A pared-down version of the 21st Century Cures Act passed the House Nov. 30 by an overwhelming 392-26 vote, setting the stage for a quick Senate vote on the compromise legislation.

H.R. 34 gained more support on the House floor than did a version of the legislation that passed the House in 2015. In order to gain that additional support and ensure Senate approval, funding for key biomedical research efforts – the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative – was reduced from $9.3 billion to $4.8 billion over 10 years. Further, those funds are not guaranteed but will need to be appropriated through the federal budget process.

Alicia Ault/Frontline Medical News

Other provisions include creation of an NIH program to support new researchers; funds to accelerate improved methods for prevention, diagnosis, and treatment of tick-borne diseases; the development of a national neurologic condition surveillance system; and the establishment of a task force on research specific to pregnant and breastfeeding women.

“More women with chronic diseases are becoming pregnant, yet safe and effective medications to manage these ongoing conditions throughout their pregnancy and beyond are needed,” Mary Norton, MD, president of the Society for Maternal-Fetal Medicine, said in a statement. “This legislation is a great first step toward greater collaboration and communication among federal agencies and public stakeholders.”

The 21st Century Cures bill also “takes concrete steps to help women and families suffering from postpartum depression,” Thomas Gellhaus, MD, president of the American College of Obstetricians and Gynecologists, said in a statement. “Postpartum depression is one of the most common medical complications following pregnancy. ... Cures expands state programs to better identify, treat, and support women and families at risk for or facing postpartum depression.”

The bill provides $500 million to the Food and Drug Administration to help the agency speed up the drug approval process, focusing on identifying biomarkers and developing targeted drugs for rare diseases. It also reauthorizes the pediatric rare disease priority review voucher program; requires drug companies to have a publicly accessible compassionate use policy for drugs treating serious or life-threatening conditions; and provides flexibility to get new antimicrobial drugs to market quickly.

Changes in the drug approval process were contentious during debate on the House floor.

“In its attempt to speed up the drug and device approval process, this legislation neglects the very people whom clinical trials are meant to help, that is, the patients,” Rep. Rosa DeLauro (D-Conn.) said. “Rather than protect those who rely on the health care system, it reduces the already weak regulation on medical devices, allows drugs with only limited evidence of the drug’s safety and efficacy, and rushes the use of new and unproven antibiotics.”

Other legislators expressed disappointment at the bill’s mental health care provisions. Rep. Joseph Kennedy III (D-Mass.) said that his “real concerns with the legislation lie with the mental health reform proposals, which don’t go nearly far enough. Mental health parity is already the law, thanks to the Mental Health Parity and Addiction Equity Act and the Affordable Care Act; but each study we read, Mr. Speaker, and each story we hear proves that insurance companies are skirting those rules.

“We need enforcement and transparency today,” Rep. Kennedy continued. “We need random audits before there have been violations, not after. We need insurers to publicly disclose the rates and reasons for denials in a way that patients and their families can understand, not in away that mental health advocates can’t even obtain. We need to increase Medicaid reimbursements in order to expand access to care, not to reduce them or roll back expansion.”

The pediatric provisions drew mixed reviews from the American Academy of Pediatrics.

“The 21st Century Cures Act includes three new programs that, if funded, would improve infant and child mental health: one that supports behavioral and mental health integration into the pediatric primary care setting, one that increases screening and treatment for maternal depression, and one that enhances infant and early childhood mental health,” AAP President Benard Dreyer, MD, said in a statement. “Of additional note is a provision that incentivizes the certification of health information technology for use by pediatricians, and a provision that ensures children in [psychiatric facilities] receive Medicaid’s early periodic screening, treatment, and diagnosis gold standard of care. Finally, the AAP supports the 21st Century Cures Act’s reauthorization of a bill to prevent underage drinking, which includes a new program to train pediatric health professionals in substance use screening, intervention, and referrals.”

However, Dr. Dreyer noted that more work needs to be done.

“The Family First Prevention Services Act of 2016, a comprehensive, bipartisan effort to improve how the child welfare system serves children and families in adversity, was connected to the 21st Century Cures Act until earlier this week,” he said. “Family First represents more than 2 years of work, and is a pivotal opportunity for a major federal policy shift away from placing children in out-of-home care and toward keeping families together. Removing it from this legislative package could mean losing the chance to pass it at all, an unacceptable and undeserved setback for the nation’s most vulnerable children.”

21st Century Cures also contains health IT-related provisions, mostly aimed at improving the interoperability of electronic health records. It also reduces the documentation burden on providers and establishes the authority for the HHS Office of Inspector General to penalize those engaged in information blocking between EHRs.

The bill also increases the transparency around Medicare local coverage decisions and exempts certain transfers of value from reporting requirements related to continuing education. It sets reimbursement for Medicare Part B drugs infused through durable medical equipment at 106% of average sales price.

Sen. Lamar Alexander, chairman of the Health, Education, Labor and Pensions Committee, said that a vote in that chamber could happen as early as Dec. 5. Upon House passage, President Obama signaled his intention to sign the bill, according to a statement from the White House Press Secretary.

[email protected]

A pared-down version of the 21st Century Cures Act passed the House Nov. 30 by an overwhelming 392-26 vote, setting the stage for a quick Senate vote on the compromise legislation.

H.R. 34 gained more support on the House floor than did a version of the legislation that passed the House in 2015. In order to gain that additional support and ensure Senate approval, funding for key biomedical research efforts – the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative – was reduced from $9.3 billion to $4.8 billion over 10 years. Further, those funds are not guaranteed but will need to be appropriated through the federal budget process.

Alicia Ault/Frontline Medical News

Other provisions include creation of an NIH program to support new researchers; funds to accelerate improved methods for prevention, diagnosis, and treatment of tick-borne diseases; the development of a national neurologic condition surveillance system; and the establishment of a task force on research specific to pregnant and breastfeeding women.

“More women with chronic diseases are becoming pregnant, yet safe and effective medications to manage these ongoing conditions throughout their pregnancy and beyond are needed,” Mary Norton, MD, president of the Society for Maternal-Fetal Medicine, said in a statement. “This legislation is a great first step toward greater collaboration and communication among federal agencies and public stakeholders.”

The 21st Century Cures bill also “takes concrete steps to help women and families suffering from postpartum depression,” Thomas Gellhaus, MD, president of the American College of Obstetricians and Gynecologists, said in a statement. “Postpartum depression is one of the most common medical complications following pregnancy. ... Cures expands state programs to better identify, treat, and support women and families at risk for or facing postpartum depression.”

The bill provides $500 million to the Food and Drug Administration to help the agency speed up the drug approval process, focusing on identifying biomarkers and developing targeted drugs for rare diseases. It also reauthorizes the pediatric rare disease priority review voucher program; requires drug companies to have a publicly accessible compassionate use policy for drugs treating serious or life-threatening conditions; and provides flexibility to get new antimicrobial drugs to market quickly.

Changes in the drug approval process were contentious during debate on the House floor.

“In its attempt to speed up the drug and device approval process, this legislation neglects the very people whom clinical trials are meant to help, that is, the patients,” Rep. Rosa DeLauro (D-Conn.) said. “Rather than protect those who rely on the health care system, it reduces the already weak regulation on medical devices, allows drugs with only limited evidence of the drug’s safety and efficacy, and rushes the use of new and unproven antibiotics.”

Other legislators expressed disappointment at the bill’s mental health care provisions. Rep. Joseph Kennedy III (D-Mass.) said that his “real concerns with the legislation lie with the mental health reform proposals, which don’t go nearly far enough. Mental health parity is already the law, thanks to the Mental Health Parity and Addiction Equity Act and the Affordable Care Act; but each study we read, Mr. Speaker, and each story we hear proves that insurance companies are skirting those rules.

“We need enforcement and transparency today,” Rep. Kennedy continued. “We need random audits before there have been violations, not after. We need insurers to publicly disclose the rates and reasons for denials in a way that patients and their families can understand, not in away that mental health advocates can’t even obtain. We need to increase Medicaid reimbursements in order to expand access to care, not to reduce them or roll back expansion.”

The pediatric provisions drew mixed reviews from the American Academy of Pediatrics.

“The 21st Century Cures Act includes three new programs that, if funded, would improve infant and child mental health: one that supports behavioral and mental health integration into the pediatric primary care setting, one that increases screening and treatment for maternal depression, and one that enhances infant and early childhood mental health,” AAP President Benard Dreyer, MD, said in a statement. “Of additional note is a provision that incentivizes the certification of health information technology for use by pediatricians, and a provision that ensures children in [psychiatric facilities] receive Medicaid’s early periodic screening, treatment, and diagnosis gold standard of care. Finally, the AAP supports the 21st Century Cures Act’s reauthorization of a bill to prevent underage drinking, which includes a new program to train pediatric health professionals in substance use screening, intervention, and referrals.”

However, Dr. Dreyer noted that more work needs to be done.

“The Family First Prevention Services Act of 2016, a comprehensive, bipartisan effort to improve how the child welfare system serves children and families in adversity, was connected to the 21st Century Cures Act until earlier this week,” he said. “Family First represents more than 2 years of work, and is a pivotal opportunity for a major federal policy shift away from placing children in out-of-home care and toward keeping families together. Removing it from this legislative package could mean losing the chance to pass it at all, an unacceptable and undeserved setback for the nation’s most vulnerable children.”

21st Century Cures also contains health IT-related provisions, mostly aimed at improving the interoperability of electronic health records. It also reduces the documentation burden on providers and establishes the authority for the HHS Office of Inspector General to penalize those engaged in information blocking between EHRs.

The bill also increases the transparency around Medicare local coverage decisions and exempts certain transfers of value from reporting requirements related to continuing education. It sets reimbursement for Medicare Part B drugs infused through durable medical equipment at 106% of average sales price.

Sen. Lamar Alexander, chairman of the Health, Education, Labor and Pensions Committee, said that a vote in that chamber could happen as early as Dec. 5. Upon House passage, President Obama signaled his intention to sign the bill, according to a statement from the White House Press Secretary.

[email protected]

A pared-down version of the 21st Century Cures Act passed the House Nov. 30 by an overwhelming 392-26 vote, setting the stage for a quick Senate vote on the compromise legislation.

H.R. 34 gained more support on the House floor than did a version of the legislation that passed the House in 2015. In order to gain that additional support and ensure Senate approval, funding for key biomedical research efforts – the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative – was reduced from $9.3 billion to $4.8 billion over 10 years. Further, those funds are not guaranteed but will need to be appropriated through the federal budget process.

Alicia Ault/Frontline Medical News

Other provisions include creation of an NIH program to support new researchers; funds to accelerate improved methods for prevention, diagnosis, and treatment of tick-borne diseases; the development of a national neurologic condition surveillance system; and the establishment of a task force on research specific to pregnant and breastfeeding women.

“More women with chronic diseases are becoming pregnant, yet safe and effective medications to manage these ongoing conditions throughout their pregnancy and beyond are needed,” Mary Norton, MD, president of the Society for Maternal-Fetal Medicine, said in a statement. “This legislation is a great first step toward greater collaboration and communication among federal agencies and public stakeholders.”

The 21st Century Cures bill also “takes concrete steps to help women and families suffering from postpartum depression,” Thomas Gellhaus, MD, president of the American College of Obstetricians and Gynecologists, said in a statement. “Postpartum depression is one of the most common medical complications following pregnancy. ... Cures expands state programs to better identify, treat, and support women and families at risk for or facing postpartum depression.”

The bill provides $500 million to the Food and Drug Administration to help the agency speed up the drug approval process, focusing on identifying biomarkers and developing targeted drugs for rare diseases. It also reauthorizes the pediatric rare disease priority review voucher program; requires drug companies to have a publicly accessible compassionate use policy for drugs treating serious or life-threatening conditions; and provides flexibility to get new antimicrobial drugs to market quickly.

Changes in the drug approval process were contentious during debate on the House floor.

“In its attempt to speed up the drug and device approval process, this legislation neglects the very people whom clinical trials are meant to help, that is, the patients,” Rep. Rosa DeLauro (D-Conn.) said. “Rather than protect those who rely on the health care system, it reduces the already weak regulation on medical devices, allows drugs with only limited evidence of the drug’s safety and efficacy, and rushes the use of new and unproven antibiotics.”

Other legislators expressed disappointment at the bill’s mental health care provisions. Rep. Joseph Kennedy III (D-Mass.) said that his “real concerns with the legislation lie with the mental health reform proposals, which don’t go nearly far enough. Mental health parity is already the law, thanks to the Mental Health Parity and Addiction Equity Act and the Affordable Care Act; but each study we read, Mr. Speaker, and each story we hear proves that insurance companies are skirting those rules.

“We need enforcement and transparency today,” Rep. Kennedy continued. “We need random audits before there have been violations, not after. We need insurers to publicly disclose the rates and reasons for denials in a way that patients and their families can understand, not in away that mental health advocates can’t even obtain. We need to increase Medicaid reimbursements in order to expand access to care, not to reduce them or roll back expansion.”

The pediatric provisions drew mixed reviews from the American Academy of Pediatrics.

“The 21st Century Cures Act includes three new programs that, if funded, would improve infant and child mental health: one that supports behavioral and mental health integration into the pediatric primary care setting, one that increases screening and treatment for maternal depression, and one that enhances infant and early childhood mental health,” AAP President Benard Dreyer, MD, said in a statement. “Of additional note is a provision that incentivizes the certification of health information technology for use by pediatricians, and a provision that ensures children in [psychiatric facilities] receive Medicaid’s early periodic screening, treatment, and diagnosis gold standard of care. Finally, the AAP supports the 21st Century Cures Act’s reauthorization of a bill to prevent underage drinking, which includes a new program to train pediatric health professionals in substance use screening, intervention, and referrals.”

However, Dr. Dreyer noted that more work needs to be done.

“The Family First Prevention Services Act of 2016, a comprehensive, bipartisan effort to improve how the child welfare system serves children and families in adversity, was connected to the 21st Century Cures Act until earlier this week,” he said. “Family First represents more than 2 years of work, and is a pivotal opportunity for a major federal policy shift away from placing children in out-of-home care and toward keeping families together. Removing it from this legislative package could mean losing the chance to pass it at all, an unacceptable and undeserved setback for the nation’s most vulnerable children.”

21st Century Cures also contains health IT-related provisions, mostly aimed at improving the interoperability of electronic health records. It also reduces the documentation burden on providers and establishes the authority for the HHS Office of Inspector General to penalize those engaged in information blocking between EHRs.

The bill also increases the transparency around Medicare local coverage decisions and exempts certain transfers of value from reporting requirements related to continuing education. It sets reimbursement for Medicare Part B drugs infused through durable medical equipment at 106% of average sales price.

Sen. Lamar Alexander, chairman of the Health, Education, Labor and Pensions Committee, said that a vote in that chamber could happen as early as Dec. 5. Upon House passage, President Obama signaled his intention to sign the bill, according to a statement from the White House Press Secretary.

[email protected]

To the Editor:

We commend the recent report by Smith et al (Cutis. 2016;97:166, 175-176) that described multiple white nodules on the bilateral helical rims of the ears in a 40-year-old man, which was determined to be bilateral auricular tophaceous gout. Furthermore, we appreciate the inclusion of weathering nodules in the differential diagnosis and wish to share our experience with these lesions.

Auricular tophaceous gout and weathering nodules are clinically similar. Weathering nodules may appear as single or multiple, 2 to 3 mm in diameter and 1 to 2 mm in height, white to flesh-colored papules usually found on the helical rim of the ear (Figure 1).¹ We recently described 10 patients with weathering nodules and their associated risk factors.² We observed that the weathering nodules will blanch upon the application of pressure to the adjacent helical rim; a positive “blanch sign” may be used to differentiate weathering nodules from auricular tophaceous gout and other lesions of the ear (Figure 2). Furthermore, patients with weathering nodules typically exhibit a history of sun exposure and often have other cutaneous findings such as actinic keratoses. The pathogenesis of weathering nodules was previously thought to rely solely on actinic damage; however, we reported a pediatric case of weathering nodules that presented following radiotherapy to the ears.²

In summary, weathering nodules should be included in the differential diagnosis of auricular tophaceous gout. In addition, a positive blanch sign may be a useful clinical tool in differentiating weathering nodules from other ear lesions.

To the Editor:

We commend the recent report by Smith et al (Cutis. 2016;97:166, 175-176) that described multiple white nodules on the bilateral helical rims of the ears in a 40-year-old man, which was determined to be bilateral auricular tophaceous gout. Furthermore, we appreciate the inclusion of weathering nodules in the differential diagnosis and wish to share our experience with these lesions.

Auricular tophaceous gout and weathering nodules are clinically similar. Weathering nodules may appear as single or multiple, 2 to 3 mm in diameter and 1 to 2 mm in height, white to flesh-colored papules usually found on the helical rim of the ear (Figure 1).¹ We recently described 10 patients with weathering nodules and their associated risk factors.² We observed that the weathering nodules will blanch upon the application of pressure to the adjacent helical rim; a positive “blanch sign” may be used to differentiate weathering nodules from auricular tophaceous gout and other lesions of the ear (Figure 2). Furthermore, patients with weathering nodules typically exhibit a history of sun exposure and often have other cutaneous findings such as actinic keratoses. The pathogenesis of weathering nodules was previously thought to rely solely on actinic damage; however, we reported a pediatric case of weathering nodules that presented following radiotherapy to the ears.²

In summary, weathering nodules should be included in the differential diagnosis of auricular tophaceous gout. In addition, a positive blanch sign may be a useful clinical tool in differentiating weathering nodules from other ear lesions.

To the Editor:

We commend the recent report by Smith et al (Cutis. 2016;97:166, 175-176) that described multiple white nodules on the bilateral helical rims of the ears in a 40-year-old man, which was determined to be bilateral auricular tophaceous gout. Furthermore, we appreciate the inclusion of weathering nodules in the differential diagnosis and wish to share our experience with these lesions.

Auricular tophaceous gout and weathering nodules are clinically similar. Weathering nodules may appear as single or multiple, 2 to 3 mm in diameter and 1 to 2 mm in height, white to flesh-colored papules usually found on the helical rim of the ear (Figure 1).¹ We recently described 10 patients with weathering nodules and their associated risk factors.² We observed that the weathering nodules will blanch upon the application of pressure to the adjacent helical rim; a positive “blanch sign” may be used to differentiate weathering nodules from auricular tophaceous gout and other lesions of the ear (Figure 2). Furthermore, patients with weathering nodules typically exhibit a history of sun exposure and often have other cutaneous findings such as actinic keratoses. The pathogenesis of weathering nodules was previously thought to rely solely on actinic damage; however, we reported a pediatric case of weathering nodules that presented following radiotherapy to the ears.²

In summary, weathering nodules should be included in the differential diagnosis of auricular tophaceous gout. In addition, a positive blanch sign may be a useful clinical tool in differentiating weathering nodules from other ear lesions.

WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.

The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.

“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.

The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).

Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.

High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.

“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”

Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.

Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.

Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.

There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.

However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.

The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.

There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.

Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.

Dr. Tamirou and her colleagues had no financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.

The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.

“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.

The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).

Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.

High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.

“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”

Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.

Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.

Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.

There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.

However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.

The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.

There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.

Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.

Dr. Tamirou and her colleagues had no financial disclosures.

[email protected]

On Twitter @alz_gal

WASHINGTON – Low-dose pulsed cyclophosphamide doesn’t appear to affect ovarian reserve when used to treat women with systemic lupus erythematosus, according to an analysis of patients’ anti-Mullerian hormone levels.

The protocol – known as the Euro-Lupus regimen – may be the best choice for younger patients with systemic lupus erythematosus (SLE) who wish to preserve their fertility, Farah Tamirou, MD, said at the annual meeting of the American College of Rheumatology.

“I think we can say that the Euro-Lupus regimen can be safely proposed to patients with future pregnancy plans,” said Dr. Tamirou of the University Clinic Saint-Luc, Brussels.

The protocol was first reported in the Euro-Lupus Nephritis Trial, published in 2002. The study randomized 90 lupus patients with proliferative glomerulonephritis to high-dose intravenous cyclophosphamide (six monthly pulses and two quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose regimen (six pulses at a fixed dose of 500 mg), each of which was followed by azathioprine (Arthritis Rheum. 2002;46[8]:2121-31).

Patients actually did better on the low-dose regimen: 16% experienced treatment failure, compared to 20% of those in the high-dose group. Renal remission occurred in 71% of the low-dose group and 54% of the high-dose group.

High-dose cyclophosphamide has proven to be gonadotoxic, but no studies have assessed whether the low-dose regimen may be gonadoprotective, Dr. Tamirou said. Nevertheless, she said there have been no reports of sustained amenorrhea associated with it.

“However, sustained amenorrhea is a poor endpoint for fertility. It doesn’t quantify the full effect of cyclophosphamide on ovarian reserve, especially in young women with more reserve, who may experience cytotoxic damage that is not enough to cause full cessation of ovarian function.”

Anti-Müllerian hormone (AMH) seems to be a better marker of subclinical ovarian damage. AMH is produced by granulosa cells in growing ovarian follicles. The level of AMH is highest in primordial follicles and decreases as the follicles mature. Since it’s only made in these immature ova, AMH is considered to be a fairly accurate measure of ovarian reserve, Dr. Tamirou said. AMH naturally decreases with advancing age, increasing body mass index, pregnancy, and menopause, but it’s not influenced by the menstrual cycle or by any hormonal contraceptive.

Given this utility, Dr. Tamirou and her colleagues used AMH levels to assess cyclophosphamide-induced ovarian damage in 155 patients with SLE. They measured AMH in the frozen sera of patients who had received different cumulative cyclophosphamide doses: up to 3 grams, 3-6 grams, and more than 6 grams. They compared AMH levels at those cumulative dose ranges with AMH levels in patients who had not been treated with cyclophosphamide.

Since the patients were of widely varied ages, Dr. Tamirou and her associates created an age-adjusted slope for normal AMH levels in the nontreated group, which were normalized for 30 years – the mean age of the entire cohort.

There were 101 patients in the nontreated group, and their mean age-adjusted AMH level was 2.8 ng/mL. There were 11 patients in the 3- to 6-gram cyclophosphamide group, and they had a mean AMH of 2.5 ng/mL – not significantly different from the nontreated group. The group of 30 patients who received up to 3 grams of cyclophosphamide had a similar mean age-adjusted AMH level of 3 ng/mL.

However, for 13 patients who received more than 6 grams of cyclophosphamide, the mean age-adjusted AMH level was 1.4 ng/mL, which was significantly lower than any of the other treatment groups.

The investigators conducted several subanalyses to see if there were any clinical characteristics that could have contributed to the AMH level differences. Cumulative cyclophosphamide dose was, as expected, directly related to disease duration. Untreated women and those in the lowest dose group had a mean disease duration of 9 years, while those who took 3-6 grams had a mean duration of 11 years. The disease duration was 15 years among those who received 6 or more grams.

There were no associations with any organ involvement or related immunosuppressive disorders. AMH was not associated with body mass index or the use of hormonal contraception. Nor were there any significant associations with prednisone use or dosage, or disease severity, she added.

Finally, the investigators conducted a subanalysis of 10 patients who had blood drawn before and after entering the Euro-Lupus regimen. None of these women showed any significant change in AMH levels after being on the treatment.

Dr. Tamirou and her colleagues had no financial disclosures.

[email protected]

On Twitter @alz_gal

NEW ORLEANS – The future doesn’t look bright at the moment for use of agents that mimic HDL cholesterol to reverse coronary disease, based on disappointing results of the randomized, phase II MILANO-PILOT trial.

Among 120 patients with recent acute coronary syndrome, a mimetic known as MDCO-216 was no better than placebo at reducing coronary plaque measured by intravascular ultrasound (IVUS), according to data presented at the American Heart Association scientific sessions.

The median reduction in percent atheroma volume, the trial’s primary endpoint, was 0.5% with the mimetic and 0.8% with placebo, reported Stephen J. Nicholls, MD, of the South Australian Health and Medical Research Institute, University of Adelaide (Australia). Findings were similar for secondary outcomes assessing other measures of disease regression.

These data bring to an end a story that began in the 1980s, with discovery that a family in a town in northern Italy had a naturally occurring apolipoprotein A-I variant that mimics the actions of HDL cholesterol, subsequently named ApoA-I_Milano. Despite having low levels of HDL, family members have a reduced risk of coronary disease.

In a small randomized trial, patients with acute coronary syndrome given an early recombinant form of this apolipoprotein saw a reduction in IVUS-measured coronary atherosclerosis (JAMA. 2003;290:2292-300). This prompted development of the refined recombinant form, MDCO-216, tested in the new trial.

“MDCO-216 did not produce a significant effect on coronary disease progression as measured by IVUS,” said Dr. Nicholls, who discussed the findings in a video interview. “These results occurred on a background of contemporary therapy in the post-ACS setting, which in 2016 is very effective for many patients.”

“The findings from this pilot study do not provide the evidence required to proceed with further development,” he concluded.

Hope hinges on wild type

“This trial was extremely well done, world-class investigators carried out this trial, it was three times the size of the previous IVUS trial, and I think it is convincingly negative,” said discussant Daniel J. Rader, MD, associate director of the Institute for Translational Medicine and Therapeutics and director of the Preventive Cardiovascular Program at Penn Medicine, Philadelphia. “The sponsor has elected to stop the development of this product, and I think we can probably write the obituary for ApoA-I_Milano, even though it was never studied in cardiovascular outcomes.”

Trial details

Patients from 22 centers globally were randomized in MILANO-PILOT. All patients had experienced acute coronary syndrome in the past 14 days and had maximum stenosis of 20%-50% of a target vessel on coronary angiography.

NEW ORLEANS – The future doesn’t look bright at the moment for use of agents that mimic HDL cholesterol to reverse coronary disease, based on disappointing results of the randomized, phase II MILANO-PILOT trial.

Among 120 patients with recent acute coronary syndrome, a mimetic known as MDCO-216 was no better than placebo at reducing coronary plaque measured by intravascular ultrasound (IVUS), according to data presented at the American Heart Association scientific sessions.

The median reduction in percent atheroma volume, the trial’s primary endpoint, was 0.5% with the mimetic and 0.8% with placebo, reported Stephen J. Nicholls, MD, of the South Australian Health and Medical Research Institute, University of Adelaide (Australia). Findings were similar for secondary outcomes assessing other measures of disease regression.

These data bring to an end a story that began in the 1980s, with discovery that a family in a town in northern Italy had a naturally occurring apolipoprotein A-I variant that mimics the actions of HDL cholesterol, subsequently named ApoA-I_Milano. Despite having low levels of HDL, family members have a reduced risk of coronary disease.

In a small randomized trial, patients with acute coronary syndrome given an early recombinant form of this apolipoprotein saw a reduction in IVUS-measured coronary atherosclerosis (JAMA. 2003;290:2292-300). This prompted development of the refined recombinant form, MDCO-216, tested in the new trial.

“MDCO-216 did not produce a significant effect on coronary disease progression as measured by IVUS,” said Dr. Nicholls, who discussed the findings in a video interview. “These results occurred on a background of contemporary therapy in the post-ACS setting, which in 2016 is very effective for many patients.”

“The findings from this pilot study do not provide the evidence required to proceed with further development,” he concluded.

Hope hinges on wild type

“This trial was extremely well done, world-class investigators carried out this trial, it was three times the size of the previous IVUS trial, and I think it is convincingly negative,” said discussant Daniel J. Rader, MD, associate director of the Institute for Translational Medicine and Therapeutics and director of the Preventive Cardiovascular Program at Penn Medicine, Philadelphia. “The sponsor has elected to stop the development of this product, and I think we can probably write the obituary for ApoA-I_Milano, even though it was never studied in cardiovascular outcomes.”

Trial details

Patients from 22 centers globally were randomized in MILANO-PILOT. All patients had experienced acute coronary syndrome in the past 14 days and had maximum stenosis of 20%-50% of a target vessel on coronary angiography.

NEW ORLEANS – The future doesn’t look bright at the moment for use of agents that mimic HDL cholesterol to reverse coronary disease, based on disappointing results of the randomized, phase II MILANO-PILOT trial.

Among 120 patients with recent acute coronary syndrome, a mimetic known as MDCO-216 was no better than placebo at reducing coronary plaque measured by intravascular ultrasound (IVUS), according to data presented at the American Heart Association scientific sessions.

The median reduction in percent atheroma volume, the trial’s primary endpoint, was 0.5% with the mimetic and 0.8% with placebo, reported Stephen J. Nicholls, MD, of the South Australian Health and Medical Research Institute, University of Adelaide (Australia). Findings were similar for secondary outcomes assessing other measures of disease regression.

These data bring to an end a story that began in the 1980s, with discovery that a family in a town in northern Italy had a naturally occurring apolipoprotein A-I variant that mimics the actions of HDL cholesterol, subsequently named ApoA-I_Milano. Despite having low levels of HDL, family members have a reduced risk of coronary disease.

In a small randomized trial, patients with acute coronary syndrome given an early recombinant form of this apolipoprotein saw a reduction in IVUS-measured coronary atherosclerosis (JAMA. 2003;290:2292-300). This prompted development of the refined recombinant form, MDCO-216, tested in the new trial.

“MDCO-216 did not produce a significant effect on coronary disease progression as measured by IVUS,” said Dr. Nicholls, who discussed the findings in a video interview. “These results occurred on a background of contemporary therapy in the post-ACS setting, which in 2016 is very effective for many patients.”

“The findings from this pilot study do not provide the evidence required to proceed with further development,” he concluded.

Hope hinges on wild type

“This trial was extremely well done, world-class investigators carried out this trial, it was three times the size of the previous IVUS trial, and I think it is convincingly negative,” said discussant Daniel J. Rader, MD, associate director of the Institute for Translational Medicine and Therapeutics and director of the Preventive Cardiovascular Program at Penn Medicine, Philadelphia. “The sponsor has elected to stop the development of this product, and I think we can probably write the obituary for ApoA-I_Milano, even though it was never studied in cardiovascular outcomes.”

Trial details

Patients from 22 centers globally were randomized in MILANO-PILOT. All patients had experienced acute coronary syndrome in the past 14 days and had maximum stenosis of 20%-50% of a target vessel on coronary angiography.

Over the past several decades, patient-reported outcomes (PROs) have become increasingly important in assessing the quality and effectiveness of medical and surgical care.^1,2 The benefit lies in the ability of PROs to characterize the impact of medical interventions on symptoms, function, and other outcomes from the patient’s perspective. Consequently, clinical practices can improve patients’ objective findings (from radiographic and clinical examinations) as well as their preferences in a social-psychological context.^2,3 As a patient’s satisfaction with a surgical intervention may not correlate with the surgeon’s objective assessment of outcome, PROs offer unique insight into the patient’s perceptions of well-being.⁴

Health-related quality-of-life assessments can be made with either general-health or disease-specific instruments. These instruments traditionally are administered with pen and paper—a data collection method with several limitations, chief being the need to manually transfer the data into an electronic medical record, a research database, or both. In addition, administering surveys on paper risks potential disqualification of partially or incorrectly completed surveys. With pen and paper, it is difficult to mandate that every question be answered accurately.

Currently, there is a potential role for electronic medical records and digital tablet devices in survey administration and data collection and storage. Theoretical advantages include direct input of survey data into databases (eliminating manual data entry and associated entry errors), improved accuracy and completion rates, and long-term storage not dependent on paper charts.⁵To our knowledge, there have been no prospective studies of different orthopedic outcomes collection methods. Some studies have evaluated use of touch-based tablets in data collection. Dy and colleagues⁶ considered administration of the DASH (Disabilities of the Arm, Shoulder, and Hand) survey on an iPad tablet (Apple Computers) and retrospectively compared the tablet and paper completion rates. The tablet group’s rate (98%) was significantly higher than the paper group’s rate (76%). Aktas and colleagues⁷ reported a high completion rate for a tablet survey of palliative care outcomes (they did not compare modalities). A handful of other studies have found higher intraclass correlation and validation for digital data collection than for paper collection.^7-14 The comparability of the data collected digitally vs on paper was the nidus for our decision to prospectively evaluate the ease and reliability of digital data collection.

We conducted a prospective, randomized study to compare the performance of tablet and paper versions of several general-health and musculoskeletal disease–specific questionnaires. We hypothesized the tablet and paper surveys would have similar completion rates and times.

Methods

This study was approved by our Institutional Review Board. Participants were recruited during their clinic visit to 3 subspecialty orthopedic services (upper extremity, spine, arthroplasty). The questionnaires included basic demographics questions and questions about tablet use (comfort level with computers, measured on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree), and ownership of a tablet or smartphone). Also included were European Quality of Life–5 Dimensions (EQ-5D, General Health), a disease questionnaire specific to 1 of the 3 subspecialty services, and a satisfaction survey. Patients were asked to complete the Oswestry Disability Index (ODI) for low-back pain, the Neck Disability Index (NDI) for neck pain, the Hip Disability and Osteoarthritis Outcomes Score (HOOS) for hip pain, the Knee Injury and Osteoarthritis Outcomes Score (KOOS) for knee pain, or the QuickDASH survey for upper extremity complaints (subspecialty-specific). After recruitment, a computer-generated randomization technique was used to randomly assign patients to either a paper or an electronic (iPad) data collection group.¹⁵ We included all surveys for which patients had sufficient completion time (no clinic staff interruptions) and excluded surveys marked incomplete (because of interruptions for clinic workflow efficiency). For direct input from tablets and for data storage, we used the Research Electronic Data Capture (REDCap) system hosted at our institution.¹⁶ Our staff registered patients as REDCap participants, assigned them to their disease-specific study arms, and gave them tablets to use to complete the surveys.

Patients who were randomly assigned to take the surveys on paper were given a packet that included the demographics survey, the EQ-5D, a disease-specific survey, and a satisfaction survey. Their responses were then manually entered by the investigators into the REDCap system.

Patients who were randomly assigned to take the surveys on tablets used the REDCap survey feature, which allowed them to directly input their responses into the database (Figure).

Results

Of the 510 patients enrolled in the study, 483 completed the initial demographics questionnaire and were included in the analysis. Patients were excluded if they were unable to complete the initial demographics questionnaire because of clinic workflow (eg, immediate need to be seen by physician, need to transfer to radiology for imaging and not being able to revisit the survey). Mean age was 56 years (range, 14-93 years), and 51% of the respondents were female. Fifty percent owned tablets, 70% owned smartphones, and mean (SD) self-rating of computer skills was 3.13 (1.16) (Likert scale, 1-5). There were no significant demographic differences between the tablet and paper groups (Table 1).

For each disease-specific questionnaire, the instrument’s published instructions for calculating scores were followed; these scores were then compared in order to further characterize the groups. There were significant differences in scores on the EQ-5D descriptive questions, a pain visual analog scale (VAS), and the NDI. Mean EQ-5D score was 0.664 for the tablet group and 0.699 for the paper group (P = .041), mean pain VAS score was 62.5 for the tablet group and 71.6 for the paper group (P < .001), and mean NDI score was 42.8 for the tablet group and 32.4 for the paper group (P = .033).

Discussion

Electronic data entry has many advantages over traditional paper-based data collection and can be used with PRO surveys to measure response to treatment. Our study evaluated whether completion rates differed between surveys administered on digital tablets and those administered on traditional paper forms in a clinic setting. We selected general-health and disease-specific instruments commonly used to collect PROs from orthopedic patients. Our primary outcome measure was survey completion rate. Secondary outcome measures were total time for completion, number of questions left unanswered on incomplete surveys, patient satisfaction, and survey preferences.

In this study, our tablet and paper groups had similar overall survey completion rates, which suggests digital tablet-based data collection is noninferior to traditional pen-and-paper data collection with respect to patient response rate in the clinical setting. It is worth emphasizing that the tablet surveys were made to resemble and function as much as possible like the paper surveys. For example, patients were allowed to select multiple answers as well as advance without answering a question. Paper surveys were mimicked so we could study inherent differences in patient responsiveness without adding digital features to prevent patients from selecting multiple answers or skipping questions. We postulate that adding these digital features could have introduced a significant difference in patient responsiveness.

Time for survey completion was not significantly different between the tablet and paper groups, demonstrating that data can be digitally collected and the aforementioned advantages realized without significant delay or clinic workflow disruption. In the future, patients may be able to complete their forms digitally, on their own devices, before arriving for their clinic visits—resulting in improved clinic workflow and data collection efficiency.

Scores computed for the health-related quality-of-life questionnaires were not significantly different between the tablet and paper groups, except for EQ-5D and NDI. Although statistically significant, the 0.035 difference between the groups’ EQ-5D scores (0.664, 0.699) is not clinically significant. (Pickard and colleagues¹⁷ established that 0.06 is the clinically significant difference between EQ-5D scores in the United States.) If there were any clinical difference in the present study, our paper group patients appeared to be in better health than our tablet group patients.

Patients’ motivation to complete surveys often plays a large role in meaningful rates of completion. On our subjective satisfaction survey, a larger percentage of patients reported they would prefer to use a tablet for future surveys (Table 4). This finding may be driven by the novelty or ease of using a popular device. Nevertheless, we think it is worthwhile to heed patient preferences, as they may point to more successful data collection and compliance.

Several other studies have compared electronic and paper data capture.^{6,7,9-14,18-22} Dy and colleagues⁶ reported on administering the DASH survey on an iPad tablet using REDCap in an outpatient setting. They found that the percentage of surveys that could be scored (<3 questions left unanswered) was significantly higher for their tablet group (98%) than their paper group (76%). The larger difference in survey completion rates in their study (vs ours) may be attributable to their use of DASH, which has more survey items (compared with QuickDASH, the instrument we used) and thus may be more sensitive to detecting differences, at the risk of increasing the burden on survey takers.²³ Aktas and colleagues⁷ conducted a similar but smaller study of completion rates, completion times, and overall practicality of using digital tablets to collect PROs in a palliative care clinic (they did not compare tablet and paper modalities). Marsh and colleagues,¹² who studied the agreement between data collected on electronic and paper versions of the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index and the SF-12 (12-item Short Form Health Survey, Version 2) after total hip and total knee arthroplasty, found a high intraclass correlation coefficient between the 2 methods. Griffiths-Jones and colleagues¹¹ also found a high degree of agreement between patient data collected on digital and paper surveys. In a similar study, Fanning and McAuley¹⁰ compared digital tablet and paper survey administration in an older population and found a higher percentage of preference for tablets, with ease of use and anxiety during survey completion correlating with preference. These findings mirror ours, even with our inclusion of patients in a broader age range.

Strengths of our study included its overall cohort size and the variety of measurement instruments used. In addition, we measured time for survey completion to assess the practicality of tablet-based data collection and refrained from using digital features that could have artificially improved the completion rate for this survey modality.

Our study had a few limitations. First, we recruited unequal numbers of patients from the different subspecialties—a result of each subspecialty having a different number of attending physicians and a different patient volume. Given randomization and use of similar patients across the study arms, however, this likely did not present any significant bias. Second, each patient completed a tablet survey or a paper survey but not both, and therefore we could not compare a patient’s performance on the 2 modalities. However, the burden of completing the same survey more than once likely would have lowered our participation rate and introduced additional biases we wanted to avoid. Third, despite our attempt to mimic the look of a paper survey, the tablet’s user interface presented several potential difficulties. For example, its small text and small answer buttons may have been limiting for patients with poor vision. These design features emphasize the importance of having a user interface that can be adapted to the individual, regardless of handicap. Indeed, adaptability is a potential strength of digital interfaces. For adaptability, an interface designer can use large, scalable text and add audio prompts and other features.

Our findings can be useful in evaluating patient responsiveness to surveys administered on digital tablets in an outpatient clinic setting. In this prospective, randomized study, we found that, for survey completion, use of a tablet device did not require more time than use of a paper form. In addition, the administration modalities had similar completion and error rates for a variety of orthopedic outcomes surveys. We did not activate digital features that would have given unfair advantage to the digital data collection modality. We also found a strong preference for use of technology in PRO data collection, and this may help improve collection rates. Last, though optimizing the flow of patients in our clinic was not a strict research metric, we prioritized making sure patients were not spending any more time completing these surveys than in the past. Given the potential benefits of digital surveys—immediate and accurate transfer of collected data into multiple databases, including the patient’s electronic medical record—our experience supports continuing validation of these instruments for potential wider use.

Am J Orthop. 2016;45(7):E451-E457. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Over the past several decades, patient-reported outcomes (PROs) have become increasingly important in assessing the quality and effectiveness of medical and surgical care.^1,2 The benefit lies in the ability of PROs to characterize the impact of medical interventions on symptoms, function, and other outcomes from the patient’s perspective. Consequently, clinical practices can improve patients’ objective findings (from radiographic and clinical examinations) as well as their preferences in a social-psychological context.^2,3 As a patient’s satisfaction with a surgical intervention may not correlate with the surgeon’s objective assessment of outcome, PROs offer unique insight into the patient’s perceptions of well-being.⁴

Health-related quality-of-life assessments can be made with either general-health or disease-specific instruments. These instruments traditionally are administered with pen and paper—a data collection method with several limitations, chief being the need to manually transfer the data into an electronic medical record, a research database, or both. In addition, administering surveys on paper risks potential disqualification of partially or incorrectly completed surveys. With pen and paper, it is difficult to mandate that every question be answered accurately.

Currently, there is a potential role for electronic medical records and digital tablet devices in survey administration and data collection and storage. Theoretical advantages include direct input of survey data into databases (eliminating manual data entry and associated entry errors), improved accuracy and completion rates, and long-term storage not dependent on paper charts.⁵To our knowledge, there have been no prospective studies of different orthopedic outcomes collection methods. Some studies have evaluated use of touch-based tablets in data collection. Dy and colleagues⁶ considered administration of the DASH (Disabilities of the Arm, Shoulder, and Hand) survey on an iPad tablet (Apple Computers) and retrospectively compared the tablet and paper completion rates. The tablet group’s rate (98%) was significantly higher than the paper group’s rate (76%). Aktas and colleagues⁷ reported a high completion rate for a tablet survey of palliative care outcomes (they did not compare modalities). A handful of other studies have found higher intraclass correlation and validation for digital data collection than for paper collection.^7-14 The comparability of the data collected digitally vs on paper was the nidus for our decision to prospectively evaluate the ease and reliability of digital data collection.

We conducted a prospective, randomized study to compare the performance of tablet and paper versions of several general-health and musculoskeletal disease–specific questionnaires. We hypothesized the tablet and paper surveys would have similar completion rates and times.

Methods

This study was approved by our Institutional Review Board. Participants were recruited during their clinic visit to 3 subspecialty orthopedic services (upper extremity, spine, arthroplasty). The questionnaires included basic demographics questions and questions about tablet use (comfort level with computers, measured on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree), and ownership of a tablet or smartphone). Also included were European Quality of Life–5 Dimensions (EQ-5D, General Health), a disease questionnaire specific to 1 of the 3 subspecialty services, and a satisfaction survey. Patients were asked to complete the Oswestry Disability Index (ODI) for low-back pain, the Neck Disability Index (NDI) for neck pain, the Hip Disability and Osteoarthritis Outcomes Score (HOOS) for hip pain, the Knee Injury and Osteoarthritis Outcomes Score (KOOS) for knee pain, or the QuickDASH survey for upper extremity complaints (subspecialty-specific). After recruitment, a computer-generated randomization technique was used to randomly assign patients to either a paper or an electronic (iPad) data collection group.¹⁵ We included all surveys for which patients had sufficient completion time (no clinic staff interruptions) and excluded surveys marked incomplete (because of interruptions for clinic workflow efficiency). For direct input from tablets and for data storage, we used the Research Electronic Data Capture (REDCap) system hosted at our institution.¹⁶ Our staff registered patients as REDCap participants, assigned them to their disease-specific study arms, and gave them tablets to use to complete the surveys.

Patients who were randomly assigned to take the surveys on paper were given a packet that included the demographics survey, the EQ-5D, a disease-specific survey, and a satisfaction survey. Their responses were then manually entered by the investigators into the REDCap system.

Patients who were randomly assigned to take the surveys on tablets used the REDCap survey feature, which allowed them to directly input their responses into the database (Figure).

Results

Of the 510 patients enrolled in the study, 483 completed the initial demographics questionnaire and were included in the analysis. Patients were excluded if they were unable to complete the initial demographics questionnaire because of clinic workflow (eg, immediate need to be seen by physician, need to transfer to radiology for imaging and not being able to revisit the survey). Mean age was 56 years (range, 14-93 years), and 51% of the respondents were female. Fifty percent owned tablets, 70% owned smartphones, and mean (SD) self-rating of computer skills was 3.13 (1.16) (Likert scale, 1-5). There were no significant demographic differences between the tablet and paper groups (Table 1).

For each disease-specific questionnaire, the instrument’s published instructions for calculating scores were followed; these scores were then compared in order to further characterize the groups. There were significant differences in scores on the EQ-5D descriptive questions, a pain visual analog scale (VAS), and the NDI. Mean EQ-5D score was 0.664 for the tablet group and 0.699 for the paper group (P = .041), mean pain VAS score was 62.5 for the tablet group and 71.6 for the paper group (P < .001), and mean NDI score was 42.8 for the tablet group and 32.4 for the paper group (P = .033).

Discussion

Electronic data entry has many advantages over traditional paper-based data collection and can be used with PRO surveys to measure response to treatment. Our study evaluated whether completion rates differed between surveys administered on digital tablets and those administered on traditional paper forms in a clinic setting. We selected general-health and disease-specific instruments commonly used to collect PROs from orthopedic patients. Our primary outcome measure was survey completion rate. Secondary outcome measures were total time for completion, number of questions left unanswered on incomplete surveys, patient satisfaction, and survey preferences.

In this study, our tablet and paper groups had similar overall survey completion rates, which suggests digital tablet-based data collection is noninferior to traditional pen-and-paper data collection with respect to patient response rate in the clinical setting. It is worth emphasizing that the tablet surveys were made to resemble and function as much as possible like the paper surveys. For example, patients were allowed to select multiple answers as well as advance without answering a question. Paper surveys were mimicked so we could study inherent differences in patient responsiveness without adding digital features to prevent patients from selecting multiple answers or skipping questions. We postulate that adding these digital features could have introduced a significant difference in patient responsiveness.

Time for survey completion was not significantly different between the tablet and paper groups, demonstrating that data can be digitally collected and the aforementioned advantages realized without significant delay or clinic workflow disruption. In the future, patients may be able to complete their forms digitally, on their own devices, before arriving for their clinic visits—resulting in improved clinic workflow and data collection efficiency.

Scores computed for the health-related quality-of-life questionnaires were not significantly different between the tablet and paper groups, except for EQ-5D and NDI. Although statistically significant, the 0.035 difference between the groups’ EQ-5D scores (0.664, 0.699) is not clinically significant. (Pickard and colleagues¹⁷ established that 0.06 is the clinically significant difference between EQ-5D scores in the United States.) If there were any clinical difference in the present study, our paper group patients appeared to be in better health than our tablet group patients.

Patients’ motivation to complete surveys often plays a large role in meaningful rates of completion. On our subjective satisfaction survey, a larger percentage of patients reported they would prefer to use a tablet for future surveys (Table 4). This finding may be driven by the novelty or ease of using a popular device. Nevertheless, we think it is worthwhile to heed patient preferences, as they may point to more successful data collection and compliance.

Several other studies have compared electronic and paper data capture.^{6,7,9-14,18-22} Dy and colleagues⁶ reported on administering the DASH survey on an iPad tablet using REDCap in an outpatient setting. They found that the percentage of surveys that could be scored (<3 questions left unanswered) was significantly higher for their tablet group (98%) than their paper group (76%). The larger difference in survey completion rates in their study (vs ours) may be attributable to their use of DASH, which has more survey items (compared with QuickDASH, the instrument we used) and thus may be more sensitive to detecting differences, at the risk of increasing the burden on survey takers.²³ Aktas and colleagues⁷ conducted a similar but smaller study of completion rates, completion times, and overall practicality of using digital tablets to collect PROs in a palliative care clinic (they did not compare tablet and paper modalities). Marsh and colleagues,¹² who studied the agreement between data collected on electronic and paper versions of the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index and the SF-12 (12-item Short Form Health Survey, Version 2) after total hip and total knee arthroplasty, found a high intraclass correlation coefficient between the 2 methods. Griffiths-Jones and colleagues¹¹ also found a high degree of agreement between patient data collected on digital and paper surveys. In a similar study, Fanning and McAuley¹⁰ compared digital tablet and paper survey administration in an older population and found a higher percentage of preference for tablets, with ease of use and anxiety during survey completion correlating with preference. These findings mirror ours, even with our inclusion of patients in a broader age range.

Strengths of our study included its overall cohort size and the variety of measurement instruments used. In addition, we measured time for survey completion to assess the practicality of tablet-based data collection and refrained from using digital features that could have artificially improved the completion rate for this survey modality.

Our study had a few limitations. First, we recruited unequal numbers of patients from the different subspecialties—a result of each subspecialty having a different number of attending physicians and a different patient volume. Given randomization and use of similar patients across the study arms, however, this likely did not present any significant bias. Second, each patient completed a tablet survey or a paper survey but not both, and therefore we could not compare a patient’s performance on the 2 modalities. However, the burden of completing the same survey more than once likely would have lowered our participation rate and introduced additional biases we wanted to avoid. Third, despite our attempt to mimic the look of a paper survey, the tablet’s user interface presented several potential difficulties. For example, its small text and small answer buttons may have been limiting for patients with poor vision. These design features emphasize the importance of having a user interface that can be adapted to the individual, regardless of handicap. Indeed, adaptability is a potential strength of digital interfaces. For adaptability, an interface designer can use large, scalable text and add audio prompts and other features.

Our findings can be useful in evaluating patient responsiveness to surveys administered on digital tablets in an outpatient clinic setting. In this prospective, randomized study, we found that, for survey completion, use of a tablet device did not require more time than use of a paper form. In addition, the administration modalities had similar completion and error rates for a variety of orthopedic outcomes surveys. We did not activate digital features that would have given unfair advantage to the digital data collection modality. We also found a strong preference for use of technology in PRO data collection, and this may help improve collection rates. Last, though optimizing the flow of patients in our clinic was not a strict research metric, we prioritized making sure patients were not spending any more time completing these surveys than in the past. Given the potential benefits of digital surveys—immediate and accurate transfer of collected data into multiple databases, including the patient’s electronic medical record—our experience supports continuing validation of these instruments for potential wider use.

Am J Orthop. 2016;45(7):E451-E457. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Over the past several decades, patient-reported outcomes (PROs) have become increasingly important in assessing the quality and effectiveness of medical and surgical care.^1,2 The benefit lies in the ability of PROs to characterize the impact of medical interventions on symptoms, function, and other outcomes from the patient’s perspective. Consequently, clinical practices can improve patients’ objective findings (from radiographic and clinical examinations) as well as their preferences in a social-psychological context.^2,3 As a patient’s satisfaction with a surgical intervention may not correlate with the surgeon’s objective assessment of outcome, PROs offer unique insight into the patient’s perceptions of well-being.⁴

Health-related quality-of-life assessments can be made with either general-health or disease-specific instruments. These instruments traditionally are administered with pen and paper—a data collection method with several limitations, chief being the need to manually transfer the data into an electronic medical record, a research database, or both. In addition, administering surveys on paper risks potential disqualification of partially or incorrectly completed surveys. With pen and paper, it is difficult to mandate that every question be answered accurately.

Currently, there is a potential role for electronic medical records and digital tablet devices in survey administration and data collection and storage. Theoretical advantages include direct input of survey data into databases (eliminating manual data entry and associated entry errors), improved accuracy and completion rates, and long-term storage not dependent on paper charts.⁵To our knowledge, there have been no prospective studies of different orthopedic outcomes collection methods. Some studies have evaluated use of touch-based tablets in data collection. Dy and colleagues⁶ considered administration of the DASH (Disabilities of the Arm, Shoulder, and Hand) survey on an iPad tablet (Apple Computers) and retrospectively compared the tablet and paper completion rates. The tablet group’s rate (98%) was significantly higher than the paper group’s rate (76%). Aktas and colleagues⁷ reported a high completion rate for a tablet survey of palliative care outcomes (they did not compare modalities). A handful of other studies have found higher intraclass correlation and validation for digital data collection than for paper collection.^7-14 The comparability of the data collected digitally vs on paper was the nidus for our decision to prospectively evaluate the ease and reliability of digital data collection.

We conducted a prospective, randomized study to compare the performance of tablet and paper versions of several general-health and musculoskeletal disease–specific questionnaires. We hypothesized the tablet and paper surveys would have similar completion rates and times.

Methods

This study was approved by our Institutional Review Board. Participants were recruited during their clinic visit to 3 subspecialty orthopedic services (upper extremity, spine, arthroplasty). The questionnaires included basic demographics questions and questions about tablet use (comfort level with computers, measured on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree), and ownership of a tablet or smartphone). Also included were European Quality of Life–5 Dimensions (EQ-5D, General Health), a disease questionnaire specific to 1 of the 3 subspecialty services, and a satisfaction survey. Patients were asked to complete the Oswestry Disability Index (ODI) for low-back pain, the Neck Disability Index (NDI) for neck pain, the Hip Disability and Osteoarthritis Outcomes Score (HOOS) for hip pain, the Knee Injury and Osteoarthritis Outcomes Score (KOOS) for knee pain, or the QuickDASH survey for upper extremity complaints (subspecialty-specific). After recruitment, a computer-generated randomization technique was used to randomly assign patients to either a paper or an electronic (iPad) data collection group.¹⁵ We included all surveys for which patients had sufficient completion time (no clinic staff interruptions) and excluded surveys marked incomplete (because of interruptions for clinic workflow efficiency). For direct input from tablets and for data storage, we used the Research Electronic Data Capture (REDCap) system hosted at our institution.¹⁶ Our staff registered patients as REDCap participants, assigned them to their disease-specific study arms, and gave them tablets to use to complete the surveys.

Patients who were randomly assigned to take the surveys on paper were given a packet that included the demographics survey, the EQ-5D, a disease-specific survey, and a satisfaction survey. Their responses were then manually entered by the investigators into the REDCap system.

Patients who were randomly assigned to take the surveys on tablets used the REDCap survey feature, which allowed them to directly input their responses into the database (Figure).

Results

Of the 510 patients enrolled in the study, 483 completed the initial demographics questionnaire and were included in the analysis. Patients were excluded if they were unable to complete the initial demographics questionnaire because of clinic workflow (eg, immediate need to be seen by physician, need to transfer to radiology for imaging and not being able to revisit the survey). Mean age was 56 years (range, 14-93 years), and 51% of the respondents were female. Fifty percent owned tablets, 70% owned smartphones, and mean (SD) self-rating of computer skills was 3.13 (1.16) (Likert scale, 1-5). There were no significant demographic differences between the tablet and paper groups (Table 1).

For each disease-specific questionnaire, the instrument’s published instructions for calculating scores were followed; these scores were then compared in order to further characterize the groups. There were significant differences in scores on the EQ-5D descriptive questions, a pain visual analog scale (VAS), and the NDI. Mean EQ-5D score was 0.664 for the tablet group and 0.699 for the paper group (P = .041), mean pain VAS score was 62.5 for the tablet group and 71.6 for the paper group (P < .001), and mean NDI score was 42.8 for the tablet group and 32.4 for the paper group (P = .033).

Discussion

Electronic data entry has many advantages over traditional paper-based data collection and can be used with PRO surveys to measure response to treatment. Our study evaluated whether completion rates differed between surveys administered on digital tablets and those administered on traditional paper forms in a clinic setting. We selected general-health and disease-specific instruments commonly used to collect PROs from orthopedic patients. Our primary outcome measure was survey completion rate. Secondary outcome measures were total time for completion, number of questions left unanswered on incomplete surveys, patient satisfaction, and survey preferences.

In this study, our tablet and paper groups had similar overall survey completion rates, which suggests digital tablet-based data collection is noninferior to traditional pen-and-paper data collection with respect to patient response rate in the clinical setting. It is worth emphasizing that the tablet surveys were made to resemble and function as much as possible like the paper surveys. For example, patients were allowed to select multiple answers as well as advance without answering a question. Paper surveys were mimicked so we could study inherent differences in patient responsiveness without adding digital features to prevent patients from selecting multiple answers or skipping questions. We postulate that adding these digital features could have introduced a significant difference in patient responsiveness.

Time for survey completion was not significantly different between the tablet and paper groups, demonstrating that data can be digitally collected and the aforementioned advantages realized without significant delay or clinic workflow disruption. In the future, patients may be able to complete their forms digitally, on their own devices, before arriving for their clinic visits—resulting in improved clinic workflow and data collection efficiency.

Scores computed for the health-related quality-of-life questionnaires were not significantly different between the tablet and paper groups, except for EQ-5D and NDI. Although statistically significant, the 0.035 difference between the groups’ EQ-5D scores (0.664, 0.699) is not clinically significant. (Pickard and colleagues¹⁷ established that 0.06 is the clinically significant difference between EQ-5D scores in the United States.) If there were any clinical difference in the present study, our paper group patients appeared to be in better health than our tablet group patients.

Patients’ motivation to complete surveys often plays a large role in meaningful rates of completion. On our subjective satisfaction survey, a larger percentage of patients reported they would prefer to use a tablet for future surveys (Table 4). This finding may be driven by the novelty or ease of using a popular device. Nevertheless, we think it is worthwhile to heed patient preferences, as they may point to more successful data collection and compliance.

Several other studies have compared electronic and paper data capture.^{6,7,9-14,18-22} Dy and colleagues⁶ reported on administering the DASH survey on an iPad tablet using REDCap in an outpatient setting. They found that the percentage of surveys that could be scored (<3 questions left unanswered) was significantly higher for their tablet group (98%) than their paper group (76%). The larger difference in survey completion rates in their study (vs ours) may be attributable to their use of DASH, which has more survey items (compared with QuickDASH, the instrument we used) and thus may be more sensitive to detecting differences, at the risk of increasing the burden on survey takers.²³ Aktas and colleagues⁷ conducted a similar but smaller study of completion rates, completion times, and overall practicality of using digital tablets to collect PROs in a palliative care clinic (they did not compare tablet and paper modalities). Marsh and colleagues,¹² who studied the agreement between data collected on electronic and paper versions of the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index and the SF-12 (12-item Short Form Health Survey, Version 2) after total hip and total knee arthroplasty, found a high intraclass correlation coefficient between the 2 methods. Griffiths-Jones and colleagues¹¹ also found a high degree of agreement between patient data collected on digital and paper surveys. In a similar study, Fanning and McAuley¹⁰ compared digital tablet and paper survey administration in an older population and found a higher percentage of preference for tablets, with ease of use and anxiety during survey completion correlating with preference. These findings mirror ours, even with our inclusion of patients in a broader age range.

Strengths of our study included its overall cohort size and the variety of measurement instruments used. In addition, we measured time for survey completion to assess the practicality of tablet-based data collection and refrained from using digital features that could have artificially improved the completion rate for this survey modality.

Our study had a few limitations. First, we recruited unequal numbers of patients from the different subspecialties—a result of each subspecialty having a different number of attending physicians and a different patient volume. Given randomization and use of similar patients across the study arms, however, this likely did not present any significant bias. Second, each patient completed a tablet survey or a paper survey but not both, and therefore we could not compare a patient’s performance on the 2 modalities. However, the burden of completing the same survey more than once likely would have lowered our participation rate and introduced additional biases we wanted to avoid. Third, despite our attempt to mimic the look of a paper survey, the tablet’s user interface presented several potential difficulties. For example, its small text and small answer buttons may have been limiting for patients with poor vision. These design features emphasize the importance of having a user interface that can be adapted to the individual, regardless of handicap. Indeed, adaptability is a potential strength of digital interfaces. For adaptability, an interface designer can use large, scalable text and add audio prompts and other features.

Our findings can be useful in evaluating patient responsiveness to surveys administered on digital tablets in an outpatient clinic setting. In this prospective, randomized study, we found that, for survey completion, use of a tablet device did not require more time than use of a paper form. In addition, the administration modalities had similar completion and error rates for a variety of orthopedic outcomes surveys. We did not activate digital features that would have given unfair advantage to the digital data collection modality. We also found a strong preference for use of technology in PRO data collection, and this may help improve collection rates. Last, though optimizing the flow of patients in our clinic was not a strict research metric, we prioritized making sure patients were not spending any more time completing these surveys than in the past. Given the potential benefits of digital surveys—immediate and accurate transfer of collected data into multiple databases, including the patient’s electronic medical record—our experience supports continuing validation of these instruments for potential wider use.

Am J Orthop. 2016;45(7):E451-E457. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

WASHINGTON – Acting Administrator Andy Slavitt has some advice for his successors at the CMS: Keep the Center for Medicare & Medicaid Innovation, even if you trash the Affordable Care Act.

The innovation center is vital to the success of the Quality Payment Program, the value-based payment framework set up by the Medicare Access and CHIP Reauthorization Act (MACRA), Mr. Slavitt said Dec. 1 at the National MACRA MIPS/APM Summit.

Gregory Twachtman/Frontline Medical News

Mr. Slavitt offered a few other recommendations to the next regime. First, he called on the Trump administration to ensure that the 20 million people who have obtained health care coverage under the ACA do not lose it as a key to continued delivery system reform.

“Build from a foundation of progress, do not head backwards,” Mr. Slavitt advised. “There can be no delivery system reform without building on the foundation of reaching universal coverage.”

To that end, he advised keeping other key ACA provisions, including no-cost preventive care, the elimination of annual and lifetime coverage caps, and the end of pre-existing condition exclusions.

“If we want to fix how care is delivered, so that we’re providing value, then we must ensure that Americans can afford and access quality care at every point in their lives,” he said. “If we lose even some of the coverage gains made under the ACA, or leave people in limbo, people will lose access to regular care and we will drive up long-term costs.”

He also called for more improvements in the health IT space, including a demand for affordable systems and technologies that can exchange data and support quality health care.

“MACRA is an opportunity to move the focus away from paperwork and reporting and toward paying for what works,” Mr. Slavitt said. “For a variety of reasons, EHRs became an industry before they became a useful tool. The technology community must be held accountable ... to make room for new innovators and to give clinicians more freedom and more flexibility to focus on their patients, to practice medicine, and deliver better care.”

President-elect Trump has designated Seema Verma, a health care consultant who helped design the Indiana’s ACA Medicaid expansion, to be the next CMS administrator.

[email protected]

WASHINGTON – Acting Administrator Andy Slavitt has some advice for his successors at the CMS: Keep the Center for Medicare & Medicaid Innovation, even if you trash the Affordable Care Act.

The innovation center is vital to the success of the Quality Payment Program, the value-based payment framework set up by the Medicare Access and CHIP Reauthorization Act (MACRA), Mr. Slavitt said Dec. 1 at the National MACRA MIPS/APM Summit.

Gregory Twachtman/Frontline Medical News

Mr. Slavitt offered a few other recommendations to the next regime. First, he called on the Trump administration to ensure that the 20 million people who have obtained health care coverage under the ACA do not lose it as a key to continued delivery system reform.

“Build from a foundation of progress, do not head backwards,” Mr. Slavitt advised. “There can be no delivery system reform without building on the foundation of reaching universal coverage.”

To that end, he advised keeping other key ACA provisions, including no-cost preventive care, the elimination of annual and lifetime coverage caps, and the end of pre-existing condition exclusions.

“If we want to fix how care is delivered, so that we’re providing value, then we must ensure that Americans can afford and access quality care at every point in their lives,” he said. “If we lose even some of the coverage gains made under the ACA, or leave people in limbo, people will lose access to regular care and we will drive up long-term costs.”

He also called for more improvements in the health IT space, including a demand for affordable systems and technologies that can exchange data and support quality health care.

“MACRA is an opportunity to move the focus away from paperwork and reporting and toward paying for what works,” Mr. Slavitt said. “For a variety of reasons, EHRs became an industry before they became a useful tool. The technology community must be held accountable ... to make room for new innovators and to give clinicians more freedom and more flexibility to focus on their patients, to practice medicine, and deliver better care.”

President-elect Trump has designated Seema Verma, a health care consultant who helped design the Indiana’s ACA Medicaid expansion, to be the next CMS administrator.

[email protected]

WASHINGTON – Acting Administrator Andy Slavitt has some advice for his successors at the CMS: Keep the Center for Medicare & Medicaid Innovation, even if you trash the Affordable Care Act.

The innovation center is vital to the success of the Quality Payment Program, the value-based payment framework set up by the Medicare Access and CHIP Reauthorization Act (MACRA), Mr. Slavitt said Dec. 1 at the National MACRA MIPS/APM Summit.

Gregory Twachtman/Frontline Medical News

Mr. Slavitt offered a few other recommendations to the next regime. First, he called on the Trump administration to ensure that the 20 million people who have obtained health care coverage under the ACA do not lose it as a key to continued delivery system reform.

“Build from a foundation of progress, do not head backwards,” Mr. Slavitt advised. “There can be no delivery system reform without building on the foundation of reaching universal coverage.”

To that end, he advised keeping other key ACA provisions, including no-cost preventive care, the elimination of annual and lifetime coverage caps, and the end of pre-existing condition exclusions.

“If we want to fix how care is delivered, so that we’re providing value, then we must ensure that Americans can afford and access quality care at every point in their lives,” he said. “If we lose even some of the coverage gains made under the ACA, or leave people in limbo, people will lose access to regular care and we will drive up long-term costs.”

He also called for more improvements in the health IT space, including a demand for affordable systems and technologies that can exchange data and support quality health care.

“MACRA is an opportunity to move the focus away from paperwork and reporting and toward paying for what works,” Mr. Slavitt said. “For a variety of reasons, EHRs became an industry before they became a useful tool. The technology community must be held accountable ... to make room for new innovators and to give clinicians more freedom and more flexibility to focus on their patients, to practice medicine, and deliver better care.”

President-elect Trump has designated Seema Verma, a health care consultant who helped design the Indiana’s ACA Medicaid expansion, to be the next CMS administrator.

[email protected]

Q2: Answer: B

Rationale: This patient has a sessile serrated polyp without dysplasia located in the right colon as well as hyperplastic polyps in the rectosigmoid. Serrated polyps are thought to be precursor lesions to colon cancers arising from gene hypermethylation. Serrated polyps may be difficult to detect as they are flat or sessile, have indiscrete borders, and adherent mucus. Recent guidelines from the Multi-Society Task Force recommend that these lesions be treated in a way similar to that of adenomas for surveillance. Serrated polyps less than 10 mm without dysplasia should be surveyed in 5 years. Serrated polyps greater than 10 mm with or without dysplasia should be managed in a way similar to that of high-risk adenomas, with surveillance in 3 years. Hyperplastic polyps in the rectum do not require intensified surveillance.

Reference

1. Lieberman, D.A., Rex, D.K., Winawer, S.J., et al. Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844.

Q2: Answer: B

Rationale: This patient has a sessile serrated polyp without dysplasia located in the right colon as well as hyperplastic polyps in the rectosigmoid. Serrated polyps are thought to be precursor lesions to colon cancers arising from gene hypermethylation. Serrated polyps may be difficult to detect as they are flat or sessile, have indiscrete borders, and adherent mucus. Recent guidelines from the Multi-Society Task Force recommend that these lesions be treated in a way similar to that of adenomas for surveillance. Serrated polyps less than 10 mm without dysplasia should be surveyed in 5 years. Serrated polyps greater than 10 mm with or without dysplasia should be managed in a way similar to that of high-risk adenomas, with surveillance in 3 years. Hyperplastic polyps in the rectum do not require intensified surveillance.

Reference

1. Lieberman, D.A., Rex, D.K., Winawer, S.J., et al. Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844.

Q2: Answer: B

Rationale: This patient has a sessile serrated polyp without dysplasia located in the right colon as well as hyperplastic polyps in the rectosigmoid. Serrated polyps are thought to be precursor lesions to colon cancers arising from gene hypermethylation. Serrated polyps may be difficult to detect as they are flat or sessile, have indiscrete borders, and adherent mucus. Recent guidelines from the Multi-Society Task Force recommend that these lesions be treated in a way similar to that of adenomas for surveillance. Serrated polyps less than 10 mm without dysplasia should be surveyed in 5 years. Serrated polyps greater than 10 mm with or without dysplasia should be managed in a way similar to that of high-risk adenomas, with surveillance in 3 years. Hyperplastic polyps in the rectum do not require intensified surveillance.

Reference

1. Lieberman, D.A., Rex, D.K., Winawer, S.J., et al. Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844.

The Diagnosis: Metastatic Renal Cell Carcinoma

A shave biopsy of the right occipital scalp lesion demonstrated large clear cells arranged in oval nests with mildly atypical central nuclei (Figure). The findings were consistent with the clear cell type of metastatic renal cell carcinoma (mRCC) with tumor involvement in the deep margin. PAX8 immunostain was positive in the tumor, further supporting the diagnosis of mRCC.

The most common patient demographic diagnosed with renal cell carcinoma (RCC) is men in the sixth and seventh decades of life.^1,2 The classic presentation of RCC includes the triad of flank pain, hematuria, and a palpable abdominal mass. Other symptoms may include fatigue, weight loss, and anemia; however, small localized tumors rarely are symptomatic, and less than 10% of patients with RCC present with this classic triad.³ Many RCCs are diagnosed from incidental findings on abdominal imaging or from the presentation of metastatic disease.^1,2 The lungs, bones, and liver are the most common sites of metastases, while skin metastases are rare.² One study found only 3.3% (10/306) of RCC cases had cutaneous metastases and the scalp was the most common location. In half of these patients, the skin metastases were present at initial RCC diagnosis.⁴

The most common presentation of a cutaneous metastasis of RCC entails the rapid development of a reddish blue nodule on the face or scalp.^4,5 The differential diagnosis may include basal cell carcinoma, hemangioma, cutaneous angiosarcoma, pyogenic granuloma, and atypical fibroxanthoma. Careful elicitation of a medical history indicating any of the classic or systemic signs associated with RCC or a personal history of RCC should raise the suspicion for mRCC and prompt a biopsy.

Clear cell RCC is the most common type of primary RCC and 81% of mRCCs were found to be of the clear cell type. Clear cell RCC classically exhibits clear ballooned cytoplasm with distinct cell borders.⁶ Immunohistochemistry stains with PAX2 and PAX8 are helpful in diagnosing the renal origin of the metastatic tissue, with PAX8 being especially helpful (89% sensitivity).⁷

The von Hippel-Lindau gene, VHL, is involved in up to 60% of sporadic clear cell RCC cases, in addition to its involvement in VHL syndrome.1 von Hippel-Lindau syndrome is associated with clear cell RCC, retinal angiomas, hemangioblastomas of the central nervous system, and pheochromocytomas.¹ The mutated VHL gene is associated with an increased expression of vascular endothelial growth factor (VEGF), which promotes angiogenesis, endothelial mutagenesis, and vascular permeability.⁸ These physiologic responses are likely responsible for the proliferation and dissemination of neoplastic cells in clear cell RCC.⁹ The understanding of this pathogenic mechanism has led to the development of targeted effective treatments in RCC.

Systemic treatments for mRCC are rapidly evolving and improving.⁹ Vascular endothelial growth factor tyrosine kinase inhibitors such as sorafenib, sunitinib, and pazopanib, as well as the VEGF monoclonal antibody bevacizumab, have all demonstrated notable efficacy in the treatment of RCC. Phase 3 clinical trials for the treatment of mRCC have demonstrated that the new, more biochemically potent VEGF tyrosine kinase inhibitor axitinib has superior efficacy to sorafenib, the prior standard of care.⁹ Our patient noted that the cutaneous mRCC lesion seemed to be improving after starting treatment with axitinib 2 months prior to presentation. In addition to systemic chemotherapy, the surgical removal of lesions often is indicated for the treatment of cutaneous mRCC.^5,10 Our patient has continued axitinib and is doing well.

The Diagnosis: Metastatic Renal Cell Carcinoma

A shave biopsy of the right occipital scalp lesion demonstrated large clear cells arranged in oval nests with mildly atypical central nuclei (Figure). The findings were consistent with the clear cell type of metastatic renal cell carcinoma (mRCC) with tumor involvement in the deep margin. PAX8 immunostain was positive in the tumor, further supporting the diagnosis of mRCC.

The most common patient demographic diagnosed with renal cell carcinoma (RCC) is men in the sixth and seventh decades of life.^1,2 The classic presentation of RCC includes the triad of flank pain, hematuria, and a palpable abdominal mass. Other symptoms may include fatigue, weight loss, and anemia; however, small localized tumors rarely are symptomatic, and less than 10% of patients with RCC present with this classic triad.³ Many RCCs are diagnosed from incidental findings on abdominal imaging or from the presentation of metastatic disease.^1,2 The lungs, bones, and liver are the most common sites of metastases, while skin metastases are rare.² One study found only 3.3% (10/306) of RCC cases had cutaneous metastases and the scalp was the most common location. In half of these patients, the skin metastases were present at initial RCC diagnosis.⁴

The most common presentation of a cutaneous metastasis of RCC entails the rapid development of a reddish blue nodule on the face or scalp.^4,5 The differential diagnosis may include basal cell carcinoma, hemangioma, cutaneous angiosarcoma, pyogenic granuloma, and atypical fibroxanthoma. Careful elicitation of a medical history indicating any of the classic or systemic signs associated with RCC or a personal history of RCC should raise the suspicion for mRCC and prompt a biopsy.

Clear cell RCC is the most common type of primary RCC and 81% of mRCCs were found to be of the clear cell type. Clear cell RCC classically exhibits clear ballooned cytoplasm with distinct cell borders.⁶ Immunohistochemistry stains with PAX2 and PAX8 are helpful in diagnosing the renal origin of the metastatic tissue, with PAX8 being especially helpful (89% sensitivity).⁷

The von Hippel-Lindau gene, VHL, is involved in up to 60% of sporadic clear cell RCC cases, in addition to its involvement in VHL syndrome.1 von Hippel-Lindau syndrome is associated with clear cell RCC, retinal angiomas, hemangioblastomas of the central nervous system, and pheochromocytomas.¹ The mutated VHL gene is associated with an increased expression of vascular endothelial growth factor (VEGF), which promotes angiogenesis, endothelial mutagenesis, and vascular permeability.⁸ These physiologic responses are likely responsible for the proliferation and dissemination of neoplastic cells in clear cell RCC.⁹ The understanding of this pathogenic mechanism has led to the development of targeted effective treatments in RCC.

Systemic treatments for mRCC are rapidly evolving and improving.⁹ Vascular endothelial growth factor tyrosine kinase inhibitors such as sorafenib, sunitinib, and pazopanib, as well as the VEGF monoclonal antibody bevacizumab, have all demonstrated notable efficacy in the treatment of RCC. Phase 3 clinical trials for the treatment of mRCC have demonstrated that the new, more biochemically potent VEGF tyrosine kinase inhibitor axitinib has superior efficacy to sorafenib, the prior standard of care.⁹ Our patient noted that the cutaneous mRCC lesion seemed to be improving after starting treatment with axitinib 2 months prior to presentation. In addition to systemic chemotherapy, the surgical removal of lesions often is indicated for the treatment of cutaneous mRCC.^5,10 Our patient has continued axitinib and is doing well.

The Diagnosis: Metastatic Renal Cell Carcinoma

A shave biopsy of the right occipital scalp lesion demonstrated large clear cells arranged in oval nests with mildly atypical central nuclei (Figure). The findings were consistent with the clear cell type of metastatic renal cell carcinoma (mRCC) with tumor involvement in the deep margin. PAX8 immunostain was positive in the tumor, further supporting the diagnosis of mRCC.

The most common patient demographic diagnosed with renal cell carcinoma (RCC) is men in the sixth and seventh decades of life.^1,2 The classic presentation of RCC includes the triad of flank pain, hematuria, and a palpable abdominal mass. Other symptoms may include fatigue, weight loss, and anemia; however, small localized tumors rarely are symptomatic, and less than 10% of patients with RCC present with this classic triad.³ Many RCCs are diagnosed from incidental findings on abdominal imaging or from the presentation of metastatic disease.^1,2 The lungs, bones, and liver are the most common sites of metastases, while skin metastases are rare.² One study found only 3.3% (10/306) of RCC cases had cutaneous metastases and the scalp was the most common location. In half of these patients, the skin metastases were present at initial RCC diagnosis.⁴

The most common presentation of a cutaneous metastasis of RCC entails the rapid development of a reddish blue nodule on the face or scalp.^4,5 The differential diagnosis may include basal cell carcinoma, hemangioma, cutaneous angiosarcoma, pyogenic granuloma, and atypical fibroxanthoma. Careful elicitation of a medical history indicating any of the classic or systemic signs associated with RCC or a personal history of RCC should raise the suspicion for mRCC and prompt a biopsy.

Clear cell RCC is the most common type of primary RCC and 81% of mRCCs were found to be of the clear cell type. Clear cell RCC classically exhibits clear ballooned cytoplasm with distinct cell borders.⁶ Immunohistochemistry stains with PAX2 and PAX8 are helpful in diagnosing the renal origin of the metastatic tissue, with PAX8 being especially helpful (89% sensitivity).⁷

The von Hippel-Lindau gene, VHL, is involved in up to 60% of sporadic clear cell RCC cases, in addition to its involvement in VHL syndrome.1 von Hippel-Lindau syndrome is associated with clear cell RCC, retinal angiomas, hemangioblastomas of the central nervous system, and pheochromocytomas.¹ The mutated VHL gene is associated with an increased expression of vascular endothelial growth factor (VEGF), which promotes angiogenesis, endothelial mutagenesis, and vascular permeability.⁸ These physiologic responses are likely responsible for the proliferation and dissemination of neoplastic cells in clear cell RCC.⁹ The understanding of this pathogenic mechanism has led to the development of targeted effective treatments in RCC.

Systemic treatments for mRCC are rapidly evolving and improving.⁹ Vascular endothelial growth factor tyrosine kinase inhibitors such as sorafenib, sunitinib, and pazopanib, as well as the VEGF monoclonal antibody bevacizumab, have all demonstrated notable efficacy in the treatment of RCC. Phase 3 clinical trials for the treatment of mRCC have demonstrated that the new, more biochemically potent VEGF tyrosine kinase inhibitor axitinib has superior efficacy to sorafenib, the prior standard of care.⁹ Our patient noted that the cutaneous mRCC lesion seemed to be improving after starting treatment with axitinib 2 months prior to presentation. In addition to systemic chemotherapy, the surgical removal of lesions often is indicated for the treatment of cutaneous mRCC.^5,10 Our patient has continued axitinib and is doing well.

Q1: Answer: C

Cystoisospora belli (formerly known as Isospora belli) is a gastrointestinal protozoan. In patients with AIDS and other immunodeficiencies, it is an opportunistic pathogen that can cause watery diarrhea and weight loss. Infections are acquired by the ingestion of sporulated oocysts from food or water contaminated with human feces. In general, protozoal infections do not cause peripheral or tissue eosinophilia; however, Cystoisospora infection is an exception to this rule.

Diarrhea and peripheral eosinophilia in an immunocompromised individual should raise concern for Cystoisospora infection. The other protozoal infections listed can cause diarrhea, but do not cause eosinophilia.

Reference

1. Goodgame, R.W. Understanding intestinal spore-forming protozoa: Cryptosporidia, microsporidia, isospora, and cyclospora. Ann Intern Med. 1996;124:429-41.

Q1: Answer: C

Cystoisospora belli (formerly known as Isospora belli) is a gastrointestinal protozoan. In patients with AIDS and other immunodeficiencies, it is an opportunistic pathogen that can cause watery diarrhea and weight loss. Infections are acquired by the ingestion of sporulated oocysts from food or water contaminated with human feces. In general, protozoal infections do not cause peripheral or tissue eosinophilia; however, Cystoisospora infection is an exception to this rule.

Diarrhea and peripheral eosinophilia in an immunocompromised individual should raise concern for Cystoisospora infection. The other protozoal infections listed can cause diarrhea, but do not cause eosinophilia.

Reference

1. Goodgame, R.W. Understanding intestinal spore-forming protozoa: Cryptosporidia, microsporidia, isospora, and cyclospora. Ann Intern Med. 1996;124:429-41.

Q1: Answer: C

Cystoisospora belli (formerly known as Isospora belli) is a gastrointestinal protozoan. In patients with AIDS and other immunodeficiencies, it is an opportunistic pathogen that can cause watery diarrhea and weight loss. Infections are acquired by the ingestion of sporulated oocysts from food or water contaminated with human feces. In general, protozoal infections do not cause peripheral or tissue eosinophilia; however, Cystoisospora infection is an exception to this rule.

Diarrhea and peripheral eosinophilia in an immunocompromised individual should raise concern for Cystoisospora infection. The other protozoal infections listed can cause diarrhea, but do not cause eosinophilia.

Reference

1. Goodgame, R.W. Understanding intestinal spore-forming protozoa: Cryptosporidia, microsporidia, isospora, and cyclospora. Ann Intern Med. 1996;124:429-41.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.¹ Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.¹² Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.^1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.¹³ In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.¹³ Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.² Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.^2,3 Ustekinumab, however, has the major drawback of high cost.¹² Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.^14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.¹⁴

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.¹⁶ As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.¹⁶ After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.