Researchers have proposed the term “congenital Zika syndrome” to cover the range of severe damage and developmental abnormalities – including microcephaly – caused by Zika virus infection.

In the Oct. 3 online edition of JAMA Neurology, Adriana Suely de Oliveira Melo, MD, PhD, of the Instituto de Pesquisa Professor Amorim Neto in Campina Grande, Brazil, and her coauthors report on 11 babies with congenital Zika virus infection who were followed from gestation to 6 months of age.

©Devonyu/Thinkstock

Researchers have proposed the term “congenital Zika syndrome” to cover the range of severe damage and developmental abnormalities – including microcephaly – caused by Zika virus infection.

In the Oct. 3 online edition of JAMA Neurology, Adriana Suely de Oliveira Melo, MD, PhD, of the Instituto de Pesquisa Professor Amorim Neto in Campina Grande, Brazil, and her coauthors report on 11 babies with congenital Zika virus infection who were followed from gestation to 6 months of age.

©Devonyu/Thinkstock

Researchers have proposed the term “congenital Zika syndrome” to cover the range of severe damage and developmental abnormalities – including microcephaly – caused by Zika virus infection.

In the Oct. 3 online edition of JAMA Neurology, Adriana Suely de Oliveira Melo, MD, PhD, of the Instituto de Pesquisa Professor Amorim Neto in Campina Grande, Brazil, and her coauthors report on 11 babies with congenital Zika virus infection who were followed from gestation to 6 months of age.

©Devonyu/Thinkstock

Rosacea is a chronic inflammatory disorder that may negatively impact patients’ quality of life (QOL).^1,2 Papulopustular rosacea (PPR) is characterized by centrofacial inflammatory lesions and erythema as well as burning and stinging secondary to skin barrier dysfunction.^3-5 Increasing rosacea severity is associated with greater rates of anxiety and depression and lower QOL⁶ as well as low self-esteem and feelings of embarrassment.^7,8 Accordingly, assessing patient perceptions of rosacea treatments is necessary for understanding its impact on patient health.^6,9

The Rosacea International Expert Group has emphasized the need to incorporate patient assessments of disease severity and QOL when developing therapeutic strategies for rosacea.⁷ Ease of use, sensory experience, and patient preference also are important dimensions in the evaluation of topical medications, as attributes of specific formulations may affect usability, adherence, and efficacy.^10,11

An azelaic acid (AzA) 15% foam formulation, which was approved by the US Food and Drug Administration in 2015, was developed to deliver AzA in a vehicle designed to improve treatment experience in patients with mild to moderate PPR.¹² Results from a clinical trial demonstrated superiority of AzA foam to vehicle foam for primary end points that included therapeutic success rate and change in inflammatory lesion count.^13,14 Secondary end points assessed in the current analysis included patient perception of product usability, efficacy, and effect on QOL. These patient-reported outcome (PRO) results are reported here.

Methods

Study Design

The design of this phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was described in more detail in an earlier report.¹³ This study was approved by all appropriate institutional review boards. Eligible participants were 18 years and older with moderate or severe PPR, 12 to 50 inflammatory lesions, and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication (0.5 g) or vehicle foam was applied twice daily to the entire face until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to investigator global assessment and nominal change in inflammatory lesion count—were previously reported,¹³ as well as secondary efficacy outcomes including change in inflammatory lesion count, therapeutic response rate, and change in erythema rating.¹⁴

Patient-Reported Secondary Efficacy Outcomes

The secondary PRO end points were patient-reported global assessment of treatment response (rated as excellent, good, fair, none, or worse), global assessment of tolerability (rated as excellent, good, acceptable despite minor irritation, less acceptable due to continuous irritation, not acceptable, or no opinion), and opinion on cosmetic acceptability and practicability of product use in areas adjacent to the hairline (rated as very good, good, satisfactory, poor, or no opinion).

Additionally, QOL was measured by 3 validated standardized PRO tools, including the Rosacea Quality of Life Index (RosaQOL),¹⁵ the EuroQOL 5-dimension 5-level questionnaire (EQ-5D-5L),¹⁶ and the Dermatology Life Quality Index (DLQI). The RosaQOL is a rosacea-specific instrument assessing 3 constructs: (1) symptom, (2) emotion, and (3) function. The EQ-5D-5L questionnaire measures overall health status and comprises 5 constructs: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort, and (5) anxiety/depression. The DLQI is a general, dermatology-oriented instrument categorized into 6 constructs: (1) symptoms and feelings, (2) daily activities, (3) leisure, (4) work and school, (5) personal relationships, and (6) treatment.

Statistical Analyses

Patient-reported outcomes were analyzed in an exploratory manner and evaluated at EoT relative to baseline. Self-reported global assessment of treatment response and change in RosaQOL, EQ-5D-5L, and DLQI scores between AzA foam and vehicle foam groups were evaluated using the Wilcoxon rank sum test. Categorical change in the number of participants achieving an increase of 5 or more points in overall DLQI score was evaluated using a χ² test.

Safety

Safety was analyzed for all randomized patients who were dispensed any study medication. All analyses were performed using SAS version 9.2.

Results

Of the 961 participants included in the study, 483 were randomized to receive AzA foam and 478 were randomized to receive vehicle foam. The mean age was 51.5 years, and the majority of participants were female (73.0%) and white (95.5%)(Table). At baseline, 834 (86.8%) participants had moderate PPR and 127 (13.2%) had severe PPR. The mean inflammatory lesion count (SD) was 21.4 (8.9). No significant differences in baseline characteristics were observed between treatment groups.

Patient-reported global assessment of treatment response differed between treatment groups at EoT (P<.001)(Figure 1). Higher ratings of treatment response were reported among the AzA foam group (excellent, 17.2%; good, 40.0%) versus vehicle foam (excellent, 9.7%; good, 35.0%). The number of participants reporting no treatment response was 13.1% in the AzA foam group, with 1.8% reporting worsening of their condition, while 19.4% of participants in the vehicle foam group reported no response, with 6.3% reporting worsening of their condition (Figure 1).

The incidence of drug-related adverse events (AEs) was greater in the AzA foam group versus the vehicle foam group (7.7% vs 4.8%). Drug-related AEs occurring in 1% of the AzA foam group were application-site pain including tenderness, stinging, and burning (3.5% for AzA foam vs 1.3% for vehicle foam); application-site pruritus (1.4% vs 0.4%); and application-site dryness (1.0% vs 0.6%). One drug-related AE of severe intensity—application-site dermatitis—occurred in the vehicle foam group; all other drug-related AEs were mild or moderate.¹⁴ More detailed safety results are described in a previous report.¹³

Comment

The PRO outcome data reported here are consistent with previously reported statistically significant improvements in investigator-assessed primary end points for the treatment of PPR with AzA foam.^13,14 The data demonstrate that AzA foam benefits both clinical and patient-oriented dimensions of rosacea disease burden and suggest an association between positive treatment response and improved QOL.

Specifically, patient evaluation of treatment response to AzA foam was highly favorable, with 57.2% reporting excellent or good response and 85.1% reporting positive response overall. Recognizing the relapsing-remitting course of PPR, only 1.8% of the AzA foam group experienced worsening of disease at EoT.

The DLQI and RosaQOL instruments revealed notable improvements in QOL from baseline for both treatment groups. Although no significant differences in RosaQOL scores were observed between groups at EoT, significant differences in DLQI scores were detected. Almost one-quarter of participants in the AzA foam group achieved at least a 5-point improvement in DLQI score, exceeding the 4-point threshold for clinically meaningful change.¹⁷ Although little change in EQ-5D-5L scores was observed at EoT for both groups with no between-group differences, this finding is not unexpected, as this instrument assesses QOL dimensions such as loss of function, mobility, and ability to wash or dress, which are unlikely to be compromised in most rosacea patients.

Our results also underscore the importance of vehicle in the treatment of compromised skin. Studies of topical treatments for other dermatoses suggest that vehicle properties may reduce disease severity and improve QOL independent of active ingredients.^10,18 For example, ease of application, minimal residue, and less time spent in application may explain the superiority of foam to other vehicles in the treatment of psoriasis.¹⁸ Our data demonstrating high cosmetic favorability of AzA foam are consistent with these prior observations. Increased tolerability of foam formulations also may affect response to treatment, in part by supporting adherence.¹⁸ Most participants receiving AzA foam described tolerability as excellent or good, and the discontinuation rate was low (1.2% of participants in the AzA foam group left the study due to AEs) in the setting of near-complete dosage administration (97% of expected doses applied).¹³

Conclusion

These results indicate that use of AzA foam as well as its novel vehicle results in high patient satisfaction and improved QOL. Although additional research is necessary to further delineate the relationship between PROs and other measures of clinical efficacy, our data demonstrate a positive treatment experience as perceived by patients that parallels the clinical efficacy of AzA foam for the treatment of PPR.^13,14

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

Rosacea is a chronic inflammatory disorder that may negatively impact patients’ quality of life (QOL).^1,2 Papulopustular rosacea (PPR) is characterized by centrofacial inflammatory lesions and erythema as well as burning and stinging secondary to skin barrier dysfunction.^3-5 Increasing rosacea severity is associated with greater rates of anxiety and depression and lower QOL⁶ as well as low self-esteem and feelings of embarrassment.^7,8 Accordingly, assessing patient perceptions of rosacea treatments is necessary for understanding its impact on patient health.^6,9

The Rosacea International Expert Group has emphasized the need to incorporate patient assessments of disease severity and QOL when developing therapeutic strategies for rosacea.⁷ Ease of use, sensory experience, and patient preference also are important dimensions in the evaluation of topical medications, as attributes of specific formulations may affect usability, adherence, and efficacy.^10,11

An azelaic acid (AzA) 15% foam formulation, which was approved by the US Food and Drug Administration in 2015, was developed to deliver AzA in a vehicle designed to improve treatment experience in patients with mild to moderate PPR.¹² Results from a clinical trial demonstrated superiority of AzA foam to vehicle foam for primary end points that included therapeutic success rate and change in inflammatory lesion count.^13,14 Secondary end points assessed in the current analysis included patient perception of product usability, efficacy, and effect on QOL. These patient-reported outcome (PRO) results are reported here.

Methods

Study Design

The design of this phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was described in more detail in an earlier report.¹³ This study was approved by all appropriate institutional review boards. Eligible participants were 18 years and older with moderate or severe PPR, 12 to 50 inflammatory lesions, and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication (0.5 g) or vehicle foam was applied twice daily to the entire face until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to investigator global assessment and nominal change in inflammatory lesion count—were previously reported,¹³ as well as secondary efficacy outcomes including change in inflammatory lesion count, therapeutic response rate, and change in erythema rating.¹⁴

Patient-Reported Secondary Efficacy Outcomes

The secondary PRO end points were patient-reported global assessment of treatment response (rated as excellent, good, fair, none, or worse), global assessment of tolerability (rated as excellent, good, acceptable despite minor irritation, less acceptable due to continuous irritation, not acceptable, or no opinion), and opinion on cosmetic acceptability and practicability of product use in areas adjacent to the hairline (rated as very good, good, satisfactory, poor, or no opinion).

Additionally, QOL was measured by 3 validated standardized PRO tools, including the Rosacea Quality of Life Index (RosaQOL),¹⁵ the EuroQOL 5-dimension 5-level questionnaire (EQ-5D-5L),¹⁶ and the Dermatology Life Quality Index (DLQI). The RosaQOL is a rosacea-specific instrument assessing 3 constructs: (1) symptom, (2) emotion, and (3) function. The EQ-5D-5L questionnaire measures overall health status and comprises 5 constructs: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort, and (5) anxiety/depression. The DLQI is a general, dermatology-oriented instrument categorized into 6 constructs: (1) symptoms and feelings, (2) daily activities, (3) leisure, (4) work and school, (5) personal relationships, and (6) treatment.

Statistical Analyses

Patient-reported outcomes were analyzed in an exploratory manner and evaluated at EoT relative to baseline. Self-reported global assessment of treatment response and change in RosaQOL, EQ-5D-5L, and DLQI scores between AzA foam and vehicle foam groups were evaluated using the Wilcoxon rank sum test. Categorical change in the number of participants achieving an increase of 5 or more points in overall DLQI score was evaluated using a χ² test.

Safety

Safety was analyzed for all randomized patients who were dispensed any study medication. All analyses were performed using SAS version 9.2.

Results

Of the 961 participants included in the study, 483 were randomized to receive AzA foam and 478 were randomized to receive vehicle foam. The mean age was 51.5 years, and the majority of participants were female (73.0%) and white (95.5%)(Table). At baseline, 834 (86.8%) participants had moderate PPR and 127 (13.2%) had severe PPR. The mean inflammatory lesion count (SD) was 21.4 (8.9). No significant differences in baseline characteristics were observed between treatment groups.

Patient-reported global assessment of treatment response differed between treatment groups at EoT (P<.001)(Figure 1). Higher ratings of treatment response were reported among the AzA foam group (excellent, 17.2%; good, 40.0%) versus vehicle foam (excellent, 9.7%; good, 35.0%). The number of participants reporting no treatment response was 13.1% in the AzA foam group, with 1.8% reporting worsening of their condition, while 19.4% of participants in the vehicle foam group reported no response, with 6.3% reporting worsening of their condition (Figure 1).

The incidence of drug-related adverse events (AEs) was greater in the AzA foam group versus the vehicle foam group (7.7% vs 4.8%). Drug-related AEs occurring in 1% of the AzA foam group were application-site pain including tenderness, stinging, and burning (3.5% for AzA foam vs 1.3% for vehicle foam); application-site pruritus (1.4% vs 0.4%); and application-site dryness (1.0% vs 0.6%). One drug-related AE of severe intensity—application-site dermatitis—occurred in the vehicle foam group; all other drug-related AEs were mild or moderate.¹⁴ More detailed safety results are described in a previous report.¹³

Comment

The PRO outcome data reported here are consistent with previously reported statistically significant improvements in investigator-assessed primary end points for the treatment of PPR with AzA foam.^13,14 The data demonstrate that AzA foam benefits both clinical and patient-oriented dimensions of rosacea disease burden and suggest an association between positive treatment response and improved QOL.

Specifically, patient evaluation of treatment response to AzA foam was highly favorable, with 57.2% reporting excellent or good response and 85.1% reporting positive response overall. Recognizing the relapsing-remitting course of PPR, only 1.8% of the AzA foam group experienced worsening of disease at EoT.

The DLQI and RosaQOL instruments revealed notable improvements in QOL from baseline for both treatment groups. Although no significant differences in RosaQOL scores were observed between groups at EoT, significant differences in DLQI scores were detected. Almost one-quarter of participants in the AzA foam group achieved at least a 5-point improvement in DLQI score, exceeding the 4-point threshold for clinically meaningful change.¹⁷ Although little change in EQ-5D-5L scores was observed at EoT for both groups with no between-group differences, this finding is not unexpected, as this instrument assesses QOL dimensions such as loss of function, mobility, and ability to wash or dress, which are unlikely to be compromised in most rosacea patients.

Our results also underscore the importance of vehicle in the treatment of compromised skin. Studies of topical treatments for other dermatoses suggest that vehicle properties may reduce disease severity and improve QOL independent of active ingredients.^10,18 For example, ease of application, minimal residue, and less time spent in application may explain the superiority of foam to other vehicles in the treatment of psoriasis.¹⁸ Our data demonstrating high cosmetic favorability of AzA foam are consistent with these prior observations. Increased tolerability of foam formulations also may affect response to treatment, in part by supporting adherence.¹⁸ Most participants receiving AzA foam described tolerability as excellent or good, and the discontinuation rate was low (1.2% of participants in the AzA foam group left the study due to AEs) in the setting of near-complete dosage administration (97% of expected doses applied).¹³

Conclusion

These results indicate that use of AzA foam as well as its novel vehicle results in high patient satisfaction and improved QOL. Although additional research is necessary to further delineate the relationship between PROs and other measures of clinical efficacy, our data demonstrate a positive treatment experience as perceived by patients that parallels the clinical efficacy of AzA foam for the treatment of PPR.^13,14

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

Rosacea is a chronic inflammatory disorder that may negatively impact patients’ quality of life (QOL).^1,2 Papulopustular rosacea (PPR) is characterized by centrofacial inflammatory lesions and erythema as well as burning and stinging secondary to skin barrier dysfunction.^3-5 Increasing rosacea severity is associated with greater rates of anxiety and depression and lower QOL⁶ as well as low self-esteem and feelings of embarrassment.^7,8 Accordingly, assessing patient perceptions of rosacea treatments is necessary for understanding its impact on patient health.^6,9

The Rosacea International Expert Group has emphasized the need to incorporate patient assessments of disease severity and QOL when developing therapeutic strategies for rosacea.⁷ Ease of use, sensory experience, and patient preference also are important dimensions in the evaluation of topical medications, as attributes of specific formulations may affect usability, adherence, and efficacy.^10,11

An azelaic acid (AzA) 15% foam formulation, which was approved by the US Food and Drug Administration in 2015, was developed to deliver AzA in a vehicle designed to improve treatment experience in patients with mild to moderate PPR.¹² Results from a clinical trial demonstrated superiority of AzA foam to vehicle foam for primary end points that included therapeutic success rate and change in inflammatory lesion count.^13,14 Secondary end points assessed in the current analysis included patient perception of product usability, efficacy, and effect on QOL. These patient-reported outcome (PRO) results are reported here.

Methods

Study Design

The design of this phase 3 multicenter, randomized, double-blind, vehicle-controlled, parallel-group clinical trial was described in more detail in an earlier report.¹³ This study was approved by all appropriate institutional review boards. Eligible participants were 18 years and older with moderate or severe PPR, 12 to 50 inflammatory lesions, and persistent erythema with or without telangiectasia. Exclusion criteria included known nonresponse to AzA, current or prior use (within 6 weeks of randomization) of noninvestigational products to treat rosacea, and presence of other dermatoses that could interfere with rosacea evaluation.

Participants were randomized into the AzA foam or vehicle group (1:1 ratio). The study medication (0.5 g) or vehicle foam was applied twice daily to the entire face until the end of treatment (EoT) at 12 weeks. Efficacy and safety parameters were evaluated at baseline and at 4, 8, and 12 weeks of treatment, and at a follow-up visit 4 weeks after EoT (week 16).

Results for the coprimary efficacy end points—therapeutic success rate according to investigator global assessment and nominal change in inflammatory lesion count—were previously reported,¹³ as well as secondary efficacy outcomes including change in inflammatory lesion count, therapeutic response rate, and change in erythema rating.¹⁴

Patient-Reported Secondary Efficacy Outcomes

The secondary PRO end points were patient-reported global assessment of treatment response (rated as excellent, good, fair, none, or worse), global assessment of tolerability (rated as excellent, good, acceptable despite minor irritation, less acceptable due to continuous irritation, not acceptable, or no opinion), and opinion on cosmetic acceptability and practicability of product use in areas adjacent to the hairline (rated as very good, good, satisfactory, poor, or no opinion).

Additionally, QOL was measured by 3 validated standardized PRO tools, including the Rosacea Quality of Life Index (RosaQOL),¹⁵ the EuroQOL 5-dimension 5-level questionnaire (EQ-5D-5L),¹⁶ and the Dermatology Life Quality Index (DLQI). The RosaQOL is a rosacea-specific instrument assessing 3 constructs: (1) symptom, (2) emotion, and (3) function. The EQ-5D-5L questionnaire measures overall health status and comprises 5 constructs: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort, and (5) anxiety/depression. The DLQI is a general, dermatology-oriented instrument categorized into 6 constructs: (1) symptoms and feelings, (2) daily activities, (3) leisure, (4) work and school, (5) personal relationships, and (6) treatment.

Statistical Analyses

Patient-reported outcomes were analyzed in an exploratory manner and evaluated at EoT relative to baseline. Self-reported global assessment of treatment response and change in RosaQOL, EQ-5D-5L, and DLQI scores between AzA foam and vehicle foam groups were evaluated using the Wilcoxon rank sum test. Categorical change in the number of participants achieving an increase of 5 or more points in overall DLQI score was evaluated using a χ² test.

Safety

Safety was analyzed for all randomized patients who were dispensed any study medication. All analyses were performed using SAS version 9.2.

Results

Of the 961 participants included in the study, 483 were randomized to receive AzA foam and 478 were randomized to receive vehicle foam. The mean age was 51.5 years, and the majority of participants were female (73.0%) and white (95.5%)(Table). At baseline, 834 (86.8%) participants had moderate PPR and 127 (13.2%) had severe PPR. The mean inflammatory lesion count (SD) was 21.4 (8.9). No significant differences in baseline characteristics were observed between treatment groups.

Patient-reported global assessment of treatment response differed between treatment groups at EoT (P<.001)(Figure 1). Higher ratings of treatment response were reported among the AzA foam group (excellent, 17.2%; good, 40.0%) versus vehicle foam (excellent, 9.7%; good, 35.0%). The number of participants reporting no treatment response was 13.1% in the AzA foam group, with 1.8% reporting worsening of their condition, while 19.4% of participants in the vehicle foam group reported no response, with 6.3% reporting worsening of their condition (Figure 1).

The incidence of drug-related adverse events (AEs) was greater in the AzA foam group versus the vehicle foam group (7.7% vs 4.8%). Drug-related AEs occurring in 1% of the AzA foam group were application-site pain including tenderness, stinging, and burning (3.5% for AzA foam vs 1.3% for vehicle foam); application-site pruritus (1.4% vs 0.4%); and application-site dryness (1.0% vs 0.6%). One drug-related AE of severe intensity—application-site dermatitis—occurred in the vehicle foam group; all other drug-related AEs were mild or moderate.¹⁴ More detailed safety results are described in a previous report.¹³

Comment

The PRO outcome data reported here are consistent with previously reported statistically significant improvements in investigator-assessed primary end points for the treatment of PPR with AzA foam.^13,14 The data demonstrate that AzA foam benefits both clinical and patient-oriented dimensions of rosacea disease burden and suggest an association between positive treatment response and improved QOL.

Specifically, patient evaluation of treatment response to AzA foam was highly favorable, with 57.2% reporting excellent or good response and 85.1% reporting positive response overall. Recognizing the relapsing-remitting course of PPR, only 1.8% of the AzA foam group experienced worsening of disease at EoT.

The DLQI and RosaQOL instruments revealed notable improvements in QOL from baseline for both treatment groups. Although no significant differences in RosaQOL scores were observed between groups at EoT, significant differences in DLQI scores were detected. Almost one-quarter of participants in the AzA foam group achieved at least a 5-point improvement in DLQI score, exceeding the 4-point threshold for clinically meaningful change.¹⁷ Although little change in EQ-5D-5L scores was observed at EoT for both groups with no between-group differences, this finding is not unexpected, as this instrument assesses QOL dimensions such as loss of function, mobility, and ability to wash or dress, which are unlikely to be compromised in most rosacea patients.

Our results also underscore the importance of vehicle in the treatment of compromised skin. Studies of topical treatments for other dermatoses suggest that vehicle properties may reduce disease severity and improve QOL independent of active ingredients.^10,18 For example, ease of application, minimal residue, and less time spent in application may explain the superiority of foam to other vehicles in the treatment of psoriasis.¹⁸ Our data demonstrating high cosmetic favorability of AzA foam are consistent with these prior observations. Increased tolerability of foam formulations also may affect response to treatment, in part by supporting adherence.¹⁸ Most participants receiving AzA foam described tolerability as excellent or good, and the discontinuation rate was low (1.2% of participants in the AzA foam group left the study due to AEs) in the setting of near-complete dosage administration (97% of expected doses applied).¹³

Conclusion

These results indicate that use of AzA foam as well as its novel vehicle results in high patient satisfaction and improved QOL. Although additional research is necessary to further delineate the relationship between PROs and other measures of clinical efficacy, our data demonstrate a positive treatment experience as perceived by patients that parallels the clinical efficacy of AzA foam for the treatment of PPR.^13,14

Acknowledgment

Editorial support through inVentiv Medical Communications (New York, New York) was provided by Bayer Pharmaceuticals.

BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.

Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.

Courtesy ASTRO

BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.

Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.

Courtesy ASTRO

BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.

Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.

Courtesy ASTRO

Folliculotropic Mycosis Fungoides

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that occurs mostly in adults with a male predilection. The disease clinically favors the head and neck. Patients commonly present with pruritic papules that often are grouped, alopecia, and frequent secondary bacterial infections. Less commonly patients present with acneiform lesions and mucinorrhea. Patients often experience more pruritus in FMF than in classic MF, which can provide a good means of assessing disease activity. Disease-specific 5-year survival is approximately 70% to 80%, which is worse than classic plaque-stage MF and similar to tumor-stage MF.¹

Treatment of FMF differs from classic MF in that the lesions are less responsive to skin-targeted therapies due to the perifollicular nature of dermal infiltrates. Superficial skin lesions can be treated with psoralen plus UVA (PUVA) therapy. Other options include PUVA in combination with interferon alfa or retinoids and local radiotherapy for solitary thick tumors; however, in patients who have more infiltrative skin lesions or had PUVA therapy that failed, total skin electron beam therapy may be required.²

On histologic examination, there typically is perivascular and periadnexal localization of dermal infiltrates with varied involvement of the follicular epithelium and damage to hair follicles by atypical small, medium, and large hyperchromatic lymphocytes with cerebriform nuclei. Mucinous degeneration of the follicular epithelium can be seen, as highlighted on Alcian blue staining, and a mixed infiltrate of eosinophils and plasma cells often is present (quiz image and Figure 1). Frequent sparing of the epidermis is noteworthy.^2-4 In most cases, the neoplastic T lymphocytes are characterized by a CD3⁺CD4⁺CD8^-immunophenotype as is seen in classic MF. Sometimes an admixture of CD30⁺ blast cells is seen.¹

Histologic differential considerations for FMF include eosinophilic pustular folliculitis (EPF), primary follicular mucinosis, lupus erythematosus, and pityrosporum folliculitis.

Eosinophilic pustular folliculitis has several clinical subtypes, such as classic Ofuji disease and immunosuppression-associated EPF secondary to human immunodeficiency virus. Histologically, EPF is characterized by spongiosis of the hair follicle epithelium with exocytosis of a mixed infiltrate of lymphocytes and eosinophils extending from the sebaceous gland and its duct to the infundibulum with formation of hallmark eosinophilic pustules (Figure 2). Infiltration of neutrophils in inflamed lesions generally is seen. Eosinophilic pustular folliculitis is an important differential for FMF, as follicular mucinosis has been observed in lesions of EPF.⁵ Both EPF and FMF can exhibit eosinophils and lymphocytes in the upper dermis, spongiosis of the hair follicle epithelium, and mucinous degeneration of follicles,⁶ though lymphocytic atypia and relatively fewer eosinophils are suggestive of the latter.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Primary follicular mucinosis (PFM) tends to occur as a solitary lesion in younger female patients in contrast to the multiple lesions that typically appear in older male patients with FMF. Histologically, PFM usually manifests as large, cystic, mucin-filled spaces and polyclonal perivascular and periadnexal lymphocytic infiltrate without notable cellular atypia or epidermotropism (Figure 3). Because follicular mucinosis is a common feature of FMF, its distinction from PFM can be challenging and often is aided by the absence of cellular atypia and relatively mild lymphocytic infiltrate in the latter.⁷

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Cutaneous lupus erythematosus with its characteristic folliculocentric lymphocytic infiltration and associated dermal mucin also qualifies as a potential differential possibility for FMF; however, the perivascular and periadnexal pattern of lymphocytic infiltration as well as the localization of mucin to the reticular dermal interstitium^8,9 are key histopathologic distinctions (Figure 4). Furthermore, although the histologic presentation of lupus erythematosus can be variable, it also classically shows interface dermatitis, basement membrane thickening, and follicular plugging.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Pityrosporum folliculitis is the most common cause of fungal folliculitis and is caused by the Malassezia species. On histology, there typically is an unremarkable epithelium with plugged follicles and suppurative folliculitis. Serial sections of the biopsy specimen often are required to identify dilated, follicle-containing, budding yeast cells (Figure 5). Organisms are located predominantly within the infundibulum and orifice of follicular lumen, are positive for periodic acid-Schiff, and are diastase resistant.¹⁰

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Folliculotropic Mycosis Fungoides

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that occurs mostly in adults with a male predilection. The disease clinically favors the head and neck. Patients commonly present with pruritic papules that often are grouped, alopecia, and frequent secondary bacterial infections. Less commonly patients present with acneiform lesions and mucinorrhea. Patients often experience more pruritus in FMF than in classic MF, which can provide a good means of assessing disease activity. Disease-specific 5-year survival is approximately 70% to 80%, which is worse than classic plaque-stage MF and similar to tumor-stage MF.¹

Treatment of FMF differs from classic MF in that the lesions are less responsive to skin-targeted therapies due to the perifollicular nature of dermal infiltrates. Superficial skin lesions can be treated with psoralen plus UVA (PUVA) therapy. Other options include PUVA in combination with interferon alfa or retinoids and local radiotherapy for solitary thick tumors; however, in patients who have more infiltrative skin lesions or had PUVA therapy that failed, total skin electron beam therapy may be required.²

On histologic examination, there typically is perivascular and periadnexal localization of dermal infiltrates with varied involvement of the follicular epithelium and damage to hair follicles by atypical small, medium, and large hyperchromatic lymphocytes with cerebriform nuclei. Mucinous degeneration of the follicular epithelium can be seen, as highlighted on Alcian blue staining, and a mixed infiltrate of eosinophils and plasma cells often is present (quiz image and Figure 1). Frequent sparing of the epidermis is noteworthy.^2-4 In most cases, the neoplastic T lymphocytes are characterized by a CD3⁺CD4⁺CD8^-immunophenotype as is seen in classic MF. Sometimes an admixture of CD30⁺ blast cells is seen.¹

Histologic differential considerations for FMF include eosinophilic pustular folliculitis (EPF), primary follicular mucinosis, lupus erythematosus, and pityrosporum folliculitis.

Eosinophilic pustular folliculitis has several clinical subtypes, such as classic Ofuji disease and immunosuppression-associated EPF secondary to human immunodeficiency virus. Histologically, EPF is characterized by spongiosis of the hair follicle epithelium with exocytosis of a mixed infiltrate of lymphocytes and eosinophils extending from the sebaceous gland and its duct to the infundibulum with formation of hallmark eosinophilic pustules (Figure 2). Infiltration of neutrophils in inflamed lesions generally is seen. Eosinophilic pustular folliculitis is an important differential for FMF, as follicular mucinosis has been observed in lesions of EPF.⁵ Both EPF and FMF can exhibit eosinophils and lymphocytes in the upper dermis, spongiosis of the hair follicle epithelium, and mucinous degeneration of follicles,⁶ though lymphocytic atypia and relatively fewer eosinophils are suggestive of the latter.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Primary follicular mucinosis (PFM) tends to occur as a solitary lesion in younger female patients in contrast to the multiple lesions that typically appear in older male patients with FMF. Histologically, PFM usually manifests as large, cystic, mucin-filled spaces and polyclonal perivascular and periadnexal lymphocytic infiltrate without notable cellular atypia or epidermotropism (Figure 3). Because follicular mucinosis is a common feature of FMF, its distinction from PFM can be challenging and often is aided by the absence of cellular atypia and relatively mild lymphocytic infiltrate in the latter.⁷

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Cutaneous lupus erythematosus with its characteristic folliculocentric lymphocytic infiltration and associated dermal mucin also qualifies as a potential differential possibility for FMF; however, the perivascular and periadnexal pattern of lymphocytic infiltration as well as the localization of mucin to the reticular dermal interstitium^8,9 are key histopathologic distinctions (Figure 4). Furthermore, although the histologic presentation of lupus erythematosus can be variable, it also classically shows interface dermatitis, basement membrane thickening, and follicular plugging.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Pityrosporum folliculitis is the most common cause of fungal folliculitis and is caused by the Malassezia species. On histology, there typically is an unremarkable epithelium with plugged follicles and suppurative folliculitis. Serial sections of the biopsy specimen often are required to identify dilated, follicle-containing, budding yeast cells (Figure 5). Organisms are located predominantly within the infundibulum and orifice of follicular lumen, are positive for periodic acid-Schiff, and are diastase resistant.¹⁰

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Folliculotropic Mycosis Fungoides

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that occurs mostly in adults with a male predilection. The disease clinically favors the head and neck. Patients commonly present with pruritic papules that often are grouped, alopecia, and frequent secondary bacterial infections. Less commonly patients present with acneiform lesions and mucinorrhea. Patients often experience more pruritus in FMF than in classic MF, which can provide a good means of assessing disease activity. Disease-specific 5-year survival is approximately 70% to 80%, which is worse than classic plaque-stage MF and similar to tumor-stage MF.¹

Treatment of FMF differs from classic MF in that the lesions are less responsive to skin-targeted therapies due to the perifollicular nature of dermal infiltrates. Superficial skin lesions can be treated with psoralen plus UVA (PUVA) therapy. Other options include PUVA in combination with interferon alfa or retinoids and local radiotherapy for solitary thick tumors; however, in patients who have more infiltrative skin lesions or had PUVA therapy that failed, total skin electron beam therapy may be required.²

On histologic examination, there typically is perivascular and periadnexal localization of dermal infiltrates with varied involvement of the follicular epithelium and damage to hair follicles by atypical small, medium, and large hyperchromatic lymphocytes with cerebriform nuclei. Mucinous degeneration of the follicular epithelium can be seen, as highlighted on Alcian blue staining, and a mixed infiltrate of eosinophils and plasma cells often is present (quiz image and Figure 1). Frequent sparing of the epidermis is noteworthy.^2-4 In most cases, the neoplastic T lymphocytes are characterized by a CD3⁺CD4⁺CD8^-immunophenotype as is seen in classic MF. Sometimes an admixture of CD30⁺ blast cells is seen.¹

Histologic differential considerations for FMF include eosinophilic pustular folliculitis (EPF), primary follicular mucinosis, lupus erythematosus, and pityrosporum folliculitis.

Eosinophilic pustular folliculitis has several clinical subtypes, such as classic Ofuji disease and immunosuppression-associated EPF secondary to human immunodeficiency virus. Histologically, EPF is characterized by spongiosis of the hair follicle epithelium with exocytosis of a mixed infiltrate of lymphocytes and eosinophils extending from the sebaceous gland and its duct to the infundibulum with formation of hallmark eosinophilic pustules (Figure 2). Infiltration of neutrophils in inflamed lesions generally is seen. Eosinophilic pustular folliculitis is an important differential for FMF, as follicular mucinosis has been observed in lesions of EPF.⁵ Both EPF and FMF can exhibit eosinophils and lymphocytes in the upper dermis, spongiosis of the hair follicle epithelium, and mucinous degeneration of follicles,⁶ though lymphocytic atypia and relatively fewer eosinophils are suggestive of the latter.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Primary follicular mucinosis (PFM) tends to occur as a solitary lesion in younger female patients in contrast to the multiple lesions that typically appear in older male patients with FMF. Histologically, PFM usually manifests as large, cystic, mucin-filled spaces and polyclonal perivascular and periadnexal lymphocytic infiltrate without notable cellular atypia or epidermotropism (Figure 3). Because follicular mucinosis is a common feature of FMF, its distinction from PFM can be challenging and often is aided by the absence of cellular atypia and relatively mild lymphocytic infiltrate in the latter.⁷

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Cutaneous lupus erythematosus with its characteristic folliculocentric lymphocytic infiltration and associated dermal mucin also qualifies as a potential differential possibility for FMF; however, the perivascular and periadnexal pattern of lymphocytic infiltration as well as the localization of mucin to the reticular dermal interstitium^8,9 are key histopathologic distinctions (Figure 4). Furthermore, although the histologic presentation of lupus erythematosus can be variable, it also classically shows interface dermatitis, basement membrane thickening, and follicular plugging.

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

Pityrosporum folliculitis is the most common cause of fungal folliculitis and is caused by the Malassezia species. On histology, there typically is an unremarkable epithelium with plugged follicles and suppurative folliculitis. Serial sections of the biopsy specimen often are required to identify dilated, follicle-containing, budding yeast cells (Figure 5). Organisms are located predominantly within the infundibulum and orifice of follicular lumen, are positive for periodic acid-Schiff, and are diastase resistant.¹⁰

Photograph courtesy of Brian Swick, MD (Iowa City, Iowa).

ROME – A newly validated, simplified algorithm for the management of patients with suspected acute pulmonary embolism enables physicians to safely exclude the disorder in roughly half of patients without resorting to CT pulmonary angiography, Tom van der Hulle, MD, reported at the annual congress of the European Society of Cardiology.

“This is the largest study ever performed in the diagnostic management of suspected pulmonary embolism. Based on our results, I think the YEARS algorithm is ready to be used in daily clinical practice,” declared Dr. van der Hulle of the department of thrombosis and hemostasis at Leiden (the Netherlands) University Medical Center.

Bruce Jancin/Frontline Medical News

[email protected]

ROME – A newly validated, simplified algorithm for the management of patients with suspected acute pulmonary embolism enables physicians to safely exclude the disorder in roughly half of patients without resorting to CT pulmonary angiography, Tom van der Hulle, MD, reported at the annual congress of the European Society of Cardiology.

“This is the largest study ever performed in the diagnostic management of suspected pulmonary embolism. Based on our results, I think the YEARS algorithm is ready to be used in daily clinical practice,” declared Dr. van der Hulle of the department of thrombosis and hemostasis at Leiden (the Netherlands) University Medical Center.

Bruce Jancin/Frontline Medical News

[email protected]

ROME – A newly validated, simplified algorithm for the management of patients with suspected acute pulmonary embolism enables physicians to safely exclude the disorder in roughly half of patients without resorting to CT pulmonary angiography, Tom van der Hulle, MD, reported at the annual congress of the European Society of Cardiology.

“This is the largest study ever performed in the diagnostic management of suspected pulmonary embolism. Based on our results, I think the YEARS algorithm is ready to be used in daily clinical practice,” declared Dr. van der Hulle of the department of thrombosis and hemostasis at Leiden (the Netherlands) University Medical Center.

Bruce Jancin/Frontline Medical News

[email protected]

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.¹ It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.² Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.^2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.^3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.^2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).⁵

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in –30°C freezers, making it one of the largest repositories in the world.^3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.⁷

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.⁴ The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.⁶ Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.^8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.⁸ Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.⁵

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.⁸ With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.⁸ However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.¹⁰ The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.^9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.^9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.¹ It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.² Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.^2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.^3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.^2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).⁵

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in –30°C freezers, making it one of the largest repositories in the world.^3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.⁷

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.⁴ The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.⁶ Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.^8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.⁸ Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.⁵

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.⁸ With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.⁸ However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.¹⁰ The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.^9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.^9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.¹ It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.² Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.^2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.^3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.^2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).⁵

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in –30°C freezers, making it one of the largest repositories in the world.^3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.⁷

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.⁴ The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.⁶ Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.^8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.⁸ Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.⁵

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.⁸ With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.⁸ However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.¹⁰ The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.^9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.^9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

DENVER – The malignancy risk of thyroid nodules can be assessed with reassuring accuracy using ultrasound and the guidelines developed by the American Thyroid Association.

Ultrasound assessment is the first step of the evaluation of any patient with one or more thyroid nodules. “Maybe it shouldn’t be, but, for now, it is,” noted David L. Steward, MD, at the annual meeting of the American Thyroid Association.

The ATA guidelines categorize thyroid nodules on the basis of their ultrasound patterns, with the high risk of malignancy being in nodules that are taller than they are wide and /or have microcalcifications, irregular margins, hypoechoic areas, extrathyroidal extension, interrupted rim calcification with soft tissue extrusion, and suspicious lymph nodes. Between 70% and 90% of thyroids with such patterns will contain malignancy, according to the ATA guidelines. Lesions with an intermediate risk of malignancy have such sonographic findings as hypoechoic solid tissue and regular margins; between 10% and 20% of these are malignant. The third category in the ATA’s guidelines are those that are of low suspicion, with hyperechoic solid tissue, isoechoic solid tissue, partially cystic with eccentric solid area, and regular margins; 5%-10% of these are malignant. Thyroid nodules with a very-low risk of malignancy (less than 3%) are spongiform or partially cystic with no suspicious findings. Finally, benign nodules, of which less than 1% contain malignancy, are cysts, he said.

“We found that the size of the nodule on ultrasound that underwent fine needle aspiration was inversely correlated with malignancy risk: The lower risk nodules were larger,” he said.

Using the ATA’s system, 9 (4%) of the nodules were high risk, 64 (31%) were intermediate risk, 79 (38%) were low risk, 54 (26%) were very-low risk, and none were benign. Five of the nodules were not included in the results presented.

There was good correlation between the Bethesda and ATA classification systems. Of the lesions that were malignant or suspicious for malignancy in the Bethesda system, 77% were very-high risk for malignancy on ultrasound according to the ATA. Of the lesions that were atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), 22% were very high risk according to the ATA. Neither of the systems classified as malignant any of the lesions as follicular/Hurthle cell cancer, benign, or nondiagnostic.

The AUS/FLUS nodules “tend to be all over the map,” he noted. Looking at just the AUS/FLUS nodules, malignancy was found on pathology in 100% classified by the ATA system as being high risk; in 21% of those called intermediate risk; in 17% of those called low risk; and in 12% of the very-low risk group.

The study was funded by the University of Cincinnati. Dr. Steward said his only disclosure is that he was a member of the ATA committee that wrote the guidelines under evaluation in this study.

[email protected]

BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.

Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.

EPIC findings

For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.

Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.

For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)

Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).

The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.

BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.

Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.

EPIC findings

For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.

Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.

For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)

Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).

The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.

BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.

Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.

EPIC findings

For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.

Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.

For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)

Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).

The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.

BOSTON – Robot-assisted radical hysterectomy is just as safe, or perhaps safer, than open surgery, according to a new study that examined perioperative and postoperative outcomes with long-term follow-ups for both types of procedures.

“Robotic surgery has been expanding for the last 20 years, but still the recurrence rate with cancer patients is missing data because very few studies are published; they don’t have long-term oncologic outcomes, and if [the technology] works properly we have to put it into the literature,” M. Bilal Sert, MD, of Oslo University, said at the annual Minimally Invasive Surgery Week.

Dr. Sert and his coinvestigators identified 215 women who underwent either open or robot-assisted radical hysterectomy between November 2005 and December 2012. All of the procedures were elective and the robot-assisted operations were performed using the da Vinci robotic surgical platform. After excluding neoadjuvant cases, which totaled 19, the researchers looked at data on 196 patients (122 open radical hysterectomy cases and 74 robot-assisted radical hysterectomy cases).

On average, operating time for open radical hysterectomy was 171 minutes, versus 263 minutes for robot-assisted radical hysterectomy. However, the robotic surgery arm had lower mean estimated blood loss than the open surgery cohort: 80 milliliters versus 468 milliliters, respectively (P = .003). Follow-up time frames were shorter in the robotic surgery cohort by 6 months: 46 months reported for robotic surgery, compared with a 52-month average experienced by those in the open surgery cohort.

Both groups experienced recurrences, including 12 patients in the open surgery cohort (9.8%) and 9 patients in the robotic surgery cohort (12.1%) (P = .3), indicating a statistically insignificant difference. Similarly, rates of perioperative complications were 8% for open surgery and 11% for robotic surgery (P = .3), which was not significantly different.

However, rates of postoperative complications were 36% for open surgery and 12% for robotic surgery (P = .001), which was statistically significant.

“Based on our data, I can say that [robot-assisted radical hysterectomy] is safe, and in fact I prefer to use the robot,” Dr. Sert said at the meeting, which was held by the Society of Laparoendoscopic Surgeons. “Of course, robot-assisted surgery will not automatically make you a better surgeon, but on more complicated radical hysterectomy patients, it will help make the surgeon more precise.”

No funding source was disclosed for this study. Dr. Sert reported having no relevant financial disclosures.

[email protected]

BOSTON – Robot-assisted radical hysterectomy is just as safe, or perhaps safer, than open surgery, according to a new study that examined perioperative and postoperative outcomes with long-term follow-ups for both types of procedures.

“Robotic surgery has been expanding for the last 20 years, but still the recurrence rate with cancer patients is missing data because very few studies are published; they don’t have long-term oncologic outcomes, and if [the technology] works properly we have to put it into the literature,” M. Bilal Sert, MD, of Oslo University, said at the annual Minimally Invasive Surgery Week.

Dr. Sert and his coinvestigators identified 215 women who underwent either open or robot-assisted radical hysterectomy between November 2005 and December 2012. All of the procedures were elective and the robot-assisted operations were performed using the da Vinci robotic surgical platform. After excluding neoadjuvant cases, which totaled 19, the researchers looked at data on 196 patients (122 open radical hysterectomy cases and 74 robot-assisted radical hysterectomy cases).

On average, operating time for open radical hysterectomy was 171 minutes, versus 263 minutes for robot-assisted radical hysterectomy. However, the robotic surgery arm had lower mean estimated blood loss than the open surgery cohort: 80 milliliters versus 468 milliliters, respectively (P = .003). Follow-up time frames were shorter in the robotic surgery cohort by 6 months: 46 months reported for robotic surgery, compared with a 52-month average experienced by those in the open surgery cohort.

Both groups experienced recurrences, including 12 patients in the open surgery cohort (9.8%) and 9 patients in the robotic surgery cohort (12.1%) (P = .3), indicating a statistically insignificant difference. Similarly, rates of perioperative complications were 8% for open surgery and 11% for robotic surgery (P = .3), which was not significantly different.

However, rates of postoperative complications were 36% for open surgery and 12% for robotic surgery (P = .001), which was statistically significant.

“Based on our data, I can say that [robot-assisted radical hysterectomy] is safe, and in fact I prefer to use the robot,” Dr. Sert said at the meeting, which was held by the Society of Laparoendoscopic Surgeons. “Of course, robot-assisted surgery will not automatically make you a better surgeon, but on more complicated radical hysterectomy patients, it will help make the surgeon more precise.”

No funding source was disclosed for this study. Dr. Sert reported having no relevant financial disclosures.

[email protected]

BOSTON – Robot-assisted radical hysterectomy is just as safe, or perhaps safer, than open surgery, according to a new study that examined perioperative and postoperative outcomes with long-term follow-ups for both types of procedures.

“Robotic surgery has been expanding for the last 20 years, but still the recurrence rate with cancer patients is missing data because very few studies are published; they don’t have long-term oncologic outcomes, and if [the technology] works properly we have to put it into the literature,” M. Bilal Sert, MD, of Oslo University, said at the annual Minimally Invasive Surgery Week.

Dr. Sert and his coinvestigators identified 215 women who underwent either open or robot-assisted radical hysterectomy between November 2005 and December 2012. All of the procedures were elective and the robot-assisted operations were performed using the da Vinci robotic surgical platform. After excluding neoadjuvant cases, which totaled 19, the researchers looked at data on 196 patients (122 open radical hysterectomy cases and 74 robot-assisted radical hysterectomy cases).

On average, operating time for open radical hysterectomy was 171 minutes, versus 263 minutes for robot-assisted radical hysterectomy. However, the robotic surgery arm had lower mean estimated blood loss than the open surgery cohort: 80 milliliters versus 468 milliliters, respectively (P = .003). Follow-up time frames were shorter in the robotic surgery cohort by 6 months: 46 months reported for robotic surgery, compared with a 52-month average experienced by those in the open surgery cohort.

Both groups experienced recurrences, including 12 patients in the open surgery cohort (9.8%) and 9 patients in the robotic surgery cohort (12.1%) (P = .3), indicating a statistically insignificant difference. Similarly, rates of perioperative complications were 8% for open surgery and 11% for robotic surgery (P = .3), which was not significantly different.

However, rates of postoperative complications were 36% for open surgery and 12% for robotic surgery (P = .001), which was statistically significant.

“Based on our data, I can say that [robot-assisted radical hysterectomy] is safe, and in fact I prefer to use the robot,” Dr. Sert said at the meeting, which was held by the Society of Laparoendoscopic Surgeons. “Of course, robot-assisted surgery will not automatically make you a better surgeon, but on more complicated radical hysterectomy patients, it will help make the surgeon more precise.”

No funding source was disclosed for this study. Dr. Sert reported having no relevant financial disclosures.

[email protected]

Just as Charlie Brown looks forward to the coming of the Great Pumpkin each Halloween, those of us who dance in the minefields of payment policy await the publication of the Proposed Rule, more formally known as the “Revisions to Payment Policies under the Physician Fee Schedule and Other Revisions to Part B for CY 2017.”^1,2 You could read the entire tome—a mere 316 pages (excluding the hundreds of pages of granular supplement data discussed in the last few columns)—or simply read what I have outlined as the good, the bad, and the ugly for the Proposed Rule for 2017.

The Good

In 2017, dermatology will increase its share of the pie by 1% to $3.505 billion of a total $89.467 billion expected to be expended for physician services.¹ The effect on individual providers will vary by geographic location and practice mix. Half is from the 0.5% increase that has come to all physicians across the board as mandated by the Medicare Access and CHIP Reauthorization Act (MACRA).³

Current Procedural Terminology (CPT) codes for reflectance confocal microscopy (96931–96936) will have Centers for Medicare & Medicaid Services valuations beginning in 2017, and individuals performing this service should be able to report it and be paid for their efforts.¹ The values are below the American Medical Association/Specialty Society Relative Value Scale Update Committee (RUC) recommendations.

The Bad

Payment rates for 2017 will be based on a conversion factor of 35.7751,¹ a drop from the 2016 conversion factor of 35.8043. Cuts will be made for some specialties. Gastroenterology, nephrology, neurosurgery, radiology, urology, and radiation therapy centers will take a 1% hit; ophthalmology, pathology, and vascular surgery will take 2% cuts; and interventional radiology will lose 7%.¹ A special case within dermatology and pathology is a 15% cut to the technical component of slide preparation for CPT code 88305⁴ due to a redefinition of the valuation of eosin stains.² While the accuracy and precision of the value of these practice expense inputs can be debated, the government by definition makes the rules and involved specialties had an opportunity to appeal this change through the comment process that ended on September 6, 2016. The government can take comments into account, but substantial changes usually are not made from the Proposed Rule to the Final Rule, which usually arrives around the beginning of November; however, in an election year, the Final Rule can be a few weeks late.

The Ugly

The government will increase its unfunded mandates with the creation of new Medicare G codes (global services codes) that will allow the government to track the provision of postoperative care for all 010 and 090 global service periods (Table 1). The codes look mostly at time and do not clearly take into account the severity or complexity of the conditions being cared for and will be reported on claim forms as an unfunded mandate with more confusion and cost.¹ Because not all claim-paying intermediaries are likely to have these G codes smoothly set up in their systems, there will still be a cost to filing the claim. Unless changes occur in the Final Rule, which is unlikely, there will be no payment for the time and effort of submitting these claims. The goal of the US Government is to hone in on postoperative services and parse them down so they can cut payments wherever possible beginning in 2019.¹ Everyone wants to save money, from the consumer⁵ to the payer, and the ultimate payer is playing hardball. Additional validation efforts likely will lower physician fee-for-service payments further.

The US Government also is taking a shot at what they call “misvalued services” that have not had recent refinement within the RUC process.¹ The work list for 2017 includes a number of 000 global period codes where additional evaluation and management services are reported using modifier -25, which implies a substantial, separately identifiable cognitive service performed by the same physician on the day of a procedure above and beyond other services provided or beyond the usual preservice and postservice care associated with the procedure that was performed. Although codes such as biopsies (11100 and 11101) and premalignant destructions (17000–17004) have an adjustment built in and dermatologists who provide services on the same day are actually penalized for the multiple built-in reductions that are already additive, the government is concerned that 19% of the 000 global services were billed more than 50% of the time with an evaluation and management code with modifier -25. Eighty-three codes met the criteria for which the government believes it may be overpaying¹; the codes of interest to dermatology are shown in Table 2.¹

Final Thoughts

I end this column with an appeal to the dermatologists of America. Go to the American Academy of Dermatology Association Political Action Committee website (https://skinpac.org/), the home page for the only political action committee that represents the dermatology specialty, and consider making a donation. Emergency medicine physicians created the “Giving a Shift” campaign, which is a donation to their national political action committee of one shift’s earnings, and most of us could easily donate a half day’s income, as the only way to potentially change the increasingly onerous burdens on practitioners is through political action. As we say at RUC meetings, you can eat lunch or be lunch. The choice is yours.

Just as Charlie Brown looks forward to the coming of the Great Pumpkin each Halloween, those of us who dance in the minefields of payment policy await the publication of the Proposed Rule, more formally known as the “Revisions to Payment Policies under the Physician Fee Schedule and Other Revisions to Part B for CY 2017.”^1,2 You could read the entire tome—a mere 316 pages (excluding the hundreds of pages of granular supplement data discussed in the last few columns)—or simply read what I have outlined as the good, the bad, and the ugly for the Proposed Rule for 2017.

The Good

In 2017, dermatology will increase its share of the pie by 1% to $3.505 billion of a total $89.467 billion expected to be expended for physician services.¹ The effect on individual providers will vary by geographic location and practice mix. Half is from the 0.5% increase that has come to all physicians across the board as mandated by the Medicare Access and CHIP Reauthorization Act (MACRA).³

Current Procedural Terminology (CPT) codes for reflectance confocal microscopy (96931–96936) will have Centers for Medicare & Medicaid Services valuations beginning in 2017, and individuals performing this service should be able to report it and be paid for their efforts.¹ The values are below the American Medical Association/Specialty Society Relative Value Scale Update Committee (RUC) recommendations.

The Bad

Payment rates for 2017 will be based on a conversion factor of 35.7751,¹ a drop from the 2016 conversion factor of 35.8043. Cuts will be made for some specialties. Gastroenterology, nephrology, neurosurgery, radiology, urology, and radiation therapy centers will take a 1% hit; ophthalmology, pathology, and vascular surgery will take 2% cuts; and interventional radiology will lose 7%.¹ A special case within dermatology and pathology is a 15% cut to the technical component of slide preparation for CPT code 88305⁴ due to a redefinition of the valuation of eosin stains.² While the accuracy and precision of the value of these practice expense inputs can be debated, the government by definition makes the rules and involved specialties had an opportunity to appeal this change through the comment process that ended on September 6, 2016. The government can take comments into account, but substantial changes usually are not made from the Proposed Rule to the Final Rule, which usually arrives around the beginning of November; however, in an election year, the Final Rule can be a few weeks late.

The Ugly

The government will increase its unfunded mandates with the creation of new Medicare G codes (global services codes) that will allow the government to track the provision of postoperative care for all 010 and 090 global service periods (Table 1). The codes look mostly at time and do not clearly take into account the severity or complexity of the conditions being cared for and will be reported on claim forms as an unfunded mandate with more confusion and cost.¹ Because not all claim-paying intermediaries are likely to have these G codes smoothly set up in their systems, there will still be a cost to filing the claim. Unless changes occur in the Final Rule, which is unlikely, there will be no payment for the time and effort of submitting these claims. The goal of the US Government is to hone in on postoperative services and parse them down so they can cut payments wherever possible beginning in 2019.¹ Everyone wants to save money, from the consumer⁵ to the payer, and the ultimate payer is playing hardball. Additional validation efforts likely will lower physician fee-for-service payments further.

The US Government also is taking a shot at what they call “misvalued services” that have not had recent refinement within the RUC process.¹ The work list for 2017 includes a number of 000 global period codes where additional evaluation and management services are reported using modifier -25, which implies a substantial, separately identifiable cognitive service performed by the same physician on the day of a procedure above and beyond other services provided or beyond the usual preservice and postservice care associated with the procedure that was performed. Although codes such as biopsies (11100 and 11101) and premalignant destructions (17000–17004) have an adjustment built in and dermatologists who provide services on the same day are actually penalized for the multiple built-in reductions that are already additive, the government is concerned that 19% of the 000 global services were billed more than 50% of the time with an evaluation and management code with modifier -25. Eighty-three codes met the criteria for which the government believes it may be overpaying¹; the codes of interest to dermatology are shown in Table 2.¹

Final Thoughts

I end this column with an appeal to the dermatologists of America. Go to the American Academy of Dermatology Association Political Action Committee website (https://skinpac.org/), the home page for the only political action committee that represents the dermatology specialty, and consider making a donation. Emergency medicine physicians created the “Giving a Shift” campaign, which is a donation to their national political action committee of one shift’s earnings, and most of us could easily donate a half day’s income, as the only way to potentially change the increasingly onerous burdens on practitioners is through political action. As we say at RUC meetings, you can eat lunch or be lunch. The choice is yours.

Just as Charlie Brown looks forward to the coming of the Great Pumpkin each Halloween, those of us who dance in the minefields of payment policy await the publication of the Proposed Rule, more formally known as the “Revisions to Payment Policies under the Physician Fee Schedule and Other Revisions to Part B for CY 2017.”^1,2 You could read the entire tome—a mere 316 pages (excluding the hundreds of pages of granular supplement data discussed in the last few columns)—or simply read what I have outlined as the good, the bad, and the ugly for the Proposed Rule for 2017.

The Good

In 2017, dermatology will increase its share of the pie by 1% to $3.505 billion of a total $89.467 billion expected to be expended for physician services.¹ The effect on individual providers will vary by geographic location and practice mix. Half is from the 0.5% increase that has come to all physicians across the board as mandated by the Medicare Access and CHIP Reauthorization Act (MACRA).³

Current Procedural Terminology (CPT) codes for reflectance confocal microscopy (96931–96936) will have Centers for Medicare & Medicaid Services valuations beginning in 2017, and individuals performing this service should be able to report it and be paid for their efforts.¹ The values are below the American Medical Association/Specialty Society Relative Value Scale Update Committee (RUC) recommendations.

The Bad

Payment rates for 2017 will be based on a conversion factor of 35.7751,¹ a drop from the 2016 conversion factor of 35.8043. Cuts will be made for some specialties. Gastroenterology, nephrology, neurosurgery, radiology, urology, and radiation therapy centers will take a 1% hit; ophthalmology, pathology, and vascular surgery will take 2% cuts; and interventional radiology will lose 7%.¹ A special case within dermatology and pathology is a 15% cut to the technical component of slide preparation for CPT code 88305⁴ due to a redefinition of the valuation of eosin stains.² While the accuracy and precision of the value of these practice expense inputs can be debated, the government by definition makes the rules and involved specialties had an opportunity to appeal this change through the comment process that ended on September 6, 2016. The government can take comments into account, but substantial changes usually are not made from the Proposed Rule to the Final Rule, which usually arrives around the beginning of November; however, in an election year, the Final Rule can be a few weeks late.

The Ugly

The government will increase its unfunded mandates with the creation of new Medicare G codes (global services codes) that will allow the government to track the provision of postoperative care for all 010 and 090 global service periods (Table 1). The codes look mostly at time and do not clearly take into account the severity or complexity of the conditions being cared for and will be reported on claim forms as an unfunded mandate with more confusion and cost.¹ Because not all claim-paying intermediaries are likely to have these G codes smoothly set up in their systems, there will still be a cost to filing the claim. Unless changes occur in the Final Rule, which is unlikely, there will be no payment for the time and effort of submitting these claims. The goal of the US Government is to hone in on postoperative services and parse them down so they can cut payments wherever possible beginning in 2019.¹ Everyone wants to save money, from the consumer⁵ to the payer, and the ultimate payer is playing hardball. Additional validation efforts likely will lower physician fee-for-service payments further.

The US Government also is taking a shot at what they call “misvalued services” that have not had recent refinement within the RUC process.¹ The work list for 2017 includes a number of 000 global period codes where additional evaluation and management services are reported using modifier -25, which implies a substantial, separately identifiable cognitive service performed by the same physician on the day of a procedure above and beyond other services provided or beyond the usual preservice and postservice care associated with the procedure that was performed. Although codes such as biopsies (11100 and 11101) and premalignant destructions (17000–17004) have an adjustment built in and dermatologists who provide services on the same day are actually penalized for the multiple built-in reductions that are already additive, the government is concerned that 19% of the 000 global services were billed more than 50% of the time with an evaluation and management code with modifier -25. Eighty-three codes met the criteria for which the government believes it may be overpaying¹; the codes of interest to dermatology are shown in Table 2.¹

Final Thoughts

I end this column with an appeal to the dermatologists of America. Go to the American Academy of Dermatology Association Political Action Committee website (https://skinpac.org/), the home page for the only political action committee that represents the dermatology specialty, and consider making a donation. Emergency medicine physicians created the “Giving a Shift” campaign, which is a donation to their national political action committee of one shift’s earnings, and most of us could easily donate a half day’s income, as the only way to potentially change the increasingly onerous burdens on practitioners is through political action. As we say at RUC meetings, you can eat lunch or be lunch. The choice is yours.