds, and have not been validated with formal data analysis. More study is in progress on the impact of focused interdiscplinary rounds on communication, utilization, and quality metrics. Sarah Horman, MD ([email protected]), Daniel Bouland, MD ([email protected]), and William Frederick, MD ([email protected]), have led efforts at UC San Diego to develop and implement focused interdisciplinary rounds, and may be contacted for further information.

Dr. Huang is physician advisor for care management and associate clinical professor in the division of hospital medicine at the University of California, San Diego. He is a member of SHM’s practice analysis subcommittee.

References

1. O’Leary KJ et al. Interdisciplinary teamwork in hospitals: A review and practical recommendations for improvement. J Hosp Med. 2012 Jan;7(1):48-54.

2. Kara A et al. Hospital-based clinicians’ perceptions of geographic cohorting: Identifying opportunities for improvement. Am J Med Qual. 2018 May/Jun;33(3):303-12.

A relatively recent practice catching on in many different hospitalist groups is geographic cohorting, or unit-based assignments. Traditionally, most hospitalists have had patients assigned on multiple different units. Unit-based assignments have been touted as a way of improving interdisciplinary communication and provider and patient satisfaction.¹

How frequently are hospital medicine groups using unit-based assignments? SHM sought to quantify this trend in the recently published 2018 State of Hospital Medicine Report. Overall, among hospital medicine groups serving adults only, a little over one-third (36.4%) of groups reported utilizing unit-based assignments. However, there was significant variation, particularly dependent on group size. Geographic cohorting was used only in 7.6% of groups with 4 or fewer full-time equivalents, and in 68.8% of groups with 30 or more FTE. These data seem logical, as the potential gains from cohorting likely increase with group/hospital size, where physicians would otherwise round on an increasingly large number of units.

As has been shared in the hospital medicine literature, groups have experienced variable success with geographic cohorting. Improvements have been achieved in interprofessional collaboration, efficiency, nursing satisfaction,² and, in some instances, length of stay. Unit-based assignments have allowed some groups to pilot other interventions, such as interdisciplinary rounds.

But geographic cohorting comes with its implementation challenges, too. For example, in many hospitals, some units have differing telemetry or nursing capabilities. And, in other institutions, there are units providing specialized care, such as care for neurology or oncology patients. The workload for hospitalists caring for particular types of patients may vary, and with specialty units, it may be more difficult to keep a similar census assigned to each hospitalist.

While some groups have noted increased professional satisfaction, others have noted decreases in satisfaction. One reason is that, while the frequency of paging may decrease, this is replaced by an increase in face-to-face interruptions. Also, unit-based assignments in some groups have resulted in hospitalists perceiving they are working in silos because of a decrease in interactions and camaraderie among providers in the same hospital medicine group.

At my home institution, University of California, San Diego, geographic cohorting has largely been a successful and positively perceived change. Our efforts have been particularly successful at one of our two campuses where most units have telemetry capabilities and where we have a dedicated daytime admitter (there are data on this in the Report as well, and a dedicated daytime admitter is the topic of a future Survey Insights column). Unit-based assignments have allowed the implementation of what we’ve termed focused interdisciplinary rounds.

Our unit-based assignments are not perfect – we re-cohort each week when new hospitalists come on service, and some hospitalists are assigned a small number of patients off their home unit. Our internal data have shown a significant increase in patient satisfaction scores, but we have not realized a decrease in length of stay. Despite an overall positive perception, hospitalists have sometimes noted an imbalanced workload – we have a particularly challenging oncology/palliative unit and a daytime admitter that is at times very busy. Our system also requires the use of physician time to assign patients each morning and each week.

In contrast, while we’ve aimed to achieve the same success with unit-based assignments at our other campus, we’ve faced more challenges there. Our other facility is older, and fewer units have telemetry capabilities. A more traditional teaching structure also means that teams take turns with on-call admitting days, as opposed to a daytime admitter structure, and there may not be beds available in the unit assigned to the admitting team of the day.

Overall, geographic cohorting is likely to be considered or implemented in many hospital medicine groups, and efforts have met with varying success. There are certainly pros and cons to every model, and if your group is looking at redesigning services to include unit-based assignments, it’s worth examining the intended outcomes. While unit-based assignments are not for every group, there’s no doubt that this trend has been driven by our specialty’s commitment to outcome-driven process improvement.

Addendum added Feb. 15, 2019: The impact of UC San Diego's efforts discussed in this article are the author's own opinions through limited participation in focused interdisciplinary rounds, and have not been validated with formal data analysis. More study is in progress on the impact of focused interdiscplinary rounds on communication, utilization, and quality metrics. Sarah Horman, MD ([email protected]), Daniel Bouland, MD ([email protected]), and William Frederick, MD ([email protected]), have led efforts at UC San Diego to develop and implement focused interdisciplinary rounds, and may be contacted for further information.

Dr. Huang is physician advisor for care management and associate clinical professor in the division of hospital medicine at the University of California, San Diego. He is a member of SHM’s practice analysis subcommittee.

References

1. O’Leary KJ et al. Interdisciplinary teamwork in hospitals: A review and practical recommendations for improvement. J Hosp Med. 2012 Jan;7(1):48-54.

2. Kara A et al. Hospital-based clinicians’ perceptions of geographic cohorting: Identifying opportunities for improvement. Am J Med Qual. 2018 May/Jun;33(3):303-12.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

SAN ANTONIO – Patients with HER2-positive early breast cancer with residual invasive disease following neoadjuvant therapy had a 50% reduction in risk for invasive breast cancer recurrence or death when they were treated with the antibody-drug conjugate trastuzumab emtansine (T-DM1; Kadcyla), results of the KATHERINE trial showed.

Among 743 patients randomized to adjuvant therapy with T-DM1, the 3-year invasive disease-free survival (IDFS) rate was 88.3%, compared with 77.0% for patients assigned to adjuvant trastuzumab (Herceptin).

The hazard ratio for IDFS – a composite endpoint of freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause – was 0.50 (P less than .001), reported Charles E. Geyer Jr., MD, from Virginia Commonwealth University, Richmond.

“While additional follow-up will be necessary to evaluate the effect of T-DM1 on overall survival, the compelling and consistent efficacy seen on the IDFS endpoint with the safety profile will likely form the foundation of a new standard of care in the KATHERINE patient population,” he said at the San Antonio Breast Cancer Symposium.

Results from KATHERINE were published online in the New England Journal of Medicine to coincide with its presentation in a briefing and in a general session.

KATHERINE was an open-label, phase 3 trial pitting T-DM1 against trastuzumab as adjuvant therapy in patients with early HER2-positive breast cancer with residual invasive disease in the breast or axilla at surgery following neoadjuvant therapy with a taxane (with or without an anthracycline) and trastuzumab. After stratification for clinical presentation (operable vs. inoperable), hormone receptor status, type of preoperative therapy, and pathological nodal status after neoadjuvant, patients were randomized to 14 cycles of either T-DM1 or trastuzumab.

The primary endpoint, IDFS, was as noted before. The trial was stopped after the results were found to cross the efficacy stopping boundary (HR less than 0.732) at the prespecified interim IDFS analysis in July 2018.

The efficacy of T-DM1 was supported by the finding that distant recurrence as the first invasive-disease event occurred in 10.5% of patients assigned to T-DM1, compared with 15.9% of those assigned to trastuzumab. The benefit of T-DM1 was consistent across all key subgroups, including all of the aforementioned stratification factors plus age, group, and race.

The safety analysis included data on 740 patients treated with T-DM1 and 720 treated with trastuzumab. The most common grade 3 or greater adverse events in the T-DM1 group included decreased platelet count in 5.7% and hypertension in 2.0%. The most common grade 3 or greater events in the trastuzumab group were hypertension in 1.2% and radiation-related skin injury in 1.0%.

Serious adverse events were more common in the T-DM1 arm, occurring in 12.7% of patients, compared with 8.1% in the trastuzumab arm. Adverse events leading to discontinuation of the trial drug occurred in 18.0% versus 2.1%, in the T-DM1 arm versus trastuzumab arm respectively.

Dr. Geyer said that, in general, adverse events in the T-DM1 arm were consistent with those seen in other studies, with manageable toxicities and no new safety signals.

“At the present time, the role of T-DM1 in the adjuvant and neoadjuvant setting is limited,” commented invited discussant Eric P. Winer, MD, from the Dana-Farber Cancer Institute in Boston. “It’s confined to patients who have residual disease after neoadjuvant therapy, but I predict this will change dramatically over time. Given how well tolerated T-DM1 is, how effective it was in this study, the answer that one comes to is why not consider using it more broadly and in an earlier-stage setting?”

Aditya Bardia, MD, from Massachusetts General Hospital in Boston, who was not involved in KATHERINE, agreed that the trial results are practice changing.

“I anticipate we would be using T-DM1 in the future for patients who would otherwise have been eligible for KATHERINE,” he said in an interview.

It’s still unclear, however, whether patients who receive pertuzumab (Perjeta) in the neoadjuvant setting and have residual lymph-node positive or estrogen receptor–negative might benefit with adjuvant therapy with T-DM1 instead of trastuzumab, he said.

“The second question that’s unclear at this time is patients who get 1 year of T-DM1, should they then receive neratinib [Nerlynx], because we have data from the ExteNET trial which showed that patients who complete 1 year of anti-HER2 therapy, if they receive 1 year of neratinib, there’s also reduced risk of recurrence, and that’s an unknown question at this time,” Dr. Bardia said.

The trial was funded by Hoffman–La Roche/Genentech. Dr. Geyer reported travel support from Roche and AstraZeneca, medical writing support from AbbVie and Roche, and honoraria from Celgene. Dr. Winer reported receiving grants for clinical research from and has served as an adviser or consultant to Genentech, AstraZeneca, Pfizer, and GlaxoSmithKline. Dr. Bardia reported relationships with Genentech and Novartis.

SOURCE: Geyer CE et al. N Engl J Med. 2018 Dec 5. doi: 10.1056/NEJMoa1814017.

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

This is the final issue of The Journal of Community and Supportive Oncology. Since our launch – separately as the Journal of Supportive Oncology in 2003 and Community Oncology in 2004 – and through the 2014 merger to form JCSO, our purpose has always been to connect with practice-based caregivers and to provide them with carefully selected, peer-reviewed information that could easily be incorporated into daily practice. Our overarching goal was to help ensure the delivery of the best-possible care and outcomes for our patients. We hope we achieved that, and the results of a 2016 readership survey seemed to confirm as much. But from a business perspective, and especially with the transition to online publishing and intensely competitive advertising landscape, economic survival became increasingly elusive, and management decided to close the journal.

Looking ahead

From January 2019, JCSO’s sister publications, Hematology News and Oncology Practice, will reside on a shared digital platform, MDedge Oncology, that will focus on news and conference coverage. Archives for JCSO, JSO, and Community Oncology will be available on this new platform at www.mdedge.com/oncology after the launch. In addition, I will host a weekly podcast focusing on current trends and advances in clinical and supportive care. It will include a long-form interview with an expert in oncology, along the lines of the former JCSO Interview, and with short end-segments on patient care, translating new research to daily practice, and a monthly journal round-up. You'll be able to subscribe to and download it at Apple podcasts, using the search terms HemOnc and MDedge.
 

In this issue

We end with a bumper crop of articles, beginning with a report by Hedden and colleagues on page e234 describing how they developed, implemented, and evaluated a supportive care program for patients with prostate cancer. That is followed by a literature-based review article by Ibrahim colleagues detailing the effectiveness of duloxetine in the treatment of painful chemotherapy-induced peripheral neuropathy (p. e243). In the original research section, on page e250, Palmisiano and colleagues report on mortality outcomes in hospitalized patients with cancer after rapid response team activation; Jeurkar and colleagues compare risk models guiding growth factor use in chemotherapy (p. e256); and Chao and colleagues describe the symptom burdens associated with chemotherapy-induced anemia in patients with late-stage cancer (e260).

Challenging and elusive are the key words in this issue's Case Reports in which Pollock and colleagues describe the difficulties in managing a cetuximab rash (p. e272), Roberts and colleagues write about elevated liver function tests in a patient on palbociclib and fulvestrant (p. e277), and Mukherjee and colleagues describe a patient with intravascular large B-cell lymphoma, who presented both a diagnostic and management challenge for the care team (p. e280). Turn to page e283, where our regular contributor, Jane de Lartigue, has written an in-depth review on everything you need to know about biosimilars. Susan London follows up on page e290 with an article on findings from studies on biosimilars for 3 oncology drugs that were reported at this year’s annual meeting of the American Society of Clinical Oncology. Dr de Lartigue also reports on the approval of dabrafenib and trametinib for BRAF-mutant melanoma (e228) and osimertinib for advanced non–small-cell lung cancer (p. e231).

And finally…

I wish you and your colleagues and families all good things for the coming year. Thank you and goodbye – and stay in touch by downloading my podcast!

It is that time of year when federal compliance officers, clinical ethicists, and staff counsels are flooded with queries about the legal and ethical acceptability of gifts. And no wonder, all the winter holidays often involve giving gifts. The simple and spontaneous acts of giving and receiving gifts become more complicated and deliberative in the federal health care system. Both legal rules and ethical values bear upon who can offer and accept what gift to whom upon what occasion and in what amount. The “Standards of Ethical Conduct for Employees of the Executive Branch” devotes 2 entire subparts to the subject of gifts.¹ We will examine a small section of the document that can become a big issue for federal practitioners during that holiday—gifts from patients.

First, veterans (patients) are “prohibited sources” in section 5 CFR §2635.203 (d).¹ And since VA employees are subject to restrictions on accepting gifts from sources outside the government, unless an exception applies, federal employees may not accept a gift because of their official position (eg, Federal Practitioner, editor-in-chief) or a gift from a patient (prohibited source; [5 CFR §2635.201]).

It might seem like this is going to be a very short column this month, as gifts from patients are forbidden. Yet, a Christmas card or homemade fudge isn’t really a gift, is it?
5 CFR §2635.203 (b) defines what is and is not a gift: For example, minor items of food or items like a thank-you card are specifically excluded in section (b) 1-10.

Is Christmas an exception or are just types of gifts excluded?
There are exceptions to the general regulation about accepting gifts from prohibited sources. Many staff will recall hearing about the “$20 rule,” which is actually the “$20-50” rule stating that a federal employee may accept a gift from a patient (prohibited source) if the value of said gift is under $20 and the employee does not accept more than $50 from any single source in a calendar year. §2635.204 lists the exceptions. However, starting in 2017, the regulations changed to require that federal employees also consider not just whether they could accept a gift but—ethically—they should take the gift even if it was permitted under the law. The Office of Government Ethics made this change because it wanted to emphasize the importance of considering not just how things are but how things appear to be. The regulations contain detailed descriptions of what employees should think about and stipulates that the decisions will not be further scrutinized (5 CFR §2635.201[b]).¹

Based on this new emphasis on appearances, ethically, no doctor or nurse should accept the keys to a new BMW from a patient who owns a luxury car dealership. But what about more prosaic and probable presents: the holiday cookies a single father made with his children for the nurse practitioner who has been his primary care practitioner for years; the birdhouse a Vietnam veteran made in her crafts class for the surgeon who removed her gallbladder; or even the store-bought but no less heartfelt tin of popcorn from an elderly veteran for the hospitalist who saw him through a rough bought of pneumonia?

Related: Happy Federal New Year

The rules about practitioners accepting patient gifts are rational and unambiguous: It is the values conflict surrounding patient gifts that is often emotion driven and muddled; it may be easier and safer to adopt the “just say no” policy. And yet, while this might seem the most unassailable position to avoid a conflict of interest, could this possibly be a more practitioner- than patient-centered standard? Authoritative sources in the ethics literature are equally divided and ambivalent on the question.^2,3 The American College of Physicians Ethics Manual states: “In deciding whether to accept a gift from a patient, the physician should consider the nature of the gift and its value to the patient, the potential implications for the patient-physician relationship of accepting or refusing it, and the patient’s probable intention and expectations.”⁴ A small gift as a token of appreciation is not ethically problematic. Favored treatment as a result of acceptance of any gift is problematic, undermines professionalism, and may interfere with objectivity in the care of the patient.⁴

Related: Am I My Brother’s/Sister’s Keeper?

Many an ethics commentator have cautioned, “beware of patients bearing gifts.”⁵ In making an ethical assessment of whether or not to accept the gift, a key question a practitioner needs to ask him or herself is about the patient’s motive. Even the patient may be unaware of the reasons behind their giving, and the wise practitioner will take a mindful moment to think about the context and timing of the gift and the nature of his or her relationship to the patient. Sadly, many of our patients are lonely especially at this family time of year and on some level may hope the gift will help slide the professional relationship toward a more personal one. Some patients may think a gift might earn them preferential treatment. Finally, a few patients may have a romantic or sexual attraction toward a clinician.

Often in the latter 2 cases, a pattern will develop that discloses the patient’s true intent. Very expensive gifts, monetary gifts, excessively personal gifts, or frequent gifts should alert the practitioner that more may be going on. A kind reminder to the patient that providing good care is the only reward needed may be sufficient. For practitioners whose ethical code does not permit them to accept gifts, then a genuine thank you and an explanation of the rules and/or values behind the refusal may be necessary. There are other times when the practitioner or a supervisor/advisor may need to reset the boundaries or even to transfer the patient to another practitioner. The norms in mental health care and psychotherapy are more stringent because of the intimacy of the relationship and the potential vulnerability of patients.⁶

For gifts that seem genuine and generous or cost a trivial amount, then there is an ethical argument to be made for accepting them with gratitude. In many cultures, hospitality is a tradition, and expressing appreciation a virtue, so when a practitioner refuses to graciously take a small gift, they risk offending the patient. Rejection of a gift can be seen as disrespectful and could cause a rupture in an otherwise sound practitioner-patient relationship. Other patients experience strong feelings of gratitude and admiration for their practitioners, stronger than most of us recognize. The ability for a patient to give their practitioner a holiday gift, particularly one they invested time and energy in creating or choosing, can enhance their sense of self-worth and individual agency. These gifts are not so much an attempt to diminish the professional power differential but to close the gap between 2 human beings in an unequal relationship that is yet one of shared decision making. All practitioners should be aware of the often underappreciated social power of a gift to influence decisions.

Related: Caring Under a Microscope

At the same time, clinicians can strive to be sensitively attuned to the reality that, sometimes the cookie is just a cookie so eat and enjoy, just remember to share with your group. External judgments are often cited as practical rules of thumb for determining the ethical acceptability of a gift: Would you want your mother, newspaper, or colleague to know you took the present? I prefer an internal moral compass that steers always to the true north of is accepting this gift really in the patient’s best interest?

It is that time of year when federal compliance officers, clinical ethicists, and staff counsels are flooded with queries about the legal and ethical acceptability of gifts. And no wonder, all the winter holidays often involve giving gifts. The simple and spontaneous acts of giving and receiving gifts become more complicated and deliberative in the federal health care system. Both legal rules and ethical values bear upon who can offer and accept what gift to whom upon what occasion and in what amount. The “Standards of Ethical Conduct for Employees of the Executive Branch” devotes 2 entire subparts to the subject of gifts.¹ We will examine a small section of the document that can become a big issue for federal practitioners during that holiday—gifts from patients.

First, veterans (patients) are “prohibited sources” in section 5 CFR §2635.203 (d).¹ And since VA employees are subject to restrictions on accepting gifts from sources outside the government, unless an exception applies, federal employees may not accept a gift because of their official position (eg, Federal Practitioner, editor-in-chief) or a gift from a patient (prohibited source; [5 CFR §2635.201]).

It might seem like this is going to be a very short column this month, as gifts from patients are forbidden. Yet, a Christmas card or homemade fudge isn’t really a gift, is it?
5 CFR §2635.203 (b) defines what is and is not a gift: For example, minor items of food or items like a thank-you card are specifically excluded in section (b) 1-10.

Is Christmas an exception or are just types of gifts excluded?
There are exceptions to the general regulation about accepting gifts from prohibited sources. Many staff will recall hearing about the “$20 rule,” which is actually the “$20-50” rule stating that a federal employee may accept a gift from a patient (prohibited source) if the value of said gift is under $20 and the employee does not accept more than $50 from any single source in a calendar year. §2635.204 lists the exceptions. However, starting in 2017, the regulations changed to require that federal employees also consider not just whether they could accept a gift but—ethically—they should take the gift even if it was permitted under the law. The Office of Government Ethics made this change because it wanted to emphasize the importance of considering not just how things are but how things appear to be. The regulations contain detailed descriptions of what employees should think about and stipulates that the decisions will not be further scrutinized (5 CFR §2635.201[b]).¹

Based on this new emphasis on appearances, ethically, no doctor or nurse should accept the keys to a new BMW from a patient who owns a luxury car dealership. But what about more prosaic and probable presents: the holiday cookies a single father made with his children for the nurse practitioner who has been his primary care practitioner for years; the birdhouse a Vietnam veteran made in her crafts class for the surgeon who removed her gallbladder; or even the store-bought but no less heartfelt tin of popcorn from an elderly veteran for the hospitalist who saw him through a rough bought of pneumonia?

Related: Happy Federal New Year

The rules about practitioners accepting patient gifts are rational and unambiguous: It is the values conflict surrounding patient gifts that is often emotion driven and muddled; it may be easier and safer to adopt the “just say no” policy. And yet, while this might seem the most unassailable position to avoid a conflict of interest, could this possibly be a more practitioner- than patient-centered standard? Authoritative sources in the ethics literature are equally divided and ambivalent on the question.^2,3 The American College of Physicians Ethics Manual states: “In deciding whether to accept a gift from a patient, the physician should consider the nature of the gift and its value to the patient, the potential implications for the patient-physician relationship of accepting or refusing it, and the patient’s probable intention and expectations.”⁴ A small gift as a token of appreciation is not ethically problematic. Favored treatment as a result of acceptance of any gift is problematic, undermines professionalism, and may interfere with objectivity in the care of the patient.⁴

Related: Am I My Brother’s/Sister’s Keeper?

Many an ethics commentator have cautioned, “beware of patients bearing gifts.”⁵ In making an ethical assessment of whether or not to accept the gift, a key question a practitioner needs to ask him or herself is about the patient’s motive. Even the patient may be unaware of the reasons behind their giving, and the wise practitioner will take a mindful moment to think about the context and timing of the gift and the nature of his or her relationship to the patient. Sadly, many of our patients are lonely especially at this family time of year and on some level may hope the gift will help slide the professional relationship toward a more personal one. Some patients may think a gift might earn them preferential treatment. Finally, a few patients may have a romantic or sexual attraction toward a clinician.

Often in the latter 2 cases, a pattern will develop that discloses the patient’s true intent. Very expensive gifts, monetary gifts, excessively personal gifts, or frequent gifts should alert the practitioner that more may be going on. A kind reminder to the patient that providing good care is the only reward needed may be sufficient. For practitioners whose ethical code does not permit them to accept gifts, then a genuine thank you and an explanation of the rules and/or values behind the refusal may be necessary. There are other times when the practitioner or a supervisor/advisor may need to reset the boundaries or even to transfer the patient to another practitioner. The norms in mental health care and psychotherapy are more stringent because of the intimacy of the relationship and the potential vulnerability of patients.⁶

For gifts that seem genuine and generous or cost a trivial amount, then there is an ethical argument to be made for accepting them with gratitude. In many cultures, hospitality is a tradition, and expressing appreciation a virtue, so when a practitioner refuses to graciously take a small gift, they risk offending the patient. Rejection of a gift can be seen as disrespectful and could cause a rupture in an otherwise sound practitioner-patient relationship. Other patients experience strong feelings of gratitude and admiration for their practitioners, stronger than most of us recognize. The ability for a patient to give their practitioner a holiday gift, particularly one they invested time and energy in creating or choosing, can enhance their sense of self-worth and individual agency. These gifts are not so much an attempt to diminish the professional power differential but to close the gap between 2 human beings in an unequal relationship that is yet one of shared decision making. All practitioners should be aware of the often underappreciated social power of a gift to influence decisions.

Related: Caring Under a Microscope

At the same time, clinicians can strive to be sensitively attuned to the reality that, sometimes the cookie is just a cookie so eat and enjoy, just remember to share with your group. External judgments are often cited as practical rules of thumb for determining the ethical acceptability of a gift: Would you want your mother, newspaper, or colleague to know you took the present? I prefer an internal moral compass that steers always to the true north of is accepting this gift really in the patient’s best interest?

It is that time of year when federal compliance officers, clinical ethicists, and staff counsels are flooded with queries about the legal and ethical acceptability of gifts. And no wonder, all the winter holidays often involve giving gifts. The simple and spontaneous acts of giving and receiving gifts become more complicated and deliberative in the federal health care system. Both legal rules and ethical values bear upon who can offer and accept what gift to whom upon what occasion and in what amount. The “Standards of Ethical Conduct for Employees of the Executive Branch” devotes 2 entire subparts to the subject of gifts.¹ We will examine a small section of the document that can become a big issue for federal practitioners during that holiday—gifts from patients.

First, veterans (patients) are “prohibited sources” in section 5 CFR §2635.203 (d).¹ And since VA employees are subject to restrictions on accepting gifts from sources outside the government, unless an exception applies, federal employees may not accept a gift because of their official position (eg, Federal Practitioner, editor-in-chief) or a gift from a patient (prohibited source; [5 CFR §2635.201]).

It might seem like this is going to be a very short column this month, as gifts from patients are forbidden. Yet, a Christmas card or homemade fudge isn’t really a gift, is it?
5 CFR §2635.203 (b) defines what is and is not a gift: For example, minor items of food or items like a thank-you card are specifically excluded in section (b) 1-10.

Is Christmas an exception or are just types of gifts excluded?
There are exceptions to the general regulation about accepting gifts from prohibited sources. Many staff will recall hearing about the “$20 rule,” which is actually the “$20-50” rule stating that a federal employee may accept a gift from a patient (prohibited source) if the value of said gift is under $20 and the employee does not accept more than $50 from any single source in a calendar year. §2635.204 lists the exceptions. However, starting in 2017, the regulations changed to require that federal employees also consider not just whether they could accept a gift but—ethically—they should take the gift even if it was permitted under the law. The Office of Government Ethics made this change because it wanted to emphasize the importance of considering not just how things are but how things appear to be. The regulations contain detailed descriptions of what employees should think about and stipulates that the decisions will not be further scrutinized (5 CFR §2635.201[b]).¹

Based on this new emphasis on appearances, ethically, no doctor or nurse should accept the keys to a new BMW from a patient who owns a luxury car dealership. But what about more prosaic and probable presents: the holiday cookies a single father made with his children for the nurse practitioner who has been his primary care practitioner for years; the birdhouse a Vietnam veteran made in her crafts class for the surgeon who removed her gallbladder; or even the store-bought but no less heartfelt tin of popcorn from an elderly veteran for the hospitalist who saw him through a rough bought of pneumonia?

Related: Happy Federal New Year

The rules about practitioners accepting patient gifts are rational and unambiguous: It is the values conflict surrounding patient gifts that is often emotion driven and muddled; it may be easier and safer to adopt the “just say no” policy. And yet, while this might seem the most unassailable position to avoid a conflict of interest, could this possibly be a more practitioner- than patient-centered standard? Authoritative sources in the ethics literature are equally divided and ambivalent on the question.^2,3 The American College of Physicians Ethics Manual states: “In deciding whether to accept a gift from a patient, the physician should consider the nature of the gift and its value to the patient, the potential implications for the patient-physician relationship of accepting or refusing it, and the patient’s probable intention and expectations.”⁴ A small gift as a token of appreciation is not ethically problematic. Favored treatment as a result of acceptance of any gift is problematic, undermines professionalism, and may interfere with objectivity in the care of the patient.⁴

Related: Am I My Brother’s/Sister’s Keeper?

Many an ethics commentator have cautioned, “beware of patients bearing gifts.”⁵ In making an ethical assessment of whether or not to accept the gift, a key question a practitioner needs to ask him or herself is about the patient’s motive. Even the patient may be unaware of the reasons behind their giving, and the wise practitioner will take a mindful moment to think about the context and timing of the gift and the nature of his or her relationship to the patient. Sadly, many of our patients are lonely especially at this family time of year and on some level may hope the gift will help slide the professional relationship toward a more personal one. Some patients may think a gift might earn them preferential treatment. Finally, a few patients may have a romantic or sexual attraction toward a clinician.

Often in the latter 2 cases, a pattern will develop that discloses the patient’s true intent. Very expensive gifts, monetary gifts, excessively personal gifts, or frequent gifts should alert the practitioner that more may be going on. A kind reminder to the patient that providing good care is the only reward needed may be sufficient. For practitioners whose ethical code does not permit them to accept gifts, then a genuine thank you and an explanation of the rules and/or values behind the refusal may be necessary. There are other times when the practitioner or a supervisor/advisor may need to reset the boundaries or even to transfer the patient to another practitioner. The norms in mental health care and psychotherapy are more stringent because of the intimacy of the relationship and the potential vulnerability of patients.⁶

For gifts that seem genuine and generous or cost a trivial amount, then there is an ethical argument to be made for accepting them with gratitude. In many cultures, hospitality is a tradition, and expressing appreciation a virtue, so when a practitioner refuses to graciously take a small gift, they risk offending the patient. Rejection of a gift can be seen as disrespectful and could cause a rupture in an otherwise sound practitioner-patient relationship. Other patients experience strong feelings of gratitude and admiration for their practitioners, stronger than most of us recognize. The ability for a patient to give their practitioner a holiday gift, particularly one they invested time and energy in creating or choosing, can enhance their sense of self-worth and individual agency. These gifts are not so much an attempt to diminish the professional power differential but to close the gap between 2 human beings in an unequal relationship that is yet one of shared decision making. All practitioners should be aware of the often underappreciated social power of a gift to influence decisions.

Related: Caring Under a Microscope

At the same time, clinicians can strive to be sensitively attuned to the reality that, sometimes the cookie is just a cookie so eat and enjoy, just remember to share with your group. External judgments are often cited as practical rules of thumb for determining the ethical acceptability of a gift: Would you want your mother, newspaper, or colleague to know you took the present? I prefer an internal moral compass that steers always to the true north of is accepting this gift really in the patient’s best interest?

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In the past decade, breastfeeding rates have increased substantially. Between 2000 and 2015, the proportion of infants who continued to breastfeed at 12 months increased from 16% to 36%. The proportion of infants who had any breastfeeding increased from 71% to 83%.¹ While the infant health benefits of breastfeeding are widely recognized, the maternal health benefits of breastfeeding are many and likely underappreciated.

Infant health benefits of breastfeeding

There are no large-scale, randomized studies of the long-term health benefits of breastfeeding versus formula feeding. The evidence supporting the health benefits of breastfeeding is derived from case-control and cohort studies. Breastfeeding directly benefits newborn and infant nutrition, gastrointestinal function, host defense, and psychological well-being. Compared with formula-fed newborns, breastfed infants have a reduced risk of infectious diseases including otitis media, gastroenteritis, respiratory infections, sudden infant death syndrome, and metabolic disease. These benefits alone strongly support the public health benefit of breastfeeding.² In addition, breastfeeding greatly benefits maternal health.

Maternal health benefits of breastfeeding

Breastfeeding reduces a woman’s risk for type 2 diabetes, hypertension, and coronary artery disease, myocardial infarction, as well as breast, ovarian, and endometrial cancer. There are few exposures that have such a multitude of positive health benefits.

filler 

Type 2 diabetes

In a prospective cohort study of 1,238 women without diabetes in 1985–1986, 182 women developed type 2 diabetes after 30 years of follow-up. Compared with never breastfeeding, breastfeeding for 0 to 6 months, >6 months to <12 months, or ≥12 months reduced the risk of type 2 diabetes by 25%, 48%, and 69% respectively.³ In the prospective Nurses’ Health Study, among parous women, each additional year of breastfeeding decreased the risk of type 2 diabetes by 15% compared with women who did not breastfeed.⁴

Hypertension

In the Women’s Health Initiative (WHI) study of postmenopausal women, a lifetime history of breastfeeding for 12 months or more was associated with a 12% decrease in the risk of hypertension.⁵ For parous women, the prevalence of hypertension among breastfeeding (≥12 months) and never breastfeeding women was estimated to be 38.6% versus 42.1%.⁵ Similar results were observed in the Nurses’ Health Study II.⁶

Myocardial infarction and coronary heart disease

In the prospective Nurses’ Health Study, during 1,350,965 person-years of follow-up, 2,540 women had a myocardial infarction (MI). Women who had breastfed for ≥ 2 years had a 37% decreased risk of MI compared with women who never breastfed. After adjustment for family history, lifestyle factors, and adiposity, the observed reduction in risk was 23%.⁷ In the WHI (observational study plus controlled trial), women with a single live birth who breastfed for 7 to 12 months had a lower risk of cardiovascular disease than women with a single live birth who did not breastfeed (hazard ratio, 0.72; 95% confidence interval, 0.53–97).⁵

Breast cancer

In a systematic review and meta-analysis of 100 publications, breastfeeding >12 months reduced the risk of breast cancer by 26%.⁸ In a systematic review of 47 studies, the relative risk of breast cancer decreased by 4.7% for every 12 months of breastfeeding.⁹ In a systematic review and meta-analysis of 3 studies, ever breastfeeding was associated with a 28% reduced risk for triple-negative (ER-, PR-, HER2-) breast cancer among parous women.¹⁰ Triple-negative breast cancer generally has a poorer prognosis than receptor-positive breast cancers.

Continue to: Ovarian Cancer

In a systematic review and meta-analysis of 40 publications, ever breastfeeding was associated with a 37% reduction in the risk of ovarian cancer.⁸ In a prospective study of 1.1 million women in the United Kingdom, 8,719 developed ovarian cancer. Among parous women, ovarian cancer risk was reduced by 10% for every 12 months of breastfeeding.¹¹

Endometrial cancer

In a meta-analysis of 17 publications, including 8,981 cases and 17,241 controls, ever breastfeeding was associated with an 11% reduction in breast cancer risk.¹² In a meta-analysis of 15 publications with 6,704 cases, breastfeeding was associated with a 26% reduction in endometrial cancer. After controlling for hormone use and body mass index, the reduced risk was in the range of 35%. A linear relationship between breastfeeding and reduced risk of endometrial cancer was observed, with 1 month of breastfeeding being associated with a 1.2% reduction in the risk of endometrial cancer.¹³

Let’s support our patients’ health by encouraging successful breastfeeding

Obstetrician-gynecologists play an important role in helping women make informed decisions about breastfeeding. Most professional organizations, including the American College of Obstetricians and Gynecologists, recommend exclusive breastfeeding for the first 6 months of life, with continued breastfeeding and introduction of complementary food from 6 to 12 months.^14,15 Birth practices that help to increase successful breastfeeding include:

• inform all pregnant women about the newborn and maternal health benefits and management of breastfeeding
• initiate skin-to-skin contact at birth
• encourage the initiation of breastfeeding within 1 hour of birth
• ensure that breastfeeding newborns do not receive any food or drink other than breast milk, unless medically indicated
• encourage breastfeeding women to not use pacifiers or artificial nipples.¹⁵

When women are discharged from the maternity center, providing information about community-based lactation support is helpful in ensuring continuation of successful breastfeeding.¹⁶

Most patients know that exercise and maintaining a healthy weight can reduce the risk of developing many prevalent diseases. However, far fewer patients know that breastfeeding can reduce the risk of developing type 2 diabetes, hypertension, and coronary artery disease, as well as breast, ovarian, and endometrial cancers. Educating our patients about these health benefits may help them to more fully commit to breastfeeding.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

There was no significant difference in mortality between critically ill patients who received pantoprazole prophylaxis for gastrointestinal bleeding, and those who received placebo, new findings suggest.

In a multicenter, randomized trial of 3,298 adult patients at risk for gastrointestinal bleeding, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died at 90 days (relative risk, 1.02; 95% confidence interval, 0.91-1.13; P = .76). The results were published in the New England Journal of Medicine.

Patients were aged 18 years or older; had been admitted to the ICU for an acute condition in one of six international centers; and had at least one risk factor for gastrointestinal bleeding including shock, use of anticoagulant agents, renal replacement therapy, mechanical ventilation (expected to last more than 24 hours), any history of liver disease, or any history of or ongoing coagulopathy. A total of 1,645 patients were randomly assigned to receive 40 mg of intravenous pantoprazole once daily and 1,653 received placebo, reported Mette Krag, MD, of the department of intensive care at Rigshospitalet in Copenhagen, and her coauthors.

The primary outcome was 90-day mortality. Secondary outcomes were clinically important events in the ICU, clinically important gastrointestinal bleeding in the ICU, infectious adverse events in the ICU, and days alive without the use of life support within the 90-day period.

One or more clinically important events occurred in 21.9% of patients in the pantoprazole group and in 22.6% in the placebo group (RR, 0.96; 95% CI, 0.83-1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, compared with 4.2% in the placebo group, Dr. Krag and her coauthors wrote.

The findings are similar to other recently published results, which showed “no significant differences ... in the rates of death or infectious complications between patients receiving placebo or no prophylaxis and those receiving proton pump inhibitors,” the authors wrote.

Dr. Krag reported financial support from Innovation Fund Denmark, Ehrenreich’s Foundation, and several other organizations.

SOURCE: Krag M et al. N Engl J Med. 2018 Dec 6. doi: 10.1056/NEJMoa1714919.

This article was updated 12/6/18.

The FP recognized the severely sun damaged scalp as a major risk factor for skin cancers. He looked closely at the lesions and realized that the ulcerated areas were at particularly high risk for squamous cell carcinoma (SCC).

He performed broad shave biopsies with sufficient depth to obtain the needed diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The pathology demonstrated that 2 of the 3 biopsy sites were positive for SCC (E and G were SCC, while F was read as actinic keratosis). Cutaneous SCC is a malignant tumor of keratinocytes. Most cutaneous SCCs arise from precursor lesions, often actinic keratoses. SCC usually spreads by local extension, but it is also capable of regional lymph node metastasis and distant metastasis.

Unsure of the margins of the tumors and aware that surgery of the scalp can be challenging, the FP referred the patient for Mohs surgery. The FP also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

The Mohs surgeon recommended field treatment with 5% fluorouracil cream twice daily for 4 weeks before surgery to minimize the amount of cutting that would be needed to clear the SCC from this diffusely sun-damaged scalp. After the 5% fluorouracil cream treatment, the surgeon waited 1 month to allow the scalp to heal before performing surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized the severely sun damaged scalp as a major risk factor for skin cancers. He looked closely at the lesions and realized that the ulcerated areas were at particularly high risk for squamous cell carcinoma (SCC).

He performed broad shave biopsies with sufficient depth to obtain the needed diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The pathology demonstrated that 2 of the 3 biopsy sites were positive for SCC (E and G were SCC, while F was read as actinic keratosis). Cutaneous SCC is a malignant tumor of keratinocytes. Most cutaneous SCCs arise from precursor lesions, often actinic keratoses. SCC usually spreads by local extension, but it is also capable of regional lymph node metastasis and distant metastasis.

Unsure of the margins of the tumors and aware that surgery of the scalp can be challenging, the FP referred the patient for Mohs surgery. The FP also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

The Mohs surgeon recommended field treatment with 5% fluorouracil cream twice daily for 4 weeks before surgery to minimize the amount of cutting that would be needed to clear the SCC from this diffusely sun-damaged scalp. After the 5% fluorouracil cream treatment, the surgeon waited 1 month to allow the scalp to heal before performing surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized the severely sun damaged scalp as a major risk factor for skin cancers. He looked closely at the lesions and realized that the ulcerated areas were at particularly high risk for squamous cell carcinoma (SCC).

He performed broad shave biopsies with sufficient depth to obtain the needed diagnosis. (See the Watch & Learn video on “Shave biopsy.”) The pathology demonstrated that 2 of the 3 biopsy sites were positive for SCC (E and G were SCC, while F was read as actinic keratosis). Cutaneous SCC is a malignant tumor of keratinocytes. Most cutaneous SCCs arise from precursor lesions, often actinic keratoses. SCC usually spreads by local extension, but it is also capable of regional lymph node metastasis and distant metastasis.

Unsure of the margins of the tumors and aware that surgery of the scalp can be challenging, the FP referred the patient for Mohs surgery. The FP also provided counseling about sun avoidance, the consistent use of a hat outdoors, and the use of sunscreens when exposed to the sun.

The Mohs surgeon recommended field treatment with 5% fluorouracil cream twice daily for 4 weeks before surgery to minimize the amount of cutting that would be needed to clear the SCC from this diffusely sun-damaged scalp. After the 5% fluorouracil cream treatment, the surgeon waited 1 month to allow the scalp to heal before performing surgery.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

The new third edition will be available in January 2019: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/.

You can also get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.

Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.

“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).

Bevacizumab biosimilar

The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.

The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).

Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.

Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).

“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”

Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999

Trastuzumab biosimilar

The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.

The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.

Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.

Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”

The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.

“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.

“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”

Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”

Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
 

Filgrastim biosimilar

Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.

Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).

Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.

Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.

The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”

Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.

“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
 

Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700

Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.

Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.

“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).

Bevacizumab biosimilar

The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.

The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).

Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.

Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).

“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”

Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999

Trastuzumab biosimilar

The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.

The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.

Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.

Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”

The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.

“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.

“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”

Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”

Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
 

Filgrastim biosimilar

Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.

Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).

Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.

Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.

The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”

Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.

“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
 

Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700

Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.

Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.

“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).

Bevacizumab biosimilar

The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.

The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).

Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.

Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).

“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”

Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999

Trastuzumab biosimilar

The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.

The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.

Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.

Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”

The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.

“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.

“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”

Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”

Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
 

Filgrastim biosimilar

Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.

Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).

Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.

Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.

The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”

Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.

“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
 

Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700