Hormonal intrauterine devices inserted immediately postpartum had a nearly six times greater likelihood of expulsion compared with copper IUDs, but most women who requested any type of long-acting reversible contraception (LARC) postpartum were still using it half a year later, a recent study found.

“With more than eight out of ten women continuing use at 6 months, in-hospital placement of postpartum LARC devices is a worthwhile intervention,” reported Jennifer L. Eggebroten, MD, and her associates at the University of Utah. “More than half of women who experienced IUD expulsion without commencement of another highly effective contraceptive went on to become pregnant within 2 years, highlighting the need for appropriate counseling prior to device placement and backup contraception planning.”

flocu/ThinkStock

Hormonal intrauterine devices inserted immediately postpartum had a nearly six times greater likelihood of expulsion compared with copper IUDs, but most women who requested any type of long-acting reversible contraception (LARC) postpartum were still using it half a year later, a recent study found.

“With more than eight out of ten women continuing use at 6 months, in-hospital placement of postpartum LARC devices is a worthwhile intervention,” reported Jennifer L. Eggebroten, MD, and her associates at the University of Utah. “More than half of women who experienced IUD expulsion without commencement of another highly effective contraceptive went on to become pregnant within 2 years, highlighting the need for appropriate counseling prior to device placement and backup contraception planning.”

flocu/ThinkStock

Hormonal intrauterine devices inserted immediately postpartum had a nearly six times greater likelihood of expulsion compared with copper IUDs, but most women who requested any type of long-acting reversible contraception (LARC) postpartum were still using it half a year later, a recent study found.

“With more than eight out of ten women continuing use at 6 months, in-hospital placement of postpartum LARC devices is a worthwhile intervention,” reported Jennifer L. Eggebroten, MD, and her associates at the University of Utah. “More than half of women who experienced IUD expulsion without commencement of another highly effective contraceptive went on to become pregnant within 2 years, highlighting the need for appropriate counseling prior to device placement and backup contraception planning.”

flocu/ThinkStock

PHILADELPHIA – There is a long list of benefits from bariatric surgery in the morbidly obese, but prevention of end-stage liver disease and the need for a first or second liver transplant is likely to grow as an indication, according to an overview of weight loss surgery at Digestive Diseases: New Advances, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.

“Bariatric surgery is associated with significant improvement not just in diabetes, dyslipidemia, hypertension, and other complications of metabolic disorders but for me more interestingly, it is effective for treating fatty liver disease where you can see a 90% improvement in steatosis,” reported Subhashini Ayloo, MD, chief of minimally invasive robotic hepato-pancreato-biliary surgery and liver transplantation at New Jersey Medical School, Newark.

Trained in both bariatric surgery and liver transplant, Dr. Ayloo predicts that these fields will become increasingly connected because of the obesity epidemic and the related rise in nonalcoholic fatty liver disease (NAFLD). Dr. Ayloo reported that bariatric surgery is already being used in her center to avoid a second liver transplant in obese patients who are unable to lose sufficient weight to prevent progressive NAFLD after a first transplant.

Courtesy of Wikimedia / Nephron / Creative Commons License

Global Academy and this news organization are owned by the same company. Dr. Ayloo reports no relevant financial relationships.

AGA Resource

The AGA Obesity Practice Guide provides tools for gastroenterologists to lead a multidisciplinary team of health-care professionals for the management of patients with obesity. Learn more at www.gastro.org/obesity.

PHILADELPHIA – There is a long list of benefits from bariatric surgery in the morbidly obese, but prevention of end-stage liver disease and the need for a first or second liver transplant is likely to grow as an indication, according to an overview of weight loss surgery at Digestive Diseases: New Advances, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.

“Bariatric surgery is associated with significant improvement not just in diabetes, dyslipidemia, hypertension, and other complications of metabolic disorders but for me more interestingly, it is effective for treating fatty liver disease where you can see a 90% improvement in steatosis,” reported Subhashini Ayloo, MD, chief of minimally invasive robotic hepato-pancreato-biliary surgery and liver transplantation at New Jersey Medical School, Newark.

Trained in both bariatric surgery and liver transplant, Dr. Ayloo predicts that these fields will become increasingly connected because of the obesity epidemic and the related rise in nonalcoholic fatty liver disease (NAFLD). Dr. Ayloo reported that bariatric surgery is already being used in her center to avoid a second liver transplant in obese patients who are unable to lose sufficient weight to prevent progressive NAFLD after a first transplant.

Courtesy of Wikimedia / Nephron / Creative Commons License

Global Academy and this news organization are owned by the same company. Dr. Ayloo reports no relevant financial relationships.

AGA Resource

The AGA Obesity Practice Guide provides tools for gastroenterologists to lead a multidisciplinary team of health-care professionals for the management of patients with obesity. Learn more at www.gastro.org/obesity.

PHILADELPHIA – There is a long list of benefits from bariatric surgery in the morbidly obese, but prevention of end-stage liver disease and the need for a first or second liver transplant is likely to grow as an indication, according to an overview of weight loss surgery at Digestive Diseases: New Advances, held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education.

“Bariatric surgery is associated with significant improvement not just in diabetes, dyslipidemia, hypertension, and other complications of metabolic disorders but for me more interestingly, it is effective for treating fatty liver disease where you can see a 90% improvement in steatosis,” reported Subhashini Ayloo, MD, chief of minimally invasive robotic hepato-pancreato-biliary surgery and liver transplantation at New Jersey Medical School, Newark.

Trained in both bariatric surgery and liver transplant, Dr. Ayloo predicts that these fields will become increasingly connected because of the obesity epidemic and the related rise in nonalcoholic fatty liver disease (NAFLD). Dr. Ayloo reported that bariatric surgery is already being used in her center to avoid a second liver transplant in obese patients who are unable to lose sufficient weight to prevent progressive NAFLD after a first transplant.

Courtesy of Wikimedia / Nephron / Creative Commons License

Global Academy and this news organization are owned by the same company. Dr. Ayloo reports no relevant financial relationships.

AGA Resource

The AGA Obesity Practice Guide provides tools for gastroenterologists to lead a multidisciplinary team of health-care professionals for the management of patients with obesity. Learn more at www.gastro.org/obesity.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Metal allergy in patients with orthopedic implants can cause serious problems including dermatitis and implant failure.¹ As life expectancy increases, the general population ages, and more metallic orthopedic implants are placed,² allergy to these implants is expected to be a problem of greater significance. Uncertainty remains regarding best practice for patients with suspected metal implant allergy.¹ The major questions are: Who should be tested? When should they be tested? What are the optimal tests to diagnose metal allergy?^3-8

We report the case of a patient with vanadium allergy who developed a diffuse eczematous dermatitis and implant failure after receiving a vanadium-containing titanium alloy orthopedic implant in the left foot. This case is remarkable because hypersensitivity reactions to titanium-based hardware are rare, as they traditionally have not been thought to provoke allergic reactions.⁹

Case Report

A 62-year-old woman who was otherwise healthy presented with an eruption of more than 80 pruritic, nummular, eczematous plaques on the arms, legs, back, and buttocks of 3 weeks’ duration (Figure 1). She had a history of allergy to metal used in costume jewelry. Six weeks prior, the patient underwent implantation of a titanium alloy plate in the left foot for surgical repair of painful deforming osteoarthritis. A radiograph of the foot showed appropriate placement. According to the manufacturer, the plate was composed of the compound Ti6Al4V, which contained 90% titanium, 6% aluminum, and 4% vanadium. The lesions developed on the skin close to but not directly over the surgical site.

A punch biopsy of one of the lesions on the shoulder showed lymphoeosinophilic spongiosis consistent with a delayed hypersensitivity reaction (Figure 2). There was mild clinical improvement of the eruption with topical steroids. A course of prednisone for systemic effect resulted in clearing of the eruption, but it promptly recurred on cessation of the steroids. The patient was then patch tested using the North American 80 Comprehensive Series, with an additional 59 common textile, shampoo, fragrance, and several metal allergens, all of which were negative.

After the hardware was removed, it was analyzed to determine the elemental composition of the plate and screws, and the patient was then patch tested with the major metal components of the implant: aluminum chloride hexahydrate 2.0% pet, elemental titanium 10.0% pet, titanium dioxide 10.0% pet, titanium (III) nitride 5.0% pet, titanium (III) oxalate decahydrate 5.0% pet, elemental vanadium 5.0% pet, and vanadium (III) chloride 1.0% pet. She demonstrated a 1+ reaction (erythema and induration) to vanadium trichloride at 72 and 96 hours.

The plate and screws removed from the patient were sterilized and submitted for analysis. Electron microprobe analysis confirmed that the major elemental composition of the plate and screws essentially matched the manufacturer’s listing (Table 1). The trace elements were determined using laser ablative inductively coupled mass spectroscopy, which demonstrated that the screws were of different metal composition from the plate (Table 2). Electron microprobe analysis also was used to determine the microstructure of the plate and screws. The plate had 2 distinct phases consisting of a titanium-aluminum phase and a vanadium phase, whereas the screw was much more homogeneous. Basic electrochemical studies were performed in a salt solution replicating the tissue of the foot. These studies showed that galvanic corrosion could have occurred between the plate and screws due to the differences of composition.

Comment

Titanium is an attractive metal to use in orthopedic implants. It has a high strength-to-weight ratio, a low modulus of elasticity, and good resistance to corrosion. Titanium can be categorized as either commercially pure titanium (cp-Ti) or a titanium alloy. Colloquially, both cp-Ti and titanium alloys are often referred to simply as titanium, but the distinction is important when it comes to medical implants and devices. Commercially pure titanium is more than 99% pure titanium, but up to 1% of its volume can be comprised of impurities.¹⁰ In titanium alloys, the alloy elements are intentionally added to create a material with optimal properties. The 2 most common types of titanium that are used for orthopedic implants are cp-Ti and Ti6Al4V, a titanium alloy containing approximately 90% titanium, 6% aluminum, and 4% vanadium. Similar to cp-Ti, titanium alloys also can contain impurities such as aluminum, beryllium, cobalt, chromium, iron, nickel, and palladium, among many others. Although these impurities often are considered negligible from a metallurgy perspective, as they do not change the properties of the material, these trace elements may be present in large enough quantities to cause hypersensitivity reactions.¹¹

Several weeks after implantation of a titanium alloy metal plate in the left foot, a widespread eczematous eruption developed in our patient who had no prior skin disease. The eruption was steroid responsive but did not clear until the plate was removed. Detailed metallurgy analysis confirmed that vanadium was present and was not homogeneously distributed in the plate. The plate also was different in composition from the screws. Additional studies showed that galvanic corrosion between the plate and the chemically different screws might have contributed to the release of vanadium in the tissue.

Vanadium is known to be allergenic, especially in the presence of implant failure.^12,13 In our patient, patch testing with more than 100 allergens was negative, except for vanadium trichloride 1%. Our patient’s presentation strongly suggested that she developed a vanadium allergy manifesting as systemic allergic contact dermatitis. She demonstrated no history of skin disease, a widespread eczematous eruption after exposure, histology consistent with systemic contact allergy, a positive patch test to vanadium, and clearance of the eruption on removal of the antigen, which have been proposed as objective criteria that support a diagnosis of metal implant allergy.¹⁴ She refused our suggestion to reimplant a portion of the remaining plate under the skin without screws and monitor for recurrence of the eruption. She did not have a lesion overlying the surgical site, but she did develop lesions near the surgical scar. The literature indicates that cutaneous manifestations of allergy to metallic implants can be both localized and generalized.¹⁴

Although reports are rare, other researchers have found vanadium allergy in patients with metal orthopedic implants.^5,12,13,15 The scarcity of literature on vanadium allergy seems to suggest that it is a rare entity, but we believe that it may be more common. Vanadium allergy may be underdiagnosed because it is not a standard patch test allergen. Furthermore, many of those who do choose to test for it use what we believe to be ineffective formulas of vanadium when patch testing patients. Our patient demonstrated a positive patch test reaction only to vanadium trichloride and not to pure vanadium, which is consistent with the small number of other studies that investigated vanadium allergy.^5,12,13,15 We believe that vanadium trichloride is more water soluble than elemental vanadium,¹⁶ and thus more likely to identify true vanadium allergy than other test materials.

Although reports of vanadium allergy in patients with metal implants are rare in the medical literature, the material science literature clearly states that vanadium is toxic and that vanadium-containing implants are problematic.^17-20 It has been shown that although Ti6Al4V implants are considered highly resistant to corrosion, they will slowly and continuously corrode in a physiologic environment and release titanium, aluminum, and vanadium ions, both systemically and into the peri-implant space.¹¹ To address these problems with vanadium, vanadium-free titanium alloys such as Ti6Al7Nb have specifically been developed for medical use to address the problems caused by vanadium. Ti6Al7Nb contains 7% niobium rather than vanadium and appears to have some improved qualities in surgical implants.¹⁷

There is still a great deal of uncertainty around metal implant allergy. Allergy to metal implants can be difficult to diagnose for several reasons. Some metals are not conducive to patch testing because of their low bioavailability. Additionally, we lack validated and standardized patch test formulas for metals that can be diagnosed by patch testing. Furthermore, there is uncertainty about what to do after allergy to a metal implant is diagnosed; in some cases (eg, with more extensive procedures such as total joint replacements), removal or replacement of the implant may be associated with increased risk of further complications.^6,21

Conclusion

We suggest that manufacturers consider vanadium-free alloys such as Ti7Al6Nb, which contains niobium instead of vanadium, in their surgical implants,²² and if surgeons have a choice, they should consider using titanium implants with niobium rather than vanadium.¹⁰ We suggest that clinicians consider vanadium allergy in patients with Ti6Al4V surgical implants and signs of a hypersensitivity reaction, and include vanadium trichloride 1% when patch testing.

Acknowledgment

The authors would like to thank Nicholas R. Krasnow, PhD (Tucson, Arizona), for his invaluable help coordinating, performing, and interpreting the metal analyses.

Washington – Help is finally at hand for the subgroup of patients who have severe refractory vasovagal syncope that recurs frequently and unpredictably, and is associated with a strong cardioinhibitory response on tilt table testing, Gonzalo Baron-Esquivias, MD, said at the annual meeting of the American College of Cardiology.

Results of the randomized, multicenter, double-blind, crossover, placebo-controlled SPAIN trial showed that implantation of a permanent pacemaker programmed to a closed loop stimulation (DDD-CLS) algorithm resulted in an 89% decrease in the risk of syncopal recurrences compared with sham DDI pacing, reported Dr. Baron-Esquivias, chief of clinical cardiology at Virgen del Rocio University Hospital in Seville, Spain.

Bruce Jancin/Frontline Medical News

[email protected]

Washington – Help is finally at hand for the subgroup of patients who have severe refractory vasovagal syncope that recurs frequently and unpredictably, and is associated with a strong cardioinhibitory response on tilt table testing, Gonzalo Baron-Esquivias, MD, said at the annual meeting of the American College of Cardiology.

Results of the randomized, multicenter, double-blind, crossover, placebo-controlled SPAIN trial showed that implantation of a permanent pacemaker programmed to a closed loop stimulation (DDD-CLS) algorithm resulted in an 89% decrease in the risk of syncopal recurrences compared with sham DDI pacing, reported Dr. Baron-Esquivias, chief of clinical cardiology at Virgen del Rocio University Hospital in Seville, Spain.

Bruce Jancin/Frontline Medical News

[email protected]

Washington – Help is finally at hand for the subgroup of patients who have severe refractory vasovagal syncope that recurs frequently and unpredictably, and is associated with a strong cardioinhibitory response on tilt table testing, Gonzalo Baron-Esquivias, MD, said at the annual meeting of the American College of Cardiology.

Results of the randomized, multicenter, double-blind, crossover, placebo-controlled SPAIN trial showed that implantation of a permanent pacemaker programmed to a closed loop stimulation (DDD-CLS) algorithm resulted in an 89% decrease in the risk of syncopal recurrences compared with sham DDI pacing, reported Dr. Baron-Esquivias, chief of clinical cardiology at Virgen del Rocio University Hospital in Seville, Spain.

Bruce Jancin/Frontline Medical News

[email protected]

Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.

An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.

juststock/Thinkstock

Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.

An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.

juststock/Thinkstock

Levothyroxine provided no benefits in older patients with subclinical hypothyroidism in the first large randomized clinical trial of the treatment for this indication, which was presented at the annual meeting of the Endocrine Society.

An estimated 8%-18% of people aged 65 and older have subclinical hypothyroidism, which is defined as an elevated serum thyrotropin level and a serum free-thyroxine level within the reference range. The condition is considered to be a possible contributor to many problems affecting numerous physiologic systems including the vascular tree, the heart, the brain, skeletal muscle, and bone, said David J. Stott, MD, of the academic section of geriatric medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow.

juststock/Thinkstock

ORLANDO – Incidence of thyroid cancer increased by an average of 3% annually from 1974-2013, with incidence-based mortality increasing by 1.1% annually from 1994 to 2013, according to a study conducted by the National Cancer Institute.

In a study of 77,726 patients diagnosed with thyroid cancer between 1974 and 2013, incidence rates increased from 4.56 per 100,000 person-years during 1974-1977 to 14.42 per 100,000 person-years during 2010-2013, according to Hyeyeun Lim, PhD, a postdoctoral fellow at National Cancer Institute, and colleagues (JAMA. 2017;317[13]:1338-48).

A majority of patients in the sample were female (75%) and white (82%); average age was 48 years.

A notable trend was the increase in papillary thyroid cancer (PTC). PTC was the most common thyroid cancer at 83.6% of diagnoses, followed by follicular, medullary, anaplastic, and other at 10.8%, 2.2%, 1.3%, and 2.1%, respectively. PTC was associated with the highest annual percent change (4.4%) and the only positive incidence-based mortality annual percent change (1.7%) among all histologic types, according to the researchers.

Regional and distant tumors accounted for 53.2% and 29% of deaths, respectively, compared to 13.5% for local tumors.

Dr. Lim and colleagues interpret the increase in incidence to contradict a common idea among researchers that attributes rising rates to new methods of detection such as ultrasound imaging and fine-needle aspiration biopsies.

“Such changes could account for the rapid increases in the incidence rates for localized and small PTCs that have been previously observed,” the researchers reported. “However, the significant, albeit less-rapid increase in advanced-stage and larger PTC incidence rates and increasing thyroid cancer mortality rates among patients diagnosed with advanced-stage PTC is not consistent with the notion that over-diagnosis is solely responsible for the changing trends in PTC incidence.”

While the researchers reported increased mortality rates among all PTC demographics, statistical significance was found solely in patients with distant disease (annual percentage changes, 2.9% [95% confidence interval, 1.1%-4.7%]), stage IV disease (APC, 12.9%[95%CI, 7.2%-19.0%]), or both, according to researchers.

Researchers speculate increased rates of obesity, childhood ionizing radiation exposure, and increased exposure to pesticides may be possible sources for increased rates of PTC, however Dr. Lim and peers assert further research must be conducted.

Based on these findings, researchers suggest “renewed focus on aggressive transdisciplinary management that includes surgery, adjuvant radioactive iodine, and, when indicated for the 5%-10% of patients who develop progressive disease, systemic therapy,” for patients with advanced-stage PTC.

Due to the nature of the study, researchers were limited to speculating potential reasons for increase in thyroid cancer incidence. Information of tumor size and stage was limited to the years when this information began to be recorded, after the initial years included in the study.

[email protected]

On Twitter @EAZTweets

ORLANDO – Incidence of thyroid cancer increased by an average of 3% annually from 1974-2013, with incidence-based mortality increasing by 1.1% annually from 1994 to 2013, according to a study conducted by the National Cancer Institute.

In a study of 77,726 patients diagnosed with thyroid cancer between 1974 and 2013, incidence rates increased from 4.56 per 100,000 person-years during 1974-1977 to 14.42 per 100,000 person-years during 2010-2013, according to Hyeyeun Lim, PhD, a postdoctoral fellow at National Cancer Institute, and colleagues (JAMA. 2017;317[13]:1338-48).

A majority of patients in the sample were female (75%) and white (82%); average age was 48 years.

A notable trend was the increase in papillary thyroid cancer (PTC). PTC was the most common thyroid cancer at 83.6% of diagnoses, followed by follicular, medullary, anaplastic, and other at 10.8%, 2.2%, 1.3%, and 2.1%, respectively. PTC was associated with the highest annual percent change (4.4%) and the only positive incidence-based mortality annual percent change (1.7%) among all histologic types, according to the researchers.

Regional and distant tumors accounted for 53.2% and 29% of deaths, respectively, compared to 13.5% for local tumors.

Dr. Lim and colleagues interpret the increase in incidence to contradict a common idea among researchers that attributes rising rates to new methods of detection such as ultrasound imaging and fine-needle aspiration biopsies.

“Such changes could account for the rapid increases in the incidence rates for localized and small PTCs that have been previously observed,” the researchers reported. “However, the significant, albeit less-rapid increase in advanced-stage and larger PTC incidence rates and increasing thyroid cancer mortality rates among patients diagnosed with advanced-stage PTC is not consistent with the notion that over-diagnosis is solely responsible for the changing trends in PTC incidence.”

While the researchers reported increased mortality rates among all PTC demographics, statistical significance was found solely in patients with distant disease (annual percentage changes, 2.9% [95% confidence interval, 1.1%-4.7%]), stage IV disease (APC, 12.9%[95%CI, 7.2%-19.0%]), or both, according to researchers.

Researchers speculate increased rates of obesity, childhood ionizing radiation exposure, and increased exposure to pesticides may be possible sources for increased rates of PTC, however Dr. Lim and peers assert further research must be conducted.

Based on these findings, researchers suggest “renewed focus on aggressive transdisciplinary management that includes surgery, adjuvant radioactive iodine, and, when indicated for the 5%-10% of patients who develop progressive disease, systemic therapy,” for patients with advanced-stage PTC.

Due to the nature of the study, researchers were limited to speculating potential reasons for increase in thyroid cancer incidence. Information of tumor size and stage was limited to the years when this information began to be recorded, after the initial years included in the study.

[email protected]

On Twitter @EAZTweets

ORLANDO – Incidence of thyroid cancer increased by an average of 3% annually from 1974-2013, with incidence-based mortality increasing by 1.1% annually from 1994 to 2013, according to a study conducted by the National Cancer Institute.

In a study of 77,726 patients diagnosed with thyroid cancer between 1974 and 2013, incidence rates increased from 4.56 per 100,000 person-years during 1974-1977 to 14.42 per 100,000 person-years during 2010-2013, according to Hyeyeun Lim, PhD, a postdoctoral fellow at National Cancer Institute, and colleagues (JAMA. 2017;317[13]:1338-48).

A majority of patients in the sample were female (75%) and white (82%); average age was 48 years.

A notable trend was the increase in papillary thyroid cancer (PTC). PTC was the most common thyroid cancer at 83.6% of diagnoses, followed by follicular, medullary, anaplastic, and other at 10.8%, 2.2%, 1.3%, and 2.1%, respectively. PTC was associated with the highest annual percent change (4.4%) and the only positive incidence-based mortality annual percent change (1.7%) among all histologic types, according to the researchers.

Regional and distant tumors accounted for 53.2% and 29% of deaths, respectively, compared to 13.5% for local tumors.

Dr. Lim and colleagues interpret the increase in incidence to contradict a common idea among researchers that attributes rising rates to new methods of detection such as ultrasound imaging and fine-needle aspiration biopsies.

“Such changes could account for the rapid increases in the incidence rates for localized and small PTCs that have been previously observed,” the researchers reported. “However, the significant, albeit less-rapid increase in advanced-stage and larger PTC incidence rates and increasing thyroid cancer mortality rates among patients diagnosed with advanced-stage PTC is not consistent with the notion that over-diagnosis is solely responsible for the changing trends in PTC incidence.”

While the researchers reported increased mortality rates among all PTC demographics, statistical significance was found solely in patients with distant disease (annual percentage changes, 2.9% [95% confidence interval, 1.1%-4.7%]), stage IV disease (APC, 12.9%[95%CI, 7.2%-19.0%]), or both, according to researchers.

Researchers speculate increased rates of obesity, childhood ionizing radiation exposure, and increased exposure to pesticides may be possible sources for increased rates of PTC, however Dr. Lim and peers assert further research must be conducted.

Based on these findings, researchers suggest “renewed focus on aggressive transdisciplinary management that includes surgery, adjuvant radioactive iodine, and, when indicated for the 5%-10% of patients who develop progressive disease, systemic therapy,” for patients with advanced-stage PTC.

Due to the nature of the study, researchers were limited to speculating potential reasons for increase in thyroid cancer incidence. Information of tumor size and stage was limited to the years when this information began to be recorded, after the initial years included in the study.

[email protected]

On Twitter @EAZTweets

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

Onychomycosis is a common progressive fungal infection of the nail bed, matrix, or plate leading to destruction and deformity of the toenails and fingernails.^1,2 It represents up to 50% of all nail disorders^1,3 with a notable increasing prevalence in the United States.^4-6

Latinos represent the largest ethnic minority group in the United States,⁷ which is growing rapidly through immigration, particularly in the southern United States. Prevalence data are limited. An incidence of 9.3% secondary to dermatophytes was recorded in a dermatology clinic setting (N=2000).⁸ Onychomycosis was reported in 31.9% of a group of Latino immigrants in North Carolina (N=518), with higher prevalence in poultry workers, possibly due to the work environment.⁹

Efinaconazole solution 10% was shown to be well tolerated and more effective than a vehicle in a phase 2 study in Mexico.¹⁰ Two identical phase 3 studies of 1655 participants assessed the safety and efficacy of efinaconazole solution 10% in the treatment of onychomycosis.¹¹ This post hoc analysis compares the data for Latino versus non-Latino populations.

Methods

We evaluated the results of 2 multicenter, randomized, double-blind, vehicle-controlled studies that included a total of 1655 participants with mild to moderate toenail onychomycosis (20%–50% clinical involvement). Participants were randomized to efinaconazole solu-tion 10% or vehicle once daily (3:1) for 48 weeks with a 4-week posttreatment follow-up period.¹¹

Our post hoc analysis included 270 Latino patients, defined as an individual of Cuban, Mexican, Puerto Rican, or South or Central American origin or other Latino culture, regardless of race. In addition, data were compared to the 1380 non-Latino patients in the 2 studies. Patients who were randomized in error and never received treatment were excluded from the intention-to-treat analysis.

Efficacy Evaluation

The primary efficacy end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Secondary end points included mycologic cure, complete/almost complete cure (≤5% clinical involvement of target toenail, mycologic cure), and treatment success (≤10% clinical involvement of target toenail) at week 52.

Safety Evaluation

Safety assessments included monitoring and recording of adverse events (AEs) at every postbaseline study visit through week 52. All AEs were classified using the Medical Dictionary for Regulatory Activities (version 12.1). Treatment-emergent AEs (ie, events that began after the first application of study drug) that occurred during the study were summarized for each treatment group by the number of patients reporting each event, as well as by system organ class, preferred term, severity, seriousness, and relationship to the study drug.

Results

A total of 270 Latino participants with toenail onychomycosis (efinaconazole solution 10%, n=193; vehicle, n=77) were included in our study. The mean age of participants at baseline was 45.9 years. They were predominantly male (69.6%) and white Latinos (91.1%). The mean area of target toenail involvement was 36.6%, and the mean number of affected nontarget toenails was 2.5. Latino participants tended to be younger than non-Latino participants (45.9 vs 52.6 years), with a higher proportion of females (30.4% vs 21.3%). Disease severity was similar in both populations. Diabetes was reported in 7.0% and 6.7% of Latino and non-Latino participants, respectively, and mean weight was 83.6 and 86.6 kg, respectively.

Primary Efficacy End Points (Observed Case [OC])

At week 52, 25.6% of Latino participants in the efinaconazole group achieved complete cure versus 0% in the vehicle group (P<.001)(Figure 1). The efficacy of efinaconazole was statistically superior in Latino participants versus non-Latino participants (17.2% [P=.012]). The net effect (calculated by active treatment minus vehicle) for Latino participants also was superior to non-Latino participants (25.6% vs 11.6%).

Secondary Efficacy End Points (OC)

At week 52, 61.5% of Latino participants in the efina-conazole group achieved mycologic cure versus 15.3% in the vehicle group (P<.001)(Figure 2). The net effect for Latino participants was superior to non-Latino participants (46.2% vs 38.5%). More Latino participants in the efinaconazole group compared to vehicle group achieved complete/almost complete cure (32.7% vs 1.7%) or treatment success (49.4% vs 5.1%)(all P<.001)(Figure 3). Although there was no significant difference between the 2 groups for secondary efficacy end points, the net effect of efinaconazole was greater for all end points.

Safety

Adverse event rates were higher in the efinaconazole group than the vehicle group (65.3% vs 54.4%) and were similar in both populations; they were generally mild (61.8% vs 54.5%) or moderate (35.3% vs 45.5%) in severity, not related to study medication (96.8% vs 98.0%), and resolved without sequelae. Only 3 Latino participants (1.6%) discontinued efinaconazole treatment compared to 29 (2.8%) in the non-Latino population.

Comment

With the continued growth of the Latino population in the United States and likely higher prevalence of onychomycosis,⁹ this post hoc analysis provides important insights into treatment of onychomycosis in this patient population.

Efinaconazole solution 10% was significantly more effective than vehicle in the Latino population (P<.001) and also appeared significantly more effective than the non-Latino population across the 2 phase 3 studies (P=.012). Interestingly, complete cure rates (25.6%) were identical to those reported in the phase 2 study of Mexican patients treated with efinaconazole for 36 weeks.¹⁰ Specific data with other topical therapies, such as tavaborole, in Latino patients are not available. One phase 3 study of tavaborole for onychomycosis included 89 Mexican patients (15% of the total study population), but complete cure rates for the overall active treatment group were higher in a second phase 3 study (6.5% vs 9.1%) that did not include participants outside the United States or Canada.¹²

It is not clear why phase 3 efficacy results with efinaconazole appear better in the Latino population. There are a number of predisposing factors for onychomycosis that are important treatment considerations in Latinos. Obesity is an important factor in the development of onychomycosis,¹³ with more than 42% of Latino adults in the United States reportedly obese compared to 32.6% of non-Latino adults.¹⁴ Obese patients reportedly have shown a poorer response to efinaconazole treatment¹⁵; however, in our analysis, the mean weight of the 2 subpopulations was similar at baseline. Diabetes also is associated with an increased risk for onychomycosis^16,17 and may be a more important issue in Latinos perhaps due to differences in health care access, social and cultural factors, and/or genetics, as well as the greater incidence of obesity. Prior reports suggest the efficacy of efinaconazole is not substantially influenced by the presence of diabetes,¹⁸ and in our 2 subpopulations, baseline incidence of coexisting diabetes was similar. These factors are unlikely to account for the better treatment success seen in our analysis. Efinaconazole has been reported to be more effective in females,¹⁹ though the reasons are less clear. The higher proportion of female Latinos (30.4% vs 21.3%) in our study may have had an impact on the results reported, though this baseline characteristic cannot be considered in isolation.

When considering the net effect (active minus vehicle), the apparent benefits of efinaconazole in Latino patients with onychomycosis were more marked. Vehicle complete cure rates at week 52 were 0% compared with 5.6% of non-Latino participants. Vehicle cure rates in randomized controlled trials of toenail onychomycosis are relatively low and appear to be independent of the study characteristics.²⁰ Vehicle cure rates of 2 topical treatments—efinaconazole and tavaborole—reported in their 2 respective phase 3 studies were 3.3% and 5.5% for efinaconzole¹¹ and 0.5% and 1.5% for tavaborole.¹² It has been suggested that the higher results seen with the efinaconazole vehicle relate to the formulation, though there is no reason to expect it to perform differently in a Latino population. It also has been suggested that baseline disease severity might impact vehicle treatment outcome.²⁰ In our analysis, the percentage affected nail at baseline was higher in the Latino participants treated with vehicle (38.9% vs 36.2%).

Although the overall level of AEs was similar in Latino versus non-Latino participants treated with efinaconazole, events were generally milder in the Latino subpopulation and fewer participants discontinued because of AEs.

Our study had a number of limitations. A study period of 52 weeks may be too brief to evaluate clinical cure in onychomycosis, as continued improvement could occur with either longer treatment or follow-up. Also, the pivotal studies were not set up to specifically study Latino participants; the demographics and study disposition may not be representative of the general Latino population.

Conclusion

Once-daily treatment with efinaconazole solution 10% may provide a useful topical option in the treatment of Latino patients with toenail onychomycosis.

Acknowledgment

The authors would like to thank Brian Bulley, MSc (Konic Limited, West Sussex, United Kingdom), for medical writing support. Valeant Pharmaceuticals North America LLC funded Konic Limited’s activities pertaining to this manuscript. Dr. Cook-Bolden did not receive funding or any form of compensation for authorship of this publication.

In many parts of the country, spring is finally emerging from the long, hard, cold winter. In almost every culture, spring is associated with rebirth, the return of longer daylight hours, growth, and new life. Like seeds planted in the fall, many of the ideas we at Federal Practitioner sowed in 2016 are now blossoming—our new Historic Profiles and Mental Health Care Practice columns, among others. Just as many of us are engaging in spring cleaning in our homes and yards and opening windows to let in the warmth and the breezes, we at the journal are making room for inspiration and illumination—yours.

Our internal reorganization has enabled us to focus on what we enjoy most—publishing your work. We invite each of you to consider submitting a manuscript and encouraging your colleagues to do so. Almost every health care professional at some time in his or her career has thought of a study to write, read an article they wished they had written, or reviewed a topic they thought suitable for publication. Well, it is time to dust off those ideas and pull them out of the drawer or computer file, just like getting out the warm weather clothing.

In order to reflect the positive trend in federal health care toward multi- and interdisciplinary teams and practice, we welcome submissions from all our clinical constituents, including physicians, surgeons, chaplains, nurses, clinical pharmacists, advanced practice nurses, psychologists, physician assistants, administrators, allied health professionals, and any and all that my old brain cannot recall.

There is nothing like the feeling of seeing your work published in print or on the Internet for the first time in an esteemed journal. If you are a teacher or mentor, think about the gift of inviting a trainee or junior colleague to coauthor an article. This collaboration can be a wonderful shared creative endeavor for educators and their students.

If you have a good idea but are concerned that your writing may be too rough, we invite you to take a leap of faith. Although as a peer-reviewed journal we cannot guarantee acceptance of any manuscript, we can assure you that our editorial staff has smoothed more than a few bumps in our authors’ literary endeavors.

Federal Practitioner is a peer-reviewed journal that has a wide audience among federal health care professionals in the DoD, VA, and PHS. We at the journal are working to become indexed in PubMed, which will provide potential authors with an even wider and more prestigious exposure for their work. We invite you to visit our website and review this print journal to get an idea—if you don’t already have one—of the types of articles we publish. To jump-start your motivation, here is a brief description of the many types of articles we accept.

Feature Articles

Feature articles may be original research or comprehensive summaries of a clinically related topic. The possibilities are as endless as federal practice and could cover medications, other types of interventions (including psychosocial treatments), and reviews of diagnoses.

Original Research

We welcome empirical studies of completed research both biomedical and biobehavioral. More experienced and senior researchers might consider that publication in Federal Practitioner potentially can demonstrate their commitment to conducting research that benefits the members of the armed forces, public services, and veterans, to government funding agencies, increasingly a requirement for grants from those institutions. And for junior or new researchers, we offer a new option to publish pilot studies for research that is just getting launched or is on a smaller scale.

Case Reports

What health care professional has not had a case so memorable that he or she cannot forget it, or a patient encounter that made a lasting impression, or one in which they gained valuable medical knowledge or human wisdom? Ever thought of writing it up for your peers to learn from as well? Submit a case to Federal Practitioner and share your clinical pearls with your colleagues. The authoring process also gives you a chance to review the latest clinical literature on a diagnosis or treatment you wanted to know more about.

Program Profiles

This section of the journal reflects the unparalleled scope and resources of federal health care. Whether it is a national initiative or a local experiment, we want to know and let others read about the beneficial work that you are doing to care for service members, veterans, and the public. Submissions can be of innovative clinical or research projects or programs.

Guest Editorials

While usually members of the Editorial Advisory Association author guest editorials, we are pleased to consider high-quality, thought provoking editorials on themes of health care policy, organization, care delivery, ethics, and professionalism, among others.

Most of us have made the painful adjustment to daylight savings time. Use those extra hours of daylight to stimulate your creative brain. If writing a manuscript does not fit in to your busy schedule right now, think about becoming a peer reviewer or even a member of the Editorial Advisory Association. And last but not least, we are a friendly and open editorial team that is willing to entertain an imaginative suggestion for a manuscript that is novel and vital just like spring.

The Federal Practitioner submission guidelines, accessed at http://www.fedprac.com, include the journal’s style and format. If you need more information or have questions about submitting a manuscript to the journal, e-mail me at [email protected], Editor Reid Paul at [email protected],or Managing Editor Joyce Brody at [email protected].

In many parts of the country, spring is finally emerging from the long, hard, cold winter. In almost every culture, spring is associated with rebirth, the return of longer daylight hours, growth, and new life. Like seeds planted in the fall, many of the ideas we at Federal Practitioner sowed in 2016 are now blossoming—our new Historic Profiles and Mental Health Care Practice columns, among others. Just as many of us are engaging in spring cleaning in our homes and yards and opening windows to let in the warmth and the breezes, we at the journal are making room for inspiration and illumination—yours.

Our internal reorganization has enabled us to focus on what we enjoy most—publishing your work. We invite each of you to consider submitting a manuscript and encouraging your colleagues to do so. Almost every health care professional at some time in his or her career has thought of a study to write, read an article they wished they had written, or reviewed a topic they thought suitable for publication. Well, it is time to dust off those ideas and pull them out of the drawer or computer file, just like getting out the warm weather clothing.

In order to reflect the positive trend in federal health care toward multi- and interdisciplinary teams and practice, we welcome submissions from all our clinical constituents, including physicians, surgeons, chaplains, nurses, clinical pharmacists, advanced practice nurses, psychologists, physician assistants, administrators, allied health professionals, and any and all that my old brain cannot recall.

There is nothing like the feeling of seeing your work published in print or on the Internet for the first time in an esteemed journal. If you are a teacher or mentor, think about the gift of inviting a trainee or junior colleague to coauthor an article. This collaboration can be a wonderful shared creative endeavor for educators and their students.

If you have a good idea but are concerned that your writing may be too rough, we invite you to take a leap of faith. Although as a peer-reviewed journal we cannot guarantee acceptance of any manuscript, we can assure you that our editorial staff has smoothed more than a few bumps in our authors’ literary endeavors.

Federal Practitioner is a peer-reviewed journal that has a wide audience among federal health care professionals in the DoD, VA, and PHS. We at the journal are working to become indexed in PubMed, which will provide potential authors with an even wider and more prestigious exposure for their work. We invite you to visit our website and review this print journal to get an idea—if you don’t already have one—of the types of articles we publish. To jump-start your motivation, here is a brief description of the many types of articles we accept.

Feature Articles

Feature articles may be original research or comprehensive summaries of a clinically related topic. The possibilities are as endless as federal practice and could cover medications, other types of interventions (including psychosocial treatments), and reviews of diagnoses.

Original Research

We welcome empirical studies of completed research both biomedical and biobehavioral. More experienced and senior researchers might consider that publication in Federal Practitioner potentially can demonstrate their commitment to conducting research that benefits the members of the armed forces, public services, and veterans, to government funding agencies, increasingly a requirement for grants from those institutions. And for junior or new researchers, we offer a new option to publish pilot studies for research that is just getting launched or is on a smaller scale.

Case Reports

What health care professional has not had a case so memorable that he or she cannot forget it, or a patient encounter that made a lasting impression, or one in which they gained valuable medical knowledge or human wisdom? Ever thought of writing it up for your peers to learn from as well? Submit a case to Federal Practitioner and share your clinical pearls with your colleagues. The authoring process also gives you a chance to review the latest clinical literature on a diagnosis or treatment you wanted to know more about.

Program Profiles

This section of the journal reflects the unparalleled scope and resources of federal health care. Whether it is a national initiative or a local experiment, we want to know and let others read about the beneficial work that you are doing to care for service members, veterans, and the public. Submissions can be of innovative clinical or research projects or programs.

Guest Editorials

While usually members of the Editorial Advisory Association author guest editorials, we are pleased to consider high-quality, thought provoking editorials on themes of health care policy, organization, care delivery, ethics, and professionalism, among others.

Most of us have made the painful adjustment to daylight savings time. Use those extra hours of daylight to stimulate your creative brain. If writing a manuscript does not fit in to your busy schedule right now, think about becoming a peer reviewer or even a member of the Editorial Advisory Association. And last but not least, we are a friendly and open editorial team that is willing to entertain an imaginative suggestion for a manuscript that is novel and vital just like spring.

The Federal Practitioner submission guidelines, accessed at http://www.fedprac.com, include the journal’s style and format. If you need more information or have questions about submitting a manuscript to the journal, e-mail me at [email protected], Editor Reid Paul at [email protected],or Managing Editor Joyce Brody at [email protected].

In many parts of the country, spring is finally emerging from the long, hard, cold winter. In almost every culture, spring is associated with rebirth, the return of longer daylight hours, growth, and new life. Like seeds planted in the fall, many of the ideas we at Federal Practitioner sowed in 2016 are now blossoming—our new Historic Profiles and Mental Health Care Practice columns, among others. Just as many of us are engaging in spring cleaning in our homes and yards and opening windows to let in the warmth and the breezes, we at the journal are making room for inspiration and illumination—yours.

Our internal reorganization has enabled us to focus on what we enjoy most—publishing your work. We invite each of you to consider submitting a manuscript and encouraging your colleagues to do so. Almost every health care professional at some time in his or her career has thought of a study to write, read an article they wished they had written, or reviewed a topic they thought suitable for publication. Well, it is time to dust off those ideas and pull them out of the drawer or computer file, just like getting out the warm weather clothing.

In order to reflect the positive trend in federal health care toward multi- and interdisciplinary teams and practice, we welcome submissions from all our clinical constituents, including physicians, surgeons, chaplains, nurses, clinical pharmacists, advanced practice nurses, psychologists, physician assistants, administrators, allied health professionals, and any and all that my old brain cannot recall.

There is nothing like the feeling of seeing your work published in print or on the Internet for the first time in an esteemed journal. If you are a teacher or mentor, think about the gift of inviting a trainee or junior colleague to coauthor an article. This collaboration can be a wonderful shared creative endeavor for educators and their students.

If you have a good idea but are concerned that your writing may be too rough, we invite you to take a leap of faith. Although as a peer-reviewed journal we cannot guarantee acceptance of any manuscript, we can assure you that our editorial staff has smoothed more than a few bumps in our authors’ literary endeavors.

Federal Practitioner is a peer-reviewed journal that has a wide audience among federal health care professionals in the DoD, VA, and PHS. We at the journal are working to become indexed in PubMed, which will provide potential authors with an even wider and more prestigious exposure for their work. We invite you to visit our website and review this print journal to get an idea—if you don’t already have one—of the types of articles we publish. To jump-start your motivation, here is a brief description of the many types of articles we accept.

Feature Articles

Feature articles may be original research or comprehensive summaries of a clinically related topic. The possibilities are as endless as federal practice and could cover medications, other types of interventions (including psychosocial treatments), and reviews of diagnoses.

Original Research

We welcome empirical studies of completed research both biomedical and biobehavioral. More experienced and senior researchers might consider that publication in Federal Practitioner potentially can demonstrate their commitment to conducting research that benefits the members of the armed forces, public services, and veterans, to government funding agencies, increasingly a requirement for grants from those institutions. And for junior or new researchers, we offer a new option to publish pilot studies for research that is just getting launched or is on a smaller scale.

Case Reports

What health care professional has not had a case so memorable that he or she cannot forget it, or a patient encounter that made a lasting impression, or one in which they gained valuable medical knowledge or human wisdom? Ever thought of writing it up for your peers to learn from as well? Submit a case to Federal Practitioner and share your clinical pearls with your colleagues. The authoring process also gives you a chance to review the latest clinical literature on a diagnosis or treatment you wanted to know more about.

Program Profiles

This section of the journal reflects the unparalleled scope and resources of federal health care. Whether it is a national initiative or a local experiment, we want to know and let others read about the beneficial work that you are doing to care for service members, veterans, and the public. Submissions can be of innovative clinical or research projects or programs.

Guest Editorials

While usually members of the Editorial Advisory Association author guest editorials, we are pleased to consider high-quality, thought provoking editorials on themes of health care policy, organization, care delivery, ethics, and professionalism, among others.

Most of us have made the painful adjustment to daylight savings time. Use those extra hours of daylight to stimulate your creative brain. If writing a manuscript does not fit in to your busy schedule right now, think about becoming a peer reviewer or even a member of the Editorial Advisory Association. And last but not least, we are a friendly and open editorial team that is willing to entertain an imaginative suggestion for a manuscript that is novel and vital just like spring.

The Federal Practitioner submission guidelines, accessed at http://www.fedprac.com, include the journal’s style and format. If you need more information or have questions about submitting a manuscript to the journal, e-mail me at [email protected], Editor Reid Paul at [email protected],or Managing Editor Joyce Brody at [email protected].

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Aktipak

Cutanea Life Sciences, Inc, launches Aktipak (erythromycin 3% and benzoyl peroxide 5%) Gel, a prescription combination therapy indicated for acne vulgaris. Aktipak is packaged in a pocket-sized, dual-chamber pouch that contains erythromycin and benzoyl peroxide in separate chambers to enable convenient on-the-go use. Immediately prior to use, the patient cuts or twists open the pouch, squeezes the 2 gels into the palm of the hand, mixes the gels together, and applies the mix to the area affected by acne. Aktipak has an 18-month shelf life and does not require refrigeration. Results can be seen within 8 weeks. For more information, visit www.aktipak.com.

Glytone Acne BPO Clearing Cleanser

Pierre Fabre Group introduces the Glytone Acne BPO Clearing Cleanser (4.5% encapsulated benzoyl peroxide [BPO]) with time-released technology to control the delivery of BPO and enhance penetration. The targeted delivery system adheres to the skin and penetrates the lipid layer while releasing the encapsulated BPO once warmed by the skin, providing optimal efficacy to inhibit the growth of acne-causing bacteria with minimal irritation. Glytone Acne BPO Clearing Cleanser is dispensed by physicians and can be used with other products in the Glytone acne product line for optimal results. For more information, visit www.glytone-usa.com.

Juvéderm Vollure XC

Allergan announces US Food and Drug Administration approval of Juvéderm Vollure XC for correction of moderate to severe facial wrinkles and folds such as the nasolabial folds in adults older than 21 years. It utilizes VYCROSS technology, which blends different weights of hyaluronic acid, contributing to the gel’s duration. Long-lasting results have been demonstrated up to 18 months. For more information, visit www.juvederm.com.

Neutrogena Light Therapy Acne Mask

Johnson & Johnson Consumer Inc presents the Neutrogena Light Therapy Acne Mask, an LED device utilizing red and blue light to treat acne at home. The mask contains 12 blue LED bulbs that kill Propionibacterium acnes bacteria and 9 red LED bulbs to penetrate deep into the skin to calm inflammation. The mask can be used for 10 minutes each night and shuts off automatically. Results have been seen in 1 week for mild to moderate acne. For more information, visit www.neutrogena.com.

3% Retinol Peel ProSystem

NeoStrata Company, Inc, introduces the 3% Retinol Peel ProSystem featuring Retinol Boosting Complex to exfoliate and improve the appearance of fine lines and winkles, help reduce acne, and improve skin laxity, while promoting a bright, even, and clear complexion. This physician-strength peel is applied in the office but is removed at home after 8 hours or overnight. This peel has demonstrated improvement in acne and skin texture as well as diminished pigmentation. For more information, visit www.neostrata.com.

Siliq

Valeant Pharmaceuticals International, Inc, announces US Food and Drug Administration approval of the Biologics License Application for Siliq (brodalumab) injection. Siliq, an IL-17 inhibitor, is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Siliq has a black box warning for patients with a history of suicidal thoughts or behavior and was approved with a Risk Evaluation and Mitigation Strategy involving a one-time enrollment for physicians and one-time informed consent for patients. Sales and marketing in the United States will begin in the second half of 2017. For more information, visit www.valeant.com.

Thermi

Thermi, an Almirall company, announces “The Art of Thermi” campaign focusing on 2 Thermi devices: ThermiRF and Thermi250. ThermiRF is temperature-controlled radiofrequency technology that uses heat to produce aesthetic outcomes for soft tissue applications. Thermi250 is a high-powered, temperature-controlled radiofrequency system emitting at 470 kHz designed with a user-friendly interface to offer versatility for targeting cellulite. For more information, visit www.thermi.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”