Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

Fresh produce

New research suggests that cancer survivors in the US may need dietary interventions to improve their health.

The study showed that, overall, cancer survivors did not adhere to federal dietary guidelines as well as a matched control population.

Cancer survivors tended to consume more empty calories and less fiber than controls.

Fang Fang Zhang, MD, PhD, of Tufts University in Boston, Massachusetts, and his colleagues reported these findings in Cancer.

The team evaluated the diets of 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010. The investigators also assessed the diets of 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity.

The goal was to determine how subjects’ diets aligned with advice from the 2010 Dietary Guidelines for Americans, which was jointly issued by the Department of Agriculture and the Department of Health and Human Services.

Cancer survivors had poor adherence to the guidelines, with a total Healthy Eating Index score of 47.2 out of 100, compared with a score of 48.3 in the adults without a history of cancer (P=0.03).

Cancer survivors had a significantly lower mean score for empty calories compared to the noncancer group—13.6 and 14.4, respectively (P=0.001). This suggested the cancer group had a higher consumption of calories from solid fats, alcohol, and added sugars.

Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group—15.0 and 15.9 g per day, respectively (P=0.02).

Compared to recommended values, cancer survivors had low dietary intakes of vitamin D (31% of the recommended intake), vitamin E (47%), potassium (55%), and calcium (73%) but high intakes of saturated fat (112%) and sodium (133%).

The investigators noted that diet quality in cancer survivors increased linearly with age. The older the age, the better the diet quality.

Survivors with lower education (high school or less) had significantly worse diet quality than those with higher education. And survivors who were current smokers had significantly worse diet quality than non-smokers or former smokers.

For the 4 major cancer types in the US (breast, prostate, lung, and colorectal), breast cancer survivors had the best diet quality, and lung cancer survivors had the worst diet quality.

The investigators said that knowing how well cancer survivors adhere to federal dietary guidelines can help inform evidence-based priorities for improving their nutritional intake.

“Dietary changes that include more fiber, fruit, and vegetables in the diet and less fat, sodium, and added sugar would be important for cancer survivors,” Dr Zhang said.

“Oncology care providers can play critical roles in reinforcing the importance of a healthful diet and can refer patients to registered dietitians who are experts in oncology care or to other reputable sources in order to improve survivors’ overall health.”

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

It was not long ago that acne vulgaris (AV) was commonly considered to be a skin disease that affected teenagers with little attention given to preadolescent and postadolescent AV. This perspective has changed, with more attention being given to AV across a broad range of affected 
age groups, including preadolescent, adolescent, and postadolescent subgroups.^1-5 Earlier onset of adrenarche has led to earlier development of AV in many young girls, with a higher range of dehydroepiandrosterone sulfate (DHEAS) levels observed overall in those with AV as compared to a normal age-matched population.^3,4 At the other end of the age spectrum, AV is a common phenomenon in adult females, with at least half of women estimated to exhibit some form of AV.^1,2,5-8 Based on a 
large survey of females and males (N=1013), the prevalence of AV in adult females has been reported to be 50.9%, 35.2%, 26.3%, and 15.3% among women aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older, respectively.² Acne vulgaris that persists beyond adolescence into adulthood is termed persistent acne, or early-onset acne, and the development of AV in women 25 years and older who have not previously been affected by AV has been termed late-onset acne.^6,8,9 Publications on the management of AV in adult women have focused primarily on systemic hormonal therapies; however, topical therapies more recently have received greater attention in this subpopulation^9-12 and will be discussed in part 2 of this series. Because data on AV in women are 
limited primarily to involvement of the face and neck region, this article does not address truncal AV unless otherwise specified. Table 1 depicts factors that can influence the management of AV in adult women.

Visible Patterns and Considerations for Clinical Evaluation 


Clinical Patterns

Although epidemiologic and demographic data are limited in the subpopulation of women with AV, it is reported that females account for up to 82% of adults with AV, with approximately 75% presenting with AV that is clinically similar to their disease course in adolescence.^2,5,13 Among those women with persistent AV, some state that their AV is worse compared to adolescence, while others report it is not as severe. The pattern of AV often is similar to that seen in adolescence, presenting as mixed comedonal and inflammatory papular/pustular lesions diffusely distributed on the face; in other cases, a more selectively distributed U-shaped pattern is noted, characterized predominantly by inflammatory papules and/or nodules involving the lower cheeks and jawline margin, with lesions also commonly noted on the anterior and lateral neck.^5,8,9,13-16 A U-shaped pattern is believed to be more common in late-onset AV, often with persistence into the mid-40s.^1,15,17 It is important to emphasize the need for additional studies on the demographics and clinical characteristics of AV in adult females, especially correlations between onset, age, and clinical patterns of AV.

An international, prospective, observational study assessed the clinical characteristics of AV in adults (aged ≥25 years) at a dermatology visit for acne (N=374).¹⁶ Participants who were under management for their AV showed severity grades of mild (clear/almost clear) in 47.3% of cases. Involvement of multiple facial sites—cheeks, forehead, mandibular region, and temples—was noted in 89.8% of women, often with both inflammatory and comedonal lesions, which is a pattern similar to adolescent AV. Inflammatory lesions alone were observed in 6.4% of women, 17.1% had comedonal AV only, 
and truncal AV was present in 48.4%.¹⁶ Additional well-designed studies are needed to determine if this study reflects an accurate qualitative and 
quantitative depiction of the spectrum of AV in adult females.

Mandibular Pattern

In the observational study of AV in adults, AV localized to the mandibular area was noted in only 11.2% of participants.¹⁶ Women with localized mandibular AV were more likely than women without localized AV to be employed, noted greater daily stress levels, and tended to report more psychologically stressful jobs. Interestingly, the subgroup with mandibular acne alone was much less likely 
to exhibit a global severity grade of moderate or higher (7.1% vs 50.1%), truncal acne 
(19.0% vs 51.9%), postinflammatory hyperpigmentation (23.8% vs 51.9%), and erythema (19.0% vs 48.4%), suggesting a unique subset of AV presentation.¹⁶

Ethnicity/Skin Color

Women of all ethnicities and skin types may be affected by AV.^1,18-20 Earlier age of onset of AV has been suggested in white women; however, earlier onset of adrenarche may be more frequent in black girls, which supports an earlier age of onset of AV in this subpopulation.^15-17 Women with skin of color usually express greater concern with persistent dyschromia at sites where lesions have resolved, and presence of acne scars is a concern among women regardless of skin color, ethnicity, or race.^18,20-22

Scarring

Acne scarring has been noted to affect up to 
three-fourths of adult women in one report¹⁷ and 
often is stated by patients to be a cause of concern 
and frustration.^1,5,17

Perimenstrual Flaring

Flaring associated with menses is commonly reported in adult females with AV, with 56%, 17%, and 
3% of women in one study (n=230) reporting worsening before, during, or after menses, respectively.²¹

External Factors

Comedogenic products used for skin care, cover-up makeup, or hair care may be important to consider in selected cases as potential etiologic or exacerbating factors in adult females with AV; they also may be used in the management of AV.^23-25 Adult females often are perplexed and frustrated by the presence of AV after their 
teenaged years and anxiously wonder about or search for the potential causes. Many women use cosmetic products to cover up facial AV.^5,23-25 Therefore, even if skin care or personal hygiene products or makeup are not believed to be an etiologic factor, many patients appreciate that their dermatologist addressed skin care and cosmetics as a component of AV management and provided appropriate recommendations.^5,13

Ingestion of dietary supplements containing whey protein have been associated with precipitation of AV.^26,27 Diets with specific content characteristics have been implicated as potential etiologic or exacerbating factors for AV; however, data are limited and specific recommendations remain elusive at present. Individual cases may warrant consideration of dietary factors, especially when treatment resistance is noted.²⁸ Importantly, progestin-only contraceptives (ie, injectables, intrauterine devices) also can exacerbate or induce AV.²⁹

Hyperandrogenism

Although most adult females with AV are reported to have normal serum androgen levels when tested, it is important to explore potential signs and symptoms that are suggestive of underlying hyperandrogenism through both the patient’s history and physical examination.^{9-11,21,29-33} Some investigators have suggested that underlying peripheral hyperandrogenism is the leading cause of AV in adult females, 
with or without concurrent polycystic ovarian syndrome (PCOS), though it is believed that most women with AV exhibit normal results when 
undergoing laboratory testing for androgen excess.^{10,11,21,29,30} Nevertheless, it is important to consider the possibility of underlying causes of androgen excess (Table 2), the most common being PCOS and late-onset congenital adrenal hyperplasia; an androgen-secreting tumor is less common.^11,29-33 It is suggested that screening for underlying endocrinopathy should be conducted in women presenting with (1) AV recalcitrant to conventional treatment, (2) sudden emergence of severe AV, 
(3) concurrent signs/symptoms of androgen 
excess, and/or (4) AV relapse shortly after isotretinoin therapy.^7,11,16,33

Hirsutism and acanthosis nigricans have been reported to be more reliable predictors of hyperandrogenism than androgenic alopecia.²¹ Although it may be subtle in some cases, acanthosis nigricans is harder to camouflage, so the clinician can usually detect it if a thorough physical examination is performed. However, a patient may not voluntarily report to the clinician and their staff that she has hair removed, so despite a thorough examination, the clinician may not detect hirsutism. Therefore, it is important to inquire directly about the presence of hairs (pigmented terminal vs “peach fuzz” hairs), their anatomic location, and any hair removal practices the patient has used. The absence of androgenic alopecia does not exclude underlying hyperandrogenism; however, its presence, especially in younger women, may serve as a clinical marker for underlying hyperandrogenism.⁵ Some women may camouflage more subtle alopecia through hairstyling, but obtaining this history usually is not problematic, as most women are distressed by any degree of hair loss.

Laboratory Evaluation—A relatively straightforward approach to the workup of androgen excess includes assessment of serum DHEAS, free testosterone, and total testosterone levels.^10,30 Elevation of serum DHEAS levels indicates an adrenal source of androgen production. Elevation of testosterone is associated with excess androgens 
produced by the ovaries. Modest elevations of 
DHEAS are most commonly associated with late-onset congenital adrenal hyperplasia that may not have been previously diagnosed. Modest elevation 
of testosterone is most commonly associated with PCOS, which also can be accompanied by an 
elevated luteinizing hormone:follicle-stimulating hormone ratio of 2.5:1 to 3:1.^10,30 Marked elevations of DHEAS or testosterone can be indicative of adrenal or ovarian tumors, respectively.³⁰

In some cases, a woman might have 
elevated DHEAS and testosterone levels. A 17-hydroxyprogesterone test can help discriminate between an adrenal or ovarian source of 
androgen excess in these cases, as elevated 
17-hydroxyprogesterone levels indicate that the androgens are coming from the adrenal gland.^10,30

It is important that laboratory evaluation be performed when ovulation is not occurring. Blood tests can be drawn just prior to or during menses. It is important that a woman is not taking an oral contraceptive at the time of testing, which can mask an underlying endocrine abnormality.^10,11,29,30 Generally, testing can be performed at least 4 to 6 weeks after stopping the oral contraceptive.

Psychosocial Impact

Facial AV exhibits a broad range of adverse psychological and social effects on many adult females.^2,5,13,18 It can be associated with depression, anxiety, psychological stress, and suicidal ideation; therefore, thorough screening for these comorbidities may be warranted in some patients.^2,18

Conclusion

The epidemiology, clinical presentation, and clinical and laboratory evaluation of AV in adult females was reviewed in part 1 of this 3-part series. It is important for the clinician to assess the clinical presentation, psychosocial effects, and the possibility of underlying causes of androgen excess. In part 2, skin care 
and topical management of AV in adult females will be discussed.

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Blood for transfusion

Photo by Juan D. Alfonso

CHICAGO—Researchers say an electronic tracking system has enabled a group of hospitals to significantly reduce the amount of blood transfused after operations.

This system also cut costs by an estimated $2.5 million over 2 years and contributed to lower infection rates without harming patients.

These results were presented at the 2015 Clinical Congress of the American College of Surgeons and published in the Journal of the American College of Surgeons.

In 2012, Intermountain Healthcare implemented the blood ordering and tracking system, along with a program to educate hospital staff, in 22 hospitals across Utah. This includes trauma centers, small rural hospitals, and large community medical centers.

Intermountain employs approximately 1200 physicians and 550 advanced practice clinicians, and another 3000 to 4000 independent physicians have privileges at Intermountain hospitals.

Before Intermountain implemented its blood tracking system, general surgeons, orthopedic surgeons, and urologists each used different hematocrit levels to order blood.

Now, Intermountain uses a consistent threshold across all disciplines—less than 23%. However, physicians can still order blood for patients with hematocrit above that threshold when they feel it is medically necessary.

Results

In 2011, 6% of all patients at Intermountain facilities received blood. Today, only 4% do, according to study author Mark J. Ott, MD, chief medical director of Intermountain Healthcare’s central region.

“So a third of our patients didn’t get blood who used to,” Dr Ott said. “That’s a giant change. That’s tens of thousands of units of blood a year that didn’t get used.”

Before the program started (January 1, 2012), Intermountain facilities transfused almost 50 units of packed red blood cells per 1000 patient days. By January 31, 2015, that rate had declined to about 35.5 units, a reduction of around 30%.

Over the same time period, the percentage of patients transfused with a hematocrit of 23% or greater decreased from 60% to 34%.

The researchers said these reductions in blood use reduced costs by about $2.5 million over the 2-year period, assuming each unit of packed red blood cells costs $300.

In addition, the rate of hospital-acquired infections for both the general hospital population and patients who received blood declined significantly over the 2-year period.

The overall infection rate fell from 1.66 to 0.81 per 1000 patient days. Among patients who received blood, infection rates declined around 33%.

Dr Ott noted that the reduction in infections was also impacted by other initiatives within the health system aimed at reducing surgical site infections and ambulating patients earlier after operations.

“So I cannot tell you that those decreases in hospital-acquired infections are solely due to patients receiving less blood, but it’s part of the picture,” he said. “And we did not see worse outcomes in patients.”

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.

Doctor examines patient

Photo by Logan Tuttle

Results of 2 studies suggest eltrombopag can be safe and effective in children of all ages affected by chronic immune thrombocytopenia (ITP).

In both trials, patients who received eltrombopag were significantly more likely to achieve stable platelet counts than patients who received placebo.

And eltrombopag did not increase the rate of serious adverse events (AEs).

These studies are the phase 2 PETIT trial, which was published in The Lancet Haematology, and the phase 3 PETIT2 trial, which was published in The Lancet.

“The studies, funded by GlaxoSmithKline, provide clinicians with much-needed evidence to help decide when eltrombopag would benefit pediatric patients and provide dosage regimens suitable for pediatric patients,” said investigator John Grainger, PhD, of The University of Manchester in the UK.

Phase 2 trial

The PETIT trial included 67 ITP patients who were stratified by age cohort (12-17 years, 6-11 years, and 1-5 years) and randomized (2:1) to receive eltrombopag or placebo for 7 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects achieving platelet counts of 50 x 10⁹/L or higher at least once between days 8 and 43 of the randomized period of the study.

Significantly more patients in the eltrombopag arm met this endpoint—62.2%—compared to 31.8% in the placebo arm (P=0.011).

The most common AEs (in the eltrombopag and placebo groups, respectively) were headache (30% vs 43%), upper respiratory tract infection (25% vs 10%), and diarrhea (16% vs 5%).

Grade 3/4 AEs occurred in 11% of patients receiving eltrombopag and 19% of patients receiving placebo. Serious AEs occurred in 9% and 10%, respectively. There were no thrombotic events or malignancies in either group.

Phase 3 trial

The PETIT2 trial included 92 patients with chronic ITP who were randomized (2:1) to receive eltrombopag or placebo for 13 weeks. The eltrombopag dose was titrated to a target platelet count of 50-200 x 10⁹/L.

The primary efficacy endpoint was the proportion of subjects who achieved platelet counts of 50 x 10⁹/L or higher for at least 6 out of 8 weeks, between weeks 5 and 12 of the randomized period.

Significantly more patients in the eltrombopag arm met this endpoint—41.3%, compared to 3.4% of patients in the placebo arm (P<0.001).

AEs that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (17%), rhinitis (16%), upper respiratory tract infection (11%), and cough (11%).

Serious AEs occurred in 8% of patients who received eltrombopag and 14% who received placebo. There were no deaths, malignancies, or thromboses during this trial.

It was based on these studies that eltrombopag was approved for use in US children older than 1 year of age. The drug is currently under review for this indication in the European Union.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

I am a relatively young physician. When I started medical school 10 years ago, I thought that most medical school campuses would be fairly progressive. This was not the case for me.

My school did not have a nondiscrimination policy on sexual orientation or gender identity at the time, nor do I recall any lectures about this patient population. So during my first year of medical school, I embarked on a mission to educate both my classmates and the faculty about sexual orientation, gender identity, and related health disparities. My fellow classmates and the administration received my efforts warmly; nevertheless, this effort to educate was an incredible challenge for me. Surely other medical school campuses were already discussing the importance of sexuality and gender identity, I thought.

Fast forward to the year 2011. A study in JAMA found that many medical schools fall short in teaching the next generation of physicians about lesbian, gay, bisexual, and transgender (LGBT) health (JAMA. 2011;306[9]:971-7).

Things may have improved for LGBT people, but the world of medicine has yet to catch up. If LGBT medical education is lacking today, imagine how lacking it was for those who went to medical school decades ago. It is my hope that with this new column, we as a medical community can make up for lost time.

Why should physicians, especially pediatricians, care about LGBT health? Although LGBT youth comprise less than 10% of the adolescent population, they have a disproportionate share of health problems compared with their heterosexual peers. LGBT youth are three times as likely to attempt suicide and almost two times as likely to abuse alcohol and drugs compared with heterosexual youth. Among homeless teens in the United States, a whopping 40% are LGBT. HIV still plagues young gay males – especially those of color – and young gay and bisexual women experience an inordinate amount of dating violence from both men and women. Most appalling of all, every 3 days, a transgender person is murdered. These sobering statistics highlight the impact sexual orientation and gender identity have on health.

Why do LGBT youth experience such enormous health problems? A rich body of evidence points to stigma and discrimination as a likely cause. We are familiar with stories of how LGBT youth are kicked out of their homes after coming out to their parents or how male teens suffered bullying for being perceived as “too feminine.” Nonetheless, we tend to ignore the more subtle ways LGBT youth experience stigma and discrimination through our heterosexist language and behavior. Although we could dismiss the phrase “that’s so gay” as just another variation of “that’s so dumb,” an LGBT teen might think “if something is that dumb, then so am I.”

My fellow columnists and I hope that this column will help you get to know a very vulnerable, yet special, population. We will ask you to rethink what you have learned about sexuality and gender. Here, we will start with the basics.

What is the difference between sex and gender?

Sex is the biological distinction between male and female that is determined chromosomally (XX versus XY, although there are variations) and phenotypically, such as organs like the penis or vagina. Gender is a range of characteristics that a culture assigns as typically male and female, which encompasses both anatomy and behaviors. For example, an individual assigned as male because he was born with a penis is also expected to be proactive, a problem solver, stoic, and the breadwinner of the family. Although we’d like to believe that there are clear distinctions between the two solely on the basis of anatomy, we often see many people diverge from behaviors that are typically assigned to a gender. In modern day U.S. society, there are an increasing number of men who stay home to take care of their children – a typically female role. In other words, gender is a spectrum ranging from the very masculine to the very feminine and everything else in between.

What is gender identity?

Gender identity is our own sense of maleness or femaleness. This identity can be based on a variety of factors, including the sex organ one is born with and the culture one is raised in. It also is possible for some people to feel that they do not fit neatly into male or female categories. At the end of the day, only you can determine your gender identity, despite beliefs and attitudes in society about which appearances and behaviors are stereotypically male or female.

Transgender people are individuals who experience a mismatch between their gender identity and their assigned sex at birth. The word “trans” is Latin for “the other side,” highlighting the discrepancy between one’s gender identity and assigned sex. In contrast, people who identify as their assigned sex would be called cisgender. The word “cis” is Latin for “the same side.” A transgender male is someone who was assigned female at birth, but identifies as a male, whereas a transgender female is someone who was assigned male at birth, but identifies as a female. You also may also hear the terms “FTM” (female to male) and “MTF” (male to female) to describe transgender males and females, respectively.

What is sexual orientation?

Sexual orientation refers to our pattern of emotional and/or physical attraction to people who are the same or the opposite gender. The most common in this society is heterosexual, where one finds the opposite gender attractive. Those who identify as gay or lesbian find the same gender attractive. A person who identifies as bisexual finds both genders attractive. There are other sexual orientations that are not as commonly known. Someone who is pansexual is attracted to any sex or gender identity. Asexuals are individuals who don’t find anyone sexually attractive, but could be attracted to someone romantically or emotionally irrespective of sex or gender.

Just as gender is fluid, so is sexuality. Alfred Kinsey, a well-known sexologist, introduced the concept of sexual fluidity with the Kinsey Scale. With this scale, people rate themselves on how attracted they are to each sex, ranging from 0 – meaning exclusively attracted to the opposite sex – to 3 – equally attracted to both sexes – to 6 – exclusively attracted to the same sex. It is possible to move along the spectrum in either direction over time or stay in one place. It is also possible for our sexual identity (i.e. lesbian, gay, bisexual) and sexual behavior (i.e. whom we are having sex with) to not perfectly overlap; attraction is complex. Finally, people often confuse gender identity and sexual orientation. These are two separate concepts and not dependent on each other. For example, someone who was assigned female at birth but now identifies as male can still be attracted to men.

This primer is by no means complete or comprehensive and runs the risk of being oversimplistic. Nevertheless, I hope it will get you thinking about the nature of sexuality and gender identity and how they affect health. In the next couple of months, you will read more on the complexities of sexuality and gender identity, advice on how to talk to your patients about these topics, how to make your clinic a safe place for LGBT youth, the transition process for transgender youth, and much more. I encourage you stick around to learn how you can help this vulnerable, but amazing, group of young people. Until next time …

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of UPMC and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Michael Murphy, MD, the co-founder and CEO of ScribeAmerica, talks about the business model that has led to the growing use of medical scribes.

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

Listen to excerpts of Carol Patton’s interview, including Dr. Maki’s explaining the complexities of tandem surfing, his thoughts on the ocean’s spiritual appeal, and he and his wife’s work as intimacy therapists.

http://www.the-hospitalist.org/wp-content/uploads/2015/10/LanceMaki_FINAL-LO-Q_100715.mp3

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

For more videos from the Society of Gynecologic Surgeons, click here

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com

Contrary to popular belief, children with attention-deficit/hyperactivity disorder receiving psychostimulants have a decreased risk of anxiety, according to a meta-analysis by Catherine G. Coughlin and her associates.

Twenty-three studies involving 2,959 ADHD patients were included in the meta-analysis. Children who received methylphenidate derivatives were less likely to experience anxiety, with a relative risk of 0.85, while children receiving amphetamine derivatives had a risk similar to that of those on placebo. Medication acting over a short time also reduced anxiety risk (relative risk, 0.83), compared with long-acting psychostimulants and placebo.

©mik38/thinkstockphotos.com

A higher dosage was found to decrease the risk of anxiety, with the reduction similar for both amphetamine and MPH derivatives. Overall, the relative risk for all children with ADHD taking any psychostimulant was 0.86, compared with that of children receiving a placebo.

“Clinicians should further consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants but significant improvement in ADHD symptoms, as worsening anxiety symptoms are much more likely to be coincidental rather than caused by psychostimulants,” the investigators noted.

Find the study in the Journal of Child and Adolescent Psychopharmacology (doi: 10.1089/cap.2015.0075).

lfranki@frontlinemedcom.com