In Reply: I thank Drs. Kahlenborn and Severs for their comments. Controversy surrounds emergency contraception; thus, it is important to use peer-reviewed, current medical literature to reference mechanism of action. The product label is an unreliable resource, as it was written before current studies that clarified how emergency contraception works. The Noé study concluded that “levonorgestrel emergency contraception does not prevent embryo implantation and therefore cannot be labeled as abortifacient.”¹ They monitored ovulation via ultrasonography and hormonal assays, so they knew in which women ovulation had occurred when emergency contraception was taken. Of those who took it before ovulation, 16 pregnancies were expected and none occurred. When it was taken the day of ovulation or after, 8.7 pregnancies were expected and 8 pregnancies occurred. Because emergency contraception was ineffective after ovulation, a postfertilization effect is unlikely.

Although Drs. Kahlenborn and Severs cited 2004 Croxatto data, they did not cite the 2007 study by Novikova et al,² which concluded that levonorgestrel emergency contraception “has little or no effect on post-ovulation events, but is highly effective when taken before ovulation.”² In this study, when levonorgestrel emergency contraception was taken pre-ovulation, 0 out of 4 expected pregnancies occurred. When it was taken post-ovulation, 3 out of the 3 to 4 expected pregnancies occurred.²

The Frequently Asked Question 114 that Drs. Kahlenborn and Severs cited from the American Congress of Obstetricians and Gynecologists was updated in August 2011 and no longer cites prevention of implantation as a potential mechanism of action. Instead, it reads, “Progestin-only pills are thought to prevent pregnancy mainly by preventing ovulation.” ³ Another ACOG committee opinion, from November 2012, states, “A common misconception is that emergency contraception causes an abortion. Inhibition or delay of ovulation is the principal mechanism of action. Review of evidence suggests that emergency contraception cannot prevent implantation of a fertilized egg. Emergency contraception is not effective after implantation; therefore, it is not an abortifacient.”⁴

The International Federation of Gynecology & Obstetrics and the International Consortium for Emergency Contraception have issued a joint statement on emergency contraception, including mechanism of action.⁵ This is a good resource for providers and patients. We owe our patients an honest discussion about the current science, from current references and guidelines, so they can make educated decisions based on their own comfort level with emergency contraception.

In Reply: I thank Drs. Kahlenborn and Severs for their comments. Controversy surrounds emergency contraception; thus, it is important to use peer-reviewed, current medical literature to reference mechanism of action. The product label is an unreliable resource, as it was written before current studies that clarified how emergency contraception works. The Noé study concluded that “levonorgestrel emergency contraception does not prevent embryo implantation and therefore cannot be labeled as abortifacient.”¹ They monitored ovulation via ultrasonography and hormonal assays, so they knew in which women ovulation had occurred when emergency contraception was taken. Of those who took it before ovulation, 16 pregnancies were expected and none occurred. When it was taken the day of ovulation or after, 8.7 pregnancies were expected and 8 pregnancies occurred. Because emergency contraception was ineffective after ovulation, a postfertilization effect is unlikely.

Although Drs. Kahlenborn and Severs cited 2004 Croxatto data, they did not cite the 2007 study by Novikova et al,² which concluded that levonorgestrel emergency contraception “has little or no effect on post-ovulation events, but is highly effective when taken before ovulation.”² In this study, when levonorgestrel emergency contraception was taken pre-ovulation, 0 out of 4 expected pregnancies occurred. When it was taken post-ovulation, 3 out of the 3 to 4 expected pregnancies occurred.²

The Frequently Asked Question 114 that Drs. Kahlenborn and Severs cited from the American Congress of Obstetricians and Gynecologists was updated in August 2011 and no longer cites prevention of implantation as a potential mechanism of action. Instead, it reads, “Progestin-only pills are thought to prevent pregnancy mainly by preventing ovulation.” ³ Another ACOG committee opinion, from November 2012, states, “A common misconception is that emergency contraception causes an abortion. Inhibition or delay of ovulation is the principal mechanism of action. Review of evidence suggests that emergency contraception cannot prevent implantation of a fertilized egg. Emergency contraception is not effective after implantation; therefore, it is not an abortifacient.”⁴

The International Federation of Gynecology & Obstetrics and the International Consortium for Emergency Contraception have issued a joint statement on emergency contraception, including mechanism of action.⁵ This is a good resource for providers and patients. We owe our patients an honest discussion about the current science, from current references and guidelines, so they can make educated decisions based on their own comfort level with emergency contraception.

In Reply: I thank Drs. Kahlenborn and Severs for their comments. Controversy surrounds emergency contraception; thus, it is important to use peer-reviewed, current medical literature to reference mechanism of action. The product label is an unreliable resource, as it was written before current studies that clarified how emergency contraception works. The Noé study concluded that “levonorgestrel emergency contraception does not prevent embryo implantation and therefore cannot be labeled as abortifacient.”¹ They monitored ovulation via ultrasonography and hormonal assays, so they knew in which women ovulation had occurred when emergency contraception was taken. Of those who took it before ovulation, 16 pregnancies were expected and none occurred. When it was taken the day of ovulation or after, 8.7 pregnancies were expected and 8 pregnancies occurred. Because emergency contraception was ineffective after ovulation, a postfertilization effect is unlikely.

Although Drs. Kahlenborn and Severs cited 2004 Croxatto data, they did not cite the 2007 study by Novikova et al,² which concluded that levonorgestrel emergency contraception “has little or no effect on post-ovulation events, but is highly effective when taken before ovulation.”² In this study, when levonorgestrel emergency contraception was taken pre-ovulation, 0 out of 4 expected pregnancies occurred. When it was taken post-ovulation, 3 out of the 3 to 4 expected pregnancies occurred.²

The Frequently Asked Question 114 that Drs. Kahlenborn and Severs cited from the American Congress of Obstetricians and Gynecologists was updated in August 2011 and no longer cites prevention of implantation as a potential mechanism of action. Instead, it reads, “Progestin-only pills are thought to prevent pregnancy mainly by preventing ovulation.” ³ Another ACOG committee opinion, from November 2012, states, “A common misconception is that emergency contraception causes an abortion. Inhibition or delay of ovulation is the principal mechanism of action. Review of evidence suggests that emergency contraception cannot prevent implantation of a fertilized egg. Emergency contraception is not effective after implantation; therefore, it is not an abortifacient.”⁴

The International Federation of Gynecology & Obstetrics and the International Consortium for Emergency Contraception have issued a joint statement on emergency contraception, including mechanism of action.⁵ This is a good resource for providers and patients. We owe our patients an honest discussion about the current science, from current references and guidelines, so they can make educated decisions based on their own comfort level with emergency contraception.

To the Editor: In their article “The clinical picture: bilateral adrenal masses” in the December 2012 issue,¹ Drs. Saberi and Esfandiari provide excellent points about adrenal hemorrhage as a differential diagnosis for adrenal masses. However, there are two points worth emphasizing when mentioning this diagnosis, especially in the case they presented.

Drs. Saberi and Esfandiari cryptically mention this patient’s coagulopathy (with thrombocytopenia and a rise in creatinine) and anticoagulation as the probable causes of adrenal hemorrhage. We wonder if a diagnosis of antiphospholipid syndrome (APS) was overlooked. Even though overt Addison disease is reported in only 0.4% of patients with APS² and APS is diagnosed in fewer than 0.5% of all patients with Addison disease,³ we think that in this case, since the patient initially presented with an arterial thrombus in the abdominal aorta, screening for APS would have been warranted.

Second, though it is rare, bilateral adrenal hemorrhage with normal imaging on initial presentation has been described,^2,4 which raises this additional question: Should screening for adrenal insufficiency in a patient with possible APS or other coagulopathy be done early while waiting for repeat computed tomography to reveal hemorrhage? Occasionally, intraparenchymal microhemorrhages may not be recognized by sectional imaging but can nonetheless compromise adrenal function.⁴

To the Editor: In their article “The clinical picture: bilateral adrenal masses” in the December 2012 issue,¹ Drs. Saberi and Esfandiari provide excellent points about adrenal hemorrhage as a differential diagnosis for adrenal masses. However, there are two points worth emphasizing when mentioning this diagnosis, especially in the case they presented.

Drs. Saberi and Esfandiari cryptically mention this patient’s coagulopathy (with thrombocytopenia and a rise in creatinine) and anticoagulation as the probable causes of adrenal hemorrhage. We wonder if a diagnosis of antiphospholipid syndrome (APS) was overlooked. Even though overt Addison disease is reported in only 0.4% of patients with APS² and APS is diagnosed in fewer than 0.5% of all patients with Addison disease,³ we think that in this case, since the patient initially presented with an arterial thrombus in the abdominal aorta, screening for APS would have been warranted.

Second, though it is rare, bilateral adrenal hemorrhage with normal imaging on initial presentation has been described,^2,4 which raises this additional question: Should screening for adrenal insufficiency in a patient with possible APS or other coagulopathy be done early while waiting for repeat computed tomography to reveal hemorrhage? Occasionally, intraparenchymal microhemorrhages may not be recognized by sectional imaging but can nonetheless compromise adrenal function.⁴

To the Editor: In their article “The clinical picture: bilateral adrenal masses” in the December 2012 issue,¹ Drs. Saberi and Esfandiari provide excellent points about adrenal hemorrhage as a differential diagnosis for adrenal masses. However, there are two points worth emphasizing when mentioning this diagnosis, especially in the case they presented.

Drs. Saberi and Esfandiari cryptically mention this patient’s coagulopathy (with thrombocytopenia and a rise in creatinine) and anticoagulation as the probable causes of adrenal hemorrhage. We wonder if a diagnosis of antiphospholipid syndrome (APS) was overlooked. Even though overt Addison disease is reported in only 0.4% of patients with APS² and APS is diagnosed in fewer than 0.5% of all patients with Addison disease,³ we think that in this case, since the patient initially presented with an arterial thrombus in the abdominal aorta, screening for APS would have been warranted.

Second, though it is rare, bilateral adrenal hemorrhage with normal imaging on initial presentation has been described,^2,4 which raises this additional question: Should screening for adrenal insufficiency in a patient with possible APS or other coagulopathy be done early while waiting for repeat computed tomography to reveal hemorrhage? Occasionally, intraparenchymal microhemorrhages may not be recognized by sectional imaging but can nonetheless compromise adrenal function.⁴

To the Editor: The review article “Statins and diabetes: fact, fiction, and clinical implications” ¹ left out one major fact: there are sex-based differences in the statin research results, particularly a higher risk for diabetes in postmenopausal women on statins, with an adjusted hazard ratio of 1.48.² The article promulgated the fiction that statins should be used for primary prevention in women. The first study the author reviewed when discussing the risk of diabetes in “patients” was WOSCOPS—which was an all male study.³

While statin therapy is an effective intervention for secondary prevention of cardiovascular disease in both sexes, it is important to note there is no benefit in rates of all-cause mortality or stroke in women.⁴ The use of statins for primary prevention in women rightly remains controversial.

Any review article on statins or any condition or drug used in both sexes should include some discussion about sex-based differences. While it might be advanced that the increased risk for diabetes, depression, cognitive impairment, and musculoskeletal pain can be justified in secondary prevention in both sexes, that argument is much, much weaker for primary prevention in women, especially since we have evidence showing a reduction in all-cause mortality and primary cardiovascular reduction in women given early postmenopausal hormone therapy.⁵

To the Editor: The review article “Statins and diabetes: fact, fiction, and clinical implications” ¹ left out one major fact: there are sex-based differences in the statin research results, particularly a higher risk for diabetes in postmenopausal women on statins, with an adjusted hazard ratio of 1.48.² The article promulgated the fiction that statins should be used for primary prevention in women. The first study the author reviewed when discussing the risk of diabetes in “patients” was WOSCOPS—which was an all male study.³

While statin therapy is an effective intervention for secondary prevention of cardiovascular disease in both sexes, it is important to note there is no benefit in rates of all-cause mortality or stroke in women.⁴ The use of statins for primary prevention in women rightly remains controversial.

Any review article on statins or any condition or drug used in both sexes should include some discussion about sex-based differences. While it might be advanced that the increased risk for diabetes, depression, cognitive impairment, and musculoskeletal pain can be justified in secondary prevention in both sexes, that argument is much, much weaker for primary prevention in women, especially since we have evidence showing a reduction in all-cause mortality and primary cardiovascular reduction in women given early postmenopausal hormone therapy.⁵

To the Editor: The review article “Statins and diabetes: fact, fiction, and clinical implications” ¹ left out one major fact: there are sex-based differences in the statin research results, particularly a higher risk for diabetes in postmenopausal women on statins, with an adjusted hazard ratio of 1.48.² The article promulgated the fiction that statins should be used for primary prevention in women. The first study the author reviewed when discussing the risk of diabetes in “patients” was WOSCOPS—which was an all male study.³

While statin therapy is an effective intervention for secondary prevention of cardiovascular disease in both sexes, it is important to note there is no benefit in rates of all-cause mortality or stroke in women.⁴ The use of statins for primary prevention in women rightly remains controversial.

Any review article on statins or any condition or drug used in both sexes should include some discussion about sex-based differences. While it might be advanced that the increased risk for diabetes, depression, cognitive impairment, and musculoskeletal pain can be justified in secondary prevention in both sexes, that argument is much, much weaker for primary prevention in women, especially since we have evidence showing a reduction in all-cause mortality and primary cardiovascular reduction in women given early postmenopausal hormone therapy.⁵

In Reply: As Dr. Thacker notes, women are underrepresented in statin clinical trials. This, in addition to the fact that the metaanalyses reviewed did not generally stratify results by sex, makes a detailed discussion of sex-based differences on diabetes incidence and comparative outcomes difficult.

In terms of outcomes, some metaanalyses have found similar reductions of cardiovascular events with statin treatment in men and women, particularly in secondary-prevention populations.^1–3 Even though the cited report from Gutierrez et al⁴ may not have been as inclusive as some other studies, it also demonstrated similar reductions in myocardial infarction, need for intervention, and coronary mortality rates compared with men. The lack of significant reduction in rates of cerebrovascular accidents and all-cause mortality in this study may be a function of the low percentage of women in the analysis (20.6%), the low number of events, and the lack of power. However, the results did trend in a positive direction.

It is true that outcome benefits are harder to demonstrate in primary-prevention populations. However, a meta-analysis by Brugts et al⁵ in 2009 examined 10 placebocontrolled statin trials, including at least 80% of individuals without cardiovascular disease or whose data were reported from a sole primary prevention group. Thirty-four percent of the participants were women. Overall, there was a 12% reduction in mortality, 30% reduction in coronary events, and 19% reduction in cerebrovascular events. Although sex-specific analysis did not show significant reductions in women alone, the directional trends were similar to those in men, and subgroup analysis revealed no heterogeneity in treatment effect by sex, age, or diabetes status.

The meta-analysis from the Cholesterol Treatment Trialists cited in this review included 27 controlled trials and stratified patients by estimated 5-year major vascular event risk⁶; 29% of the patients were women. As expected, annual event rates increased with increasing estimate of risk. Rates of major vascular and major coronary events were reduced by 21% and 30%, respectively. Similar significant proportional reductions were noted in all risk groups, including the lowest two risk groups (< 5% and 5 to < 10%). Although analysis was not stratified by sex, there was a proportionately higher percentage of women (54%) represented in the lowest-risk group, which had a similar relative risk reduction. In the primary-prevention trial JUPITER⁷ in patients with elevated C-reactive protein and low low-density lipoprotein cholesterol levels, rosuvastatin significantly reduced the primary composite end point in women (38% of the study group) by 46%, which was similar to that in the men.^7,8 In the same paper, an additional meta-analysis of exclusively primary prevention trials reported a significant 37% reduction in cardiovascular events.

As for comparable diabetes incidence on statins, it is not accurate to imply that women have a higher risk of developing diabetes than men based only on the Women’s Health Initiative observational analysis—an all-female study with no male comparison arm, without randomization to statins, and in which only 7% of participants at entry were taking the drug in question.

The use of statins in low-risk individuals and in women in particular does remain controversial, partially because of the lack of controlled data and sufficiently powered studies with women. It was not my intent to “promulgate a fiction” that statins should be used in primary prevention in all women, but rather to recommend the use of statins appropriately in at-risk patients after weighing the treatment risks. All therapies, including statin therapy, should be directed toward those who would have the best benefit-risk ratio. To lump together all primary-prevention women, however, is overly simplistic and may result in denying therapy to a patient who may benefit from the intervention. In women as in men, the available data (although imperfect) support statin use with an acceptable risk profile in those at moderate to high risk of subsequent cardiovascular events. Some of these patients would be in the primary prevention classification. Every decision to treat needs to factor in the patient’s overall cardiovascular risk, the likelihood of adverse effects including diabetes, and the patient’s sex.

In Reply: As Dr. Thacker notes, women are underrepresented in statin clinical trials. This, in addition to the fact that the metaanalyses reviewed did not generally stratify results by sex, makes a detailed discussion of sex-based differences on diabetes incidence and comparative outcomes difficult.

In terms of outcomes, some metaanalyses have found similar reductions of cardiovascular events with statin treatment in men and women, particularly in secondary-prevention populations.^1–3 Even though the cited report from Gutierrez et al⁴ may not have been as inclusive as some other studies, it also demonstrated similar reductions in myocardial infarction, need for intervention, and coronary mortality rates compared with men. The lack of significant reduction in rates of cerebrovascular accidents and all-cause mortality in this study may be a function of the low percentage of women in the analysis (20.6%), the low number of events, and the lack of power. However, the results did trend in a positive direction.

It is true that outcome benefits are harder to demonstrate in primary-prevention populations. However, a meta-analysis by Brugts et al⁵ in 2009 examined 10 placebocontrolled statin trials, including at least 80% of individuals without cardiovascular disease or whose data were reported from a sole primary prevention group. Thirty-four percent of the participants were women. Overall, there was a 12% reduction in mortality, 30% reduction in coronary events, and 19% reduction in cerebrovascular events. Although sex-specific analysis did not show significant reductions in women alone, the directional trends were similar to those in men, and subgroup analysis revealed no heterogeneity in treatment effect by sex, age, or diabetes status.

The meta-analysis from the Cholesterol Treatment Trialists cited in this review included 27 controlled trials and stratified patients by estimated 5-year major vascular event risk⁶; 29% of the patients were women. As expected, annual event rates increased with increasing estimate of risk. Rates of major vascular and major coronary events were reduced by 21% and 30%, respectively. Similar significant proportional reductions were noted in all risk groups, including the lowest two risk groups (< 5% and 5 to < 10%). Although analysis was not stratified by sex, there was a proportionately higher percentage of women (54%) represented in the lowest-risk group, which had a similar relative risk reduction. In the primary-prevention trial JUPITER⁷ in patients with elevated C-reactive protein and low low-density lipoprotein cholesterol levels, rosuvastatin significantly reduced the primary composite end point in women (38% of the study group) by 46%, which was similar to that in the men.^7,8 In the same paper, an additional meta-analysis of exclusively primary prevention trials reported a significant 37% reduction in cardiovascular events.

As for comparable diabetes incidence on statins, it is not accurate to imply that women have a higher risk of developing diabetes than men based only on the Women’s Health Initiative observational analysis—an all-female study with no male comparison arm, without randomization to statins, and in which only 7% of participants at entry were taking the drug in question.

The use of statins in low-risk individuals and in women in particular does remain controversial, partially because of the lack of controlled data and sufficiently powered studies with women. It was not my intent to “promulgate a fiction” that statins should be used in primary prevention in all women, but rather to recommend the use of statins appropriately in at-risk patients after weighing the treatment risks. All therapies, including statin therapy, should be directed toward those who would have the best benefit-risk ratio. To lump together all primary-prevention women, however, is overly simplistic and may result in denying therapy to a patient who may benefit from the intervention. In women as in men, the available data (although imperfect) support statin use with an acceptable risk profile in those at moderate to high risk of subsequent cardiovascular events. Some of these patients would be in the primary prevention classification. Every decision to treat needs to factor in the patient’s overall cardiovascular risk, the likelihood of adverse effects including diabetes, and the patient’s sex.

In Reply: As Dr. Thacker notes, women are underrepresented in statin clinical trials. This, in addition to the fact that the metaanalyses reviewed did not generally stratify results by sex, makes a detailed discussion of sex-based differences on diabetes incidence and comparative outcomes difficult.

In terms of outcomes, some metaanalyses have found similar reductions of cardiovascular events with statin treatment in men and women, particularly in secondary-prevention populations.^1–3 Even though the cited report from Gutierrez et al⁴ may not have been as inclusive as some other studies, it also demonstrated similar reductions in myocardial infarction, need for intervention, and coronary mortality rates compared with men. The lack of significant reduction in rates of cerebrovascular accidents and all-cause mortality in this study may be a function of the low percentage of women in the analysis (20.6%), the low number of events, and the lack of power. However, the results did trend in a positive direction.

It is true that outcome benefits are harder to demonstrate in primary-prevention populations. However, a meta-analysis by Brugts et al⁵ in 2009 examined 10 placebocontrolled statin trials, including at least 80% of individuals without cardiovascular disease or whose data were reported from a sole primary prevention group. Thirty-four percent of the participants were women. Overall, there was a 12% reduction in mortality, 30% reduction in coronary events, and 19% reduction in cerebrovascular events. Although sex-specific analysis did not show significant reductions in women alone, the directional trends were similar to those in men, and subgroup analysis revealed no heterogeneity in treatment effect by sex, age, or diabetes status.

The meta-analysis from the Cholesterol Treatment Trialists cited in this review included 27 controlled trials and stratified patients by estimated 5-year major vascular event risk⁶; 29% of the patients were women. As expected, annual event rates increased with increasing estimate of risk. Rates of major vascular and major coronary events were reduced by 21% and 30%, respectively. Similar significant proportional reductions were noted in all risk groups, including the lowest two risk groups (< 5% and 5 to < 10%). Although analysis was not stratified by sex, there was a proportionately higher percentage of women (54%) represented in the lowest-risk group, which had a similar relative risk reduction. In the primary-prevention trial JUPITER⁷ in patients with elevated C-reactive protein and low low-density lipoprotein cholesterol levels, rosuvastatin significantly reduced the primary composite end point in women (38% of the study group) by 46%, which was similar to that in the men.^7,8 In the same paper, an additional meta-analysis of exclusively primary prevention trials reported a significant 37% reduction in cardiovascular events.

As for comparable diabetes incidence on statins, it is not accurate to imply that women have a higher risk of developing diabetes than men based only on the Women’s Health Initiative observational analysis—an all-female study with no male comparison arm, without randomization to statins, and in which only 7% of participants at entry were taking the drug in question.

The use of statins in low-risk individuals and in women in particular does remain controversial, partially because of the lack of controlled data and sufficiently powered studies with women. It was not my intent to “promulgate a fiction” that statins should be used in primary prevention in all women, but rather to recommend the use of statins appropriately in at-risk patients after weighing the treatment risks. All therapies, including statin therapy, should be directed toward those who would have the best benefit-risk ratio. To lump together all primary-prevention women, however, is overly simplistic and may result in denying therapy to a patient who may benefit from the intervention. In women as in men, the available data (although imperfect) support statin use with an acceptable risk profile in those at moderate to high risk of subsequent cardiovascular events. Some of these patients would be in the primary prevention classification. Every decision to treat needs to factor in the patient’s overall cardiovascular risk, the likelihood of adverse effects including diabetes, and the patient’s sex.

Glenn J. Lesser, MD, Doug Case, PhD, Nancy Stark, RN, PhD, et al

Background Coenzyme Q₁₀ (CoQ₁₀) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits.

Objectives We performed a randomized, double-blind, placebo-controlled study of oral CoQ₁₀ in female breast cancer patients with the primary objective of determining CoQ₁₀ ’s effects on self-reported fatigue, depression, and quality of life (QOL).

Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oralsupplements of 300 mg CoQ₁₀ or placebo, each combined with 300 IU vitamin E, divided into 3 daily doses. Treatment wascontinued for 24 weeks. Blood tests, QOL measures, and levels of plasma CoQ₁₀ and vitamin E were obtained at baseline and at 8,16, and 24 weeks. Mixed-effects models were used to assess treatment differences in outcomes over time.

Results Between September 2004 and March 2009, 236 women were enrolled. Treatment arms were well balanced with respect to age(range, 28-85 years), pathologic stage (stage 0, 91%; stage I, 8%; stage II, 1%), ethnicity (white, 87%; black, 11%; Hispanic, 2%), and planned therapy. Baseline CoQ₁₀ levels in the CoQ₁₀ and placebo arms were 0.70 and 0.73 g/mL, respectively; the 24-week CoQ₁₀ levels were 1.83 and 0.79g/mL, respectively. There were no significant differences between the CoQ₁₀ and placebo arms at 24 weeks for scores on the Profile of Mood States–Fatigue questionnaire (least squares means, 7.08 vs 8.24, P = .257), the Functional Assessment of Chronic Illness Therapy–Fatigue tool (37.6 vs 37.6, P = .965), the Functional Assessment of Cancer Therapy–Breast Cancer instrument (111.9 vs 110.4, P = .577), or the Center for Epidemiologic Studies–Depression scale (11.6 vs 12.3, P = .632).

Conclusions Supplementation with conventional doses of CoQ₁₀ led to sustained increases in plasma CoQ₁₀ levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Glenn J. Lesser, MD, Doug Case, PhD, Nancy Stark, RN, PhD, et al

Background Coenzyme Q₁₀ (CoQ₁₀) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits.

Objectives We performed a randomized, double-blind, placebo-controlled study of oral CoQ₁₀ in female breast cancer patients with the primary objective of determining CoQ₁₀ ’s effects on self-reported fatigue, depression, and quality of life (QOL).

Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oralsupplements of 300 mg CoQ₁₀ or placebo, each combined with 300 IU vitamin E, divided into 3 daily doses. Treatment wascontinued for 24 weeks. Blood tests, QOL measures, and levels of plasma CoQ₁₀ and vitamin E were obtained at baseline and at 8,16, and 24 weeks. Mixed-effects models were used to assess treatment differences in outcomes over time.

Results Between September 2004 and March 2009, 236 women were enrolled. Treatment arms were well balanced with respect to age(range, 28-85 years), pathologic stage (stage 0, 91%; stage I, 8%; stage II, 1%), ethnicity (white, 87%; black, 11%; Hispanic, 2%), and planned therapy. Baseline CoQ₁₀ levels in the CoQ₁₀ and placebo arms were 0.70 and 0.73 g/mL, respectively; the 24-week CoQ₁₀ levels were 1.83 and 0.79g/mL, respectively. There were no significant differences between the CoQ₁₀ and placebo arms at 24 weeks for scores on the Profile of Mood States–Fatigue questionnaire (least squares means, 7.08 vs 8.24, P = .257), the Functional Assessment of Chronic Illness Therapy–Fatigue tool (37.6 vs 37.6, P = .965), the Functional Assessment of Cancer Therapy–Breast Cancer instrument (111.9 vs 110.4, P = .577), or the Center for Epidemiologic Studies–Depression scale (11.6 vs 12.3, P = .632).

Conclusions Supplementation with conventional doses of CoQ₁₀ led to sustained increases in plasma CoQ₁₀ levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Glenn J. Lesser, MD, Doug Case, PhD, Nancy Stark, RN, PhD, et al

Background Coenzyme Q₁₀ (CoQ₁₀) is a common antioxidant supplement with known cardioprotective effects and potential anticancer benefits.

Objectives We performed a randomized, double-blind, placebo-controlled study of oral CoQ₁₀ in female breast cancer patients with the primary objective of determining CoQ₁₀ ’s effects on self-reported fatigue, depression, and quality of life (QOL).

Methods Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oralsupplements of 300 mg CoQ₁₀ or placebo, each combined with 300 IU vitamin E, divided into 3 daily doses. Treatment wascontinued for 24 weeks. Blood tests, QOL measures, and levels of plasma CoQ₁₀ and vitamin E were obtained at baseline and at 8,16, and 24 weeks. Mixed-effects models were used to assess treatment differences in outcomes over time.

Results Between September 2004 and March 2009, 236 women were enrolled. Treatment arms were well balanced with respect to age(range, 28-85 years), pathologic stage (stage 0, 91%; stage I, 8%; stage II, 1%), ethnicity (white, 87%; black, 11%; Hispanic, 2%), and planned therapy. Baseline CoQ₁₀ levels in the CoQ₁₀ and placebo arms were 0.70 and 0.73 g/mL, respectively; the 24-week CoQ₁₀ levels were 1.83 and 0.79g/mL, respectively. There were no significant differences between the CoQ₁₀ and placebo arms at 24 weeks for scores on the Profile of Mood States–Fatigue questionnaire (least squares means, 7.08 vs 8.24, P = .257), the Functional Assessment of Chronic Illness Therapy–Fatigue tool (37.6 vs 37.6, P = .965), the Functional Assessment of Cancer Therapy–Breast Cancer instrument (111.9 vs 110.4, P = .577), or the Center for Epidemiologic Studies–Depression scale (11.6 vs 12.3, P = .632).

Conclusions Supplementation with conventional doses of CoQ₁₀ led to sustained increases in plasma CoQ₁₀ levels but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment.

*For a PDF of the full article, click on the link to the left of this introduction.

Background The impact of arm morbidity following breast cancer surgery on patient-observed changes in daily functioningand health-related quality of life (HRQoL) has not been well-studied.

Objective To examine the association of objective measures such as range of motion (ROM) and lymphedema, with patient-reported outcomes (PROs) in the arm and breast, upper  extremity function, activities, and HRQoL.

Methods The National Surgical Adjuvant Breast and Bowel Project Protocol B-32 was a randomized trial comparingsentinel node resection (SNR) with axillary dissection (AD) in women with node-negative breast cancer. ROM and armvolume were measured objectively.  PROs included symptoms; arm function; limitations in social, recreational, occupational,and other regular activities; and a global index of HRQoL. Statistical methods included cross-tabulations and multivariablelinear regression models.

Results In all, 744 women provided at least 1 postsurgery assessment. About one-third of the patients experienced arm mobility restrictions. A similar number of patients avoided the use of the arm 6 months after surgery. Limitations in work and other regular activities were reported by about a quarter of the patients. In this multivariable analysis, arm mobility and sensory neuropathy were predictors of patient-reported arm function and overall HRQoL. Predictors for activity limitations also included side of surgery (dominant vs nondominant). Edema was not significant after adjustment for sensory neuropathy and ROM.

Limitations Arm mobility and edema were measured simultaneously only once during the follow-up (6 months).

Conclusion Clinical measures of sensory neuropathy and restrictions in arm mobility following breast cancer surgery are associated with self-reported limitations in activity and reductions in overall HRQoL.

Click on the PDF icon at the top of this introduction to read the full article.

Background The impact of arm morbidity following breast cancer surgery on patient-observed changes in daily functioningand health-related quality of life (HRQoL) has not been well-studied.

Objective To examine the association of objective measures such as range of motion (ROM) and lymphedema, with patient-reported outcomes (PROs) in the arm and breast, upper  extremity function, activities, and HRQoL.

Methods The National Surgical Adjuvant Breast and Bowel Project Protocol B-32 was a randomized trial comparingsentinel node resection (SNR) with axillary dissection (AD) in women with node-negative breast cancer. ROM and armvolume were measured objectively.  PROs included symptoms; arm function; limitations in social, recreational, occupational,and other regular activities; and a global index of HRQoL. Statistical methods included cross-tabulations and multivariablelinear regression models.

Results In all, 744 women provided at least 1 postsurgery assessment. About one-third of the patients experienced arm mobility restrictions. A similar number of patients avoided the use of the arm 6 months after surgery. Limitations in work and other regular activities were reported by about a quarter of the patients. In this multivariable analysis, arm mobility and sensory neuropathy were predictors of patient-reported arm function and overall HRQoL. Predictors for activity limitations also included side of surgery (dominant vs nondominant). Edema was not significant after adjustment for sensory neuropathy and ROM.

Limitations Arm mobility and edema were measured simultaneously only once during the follow-up (6 months).

Conclusion Clinical measures of sensory neuropathy and restrictions in arm mobility following breast cancer surgery are associated with self-reported limitations in activity and reductions in overall HRQoL.

Click on the PDF icon at the top of this introduction to read the full article.

Background The impact of arm morbidity following breast cancer surgery on patient-observed changes in daily functioningand health-related quality of life (HRQoL) has not been well-studied.

Objective To examine the association of objective measures such as range of motion (ROM) and lymphedema, with patient-reported outcomes (PROs) in the arm and breast, upper  extremity function, activities, and HRQoL.

Methods The National Surgical Adjuvant Breast and Bowel Project Protocol B-32 was a randomized trial comparingsentinel node resection (SNR) with axillary dissection (AD) in women with node-negative breast cancer. ROM and armvolume were measured objectively.  PROs included symptoms; arm function; limitations in social, recreational, occupational,and other regular activities; and a global index of HRQoL. Statistical methods included cross-tabulations and multivariablelinear regression models.

Results In all, 744 women provided at least 1 postsurgery assessment. About one-third of the patients experienced arm mobility restrictions. A similar number of patients avoided the use of the arm 6 months after surgery. Limitations in work and other regular activities were reported by about a quarter of the patients. In this multivariable analysis, arm mobility and sensory neuropathy were predictors of patient-reported arm function and overall HRQoL. Predictors for activity limitations also included side of surgery (dominant vs nondominant). Edema was not significant after adjustment for sensory neuropathy and ROM.

Limitations Arm mobility and edema were measured simultaneously only once during the follow-up (6 months).

Conclusion Clinical measures of sensory neuropathy and restrictions in arm mobility following breast cancer surgery are associated with self-reported limitations in activity and reductions in overall HRQoL.

Click on the PDF icon at the top of this introduction to read the full article.

George Dranitsaris, BPharm, PhD, Nathaniel Bouganim, MD, Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, and Mark Clemons, MD

Background Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severechemotherapy-induced nausea and vomiting (CINV) (grade 2). We previously developed chemotherapy cycle–based risk predictive models forgrade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models andassociated scoring systems is described.

Objective Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate tosevere CINV.

Methods Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used tocompare the occurrence of grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

Results Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62– 0.77; delayed, AUROC = 0.75, 95% CI, 0.69 – 0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop grade 2 acute and delayed CINV than were those identified as low risk.

Conclusion This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

*For a PDF of the full article, click on the link to the left of this introduction.

George Dranitsaris, BPharm, PhD, Nathaniel Bouganim, MD, Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, and Mark Clemons, MD

Background Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severechemotherapy-induced nausea and vomiting (CINV) (grade 2). We previously developed chemotherapy cycle–based risk predictive models forgrade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models andassociated scoring systems is described.

Objective Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate tosevere CINV.

Methods Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used tocompare the occurrence of grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

Results Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62– 0.77; delayed, AUROC = 0.75, 95% CI, 0.69 – 0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop grade 2 acute and delayed CINV than were those identified as low risk.

Conclusion This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

*For a PDF of the full article, click on the link to the left of this introduction.

George Dranitsaris, BPharm, PhD, Nathaniel Bouganim, MD, Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, and Mark Clemons, MD

Background Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severechemotherapy-induced nausea and vomiting (CINV) (grade 2). We previously developed chemotherapy cycle–based risk predictive models forgrade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models andassociated scoring systems is described.

Objective Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate tosevere CINV.

Methods Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used tocompare the occurrence of grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

Results Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62– 0.77; delayed, AUROC = 0.75, 95% CI, 0.69 – 0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop grade 2 acute and delayed CINV than were those identified as low risk.

Conclusion This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

*For a PDF of the full article, click on the link to the left of this introduction.

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution’s practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic.

Click on the PDF icon at the top of this introduction to read the full article.

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution’s practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic.

Click on the PDF icon at the top of this introduction to read the full article.

Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution’s practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic.

Click on the PDF icon at the top of this introduction to read the full article.

What are the ethical responsibilities of the medical staff (doctors, nurses, social workers, and chaplains) regarding thepreservation of meaningful life for their patients who are approaching the end of life (EOL)? In particular, what is the staff’sethical responsibility to initiate a conversation with their patient regarding palliative care? By subjecting traditional Jewish teachings to an ethical analysis and then exploring the underlying universal principles, we will suggest a general ethical duty toinform patients of the different care options, especially in a manner that preserves hope. The principle that we can derive from Jewish bioethics teaches that the medical staff has a responsibility to help our patients live in a way that is consistent with how they understand their task or responsibility in life. For some patients, the best way to preserve a meaningful life in which they can fulfill their sense of purpose in the time that remains is to focus on palliation. For this reason, although palliative and supportive care are provided from the time of diagnosis, it is critical we make sure our patients realize that they have the opportunity to make a decision between either pursuing additional active treatments or choosing to focus primarily on palliative therapies to maximize quality of life. The Jewish tradition and our experience in spiritual care suggest the importance of helping patients preserve hope while, simultaneously, honestly acknowledging their situation. Staff members can play a vital role in helping patients make the most of this new period of their lives.

Click on the PDF icon at the top of this introduction to read the full article.

What are the ethical responsibilities of the medical staff (doctors, nurses, social workers, and chaplains) regarding thepreservation of meaningful life for their patients who are approaching the end of life (EOL)? In particular, what is the staff’sethical responsibility to initiate a conversation with their patient regarding palliative care? By subjecting traditional Jewish teachings to an ethical analysis and then exploring the underlying universal principles, we will suggest a general ethical duty toinform patients of the different care options, especially in a manner that preserves hope. The principle that we can derive from Jewish bioethics teaches that the medical staff has a responsibility to help our patients live in a way that is consistent with how they understand their task or responsibility in life. For some patients, the best way to preserve a meaningful life in which they can fulfill their sense of purpose in the time that remains is to focus on palliation. For this reason, although palliative and supportive care are provided from the time of diagnosis, it is critical we make sure our patients realize that they have the opportunity to make a decision between either pursuing additional active treatments or choosing to focus primarily on palliative therapies to maximize quality of life. The Jewish tradition and our experience in spiritual care suggest the importance of helping patients preserve hope while, simultaneously, honestly acknowledging their situation. Staff members can play a vital role in helping patients make the most of this new period of their lives.

Click on the PDF icon at the top of this introduction to read the full article.

What are the ethical responsibilities of the medical staff (doctors, nurses, social workers, and chaplains) regarding thepreservation of meaningful life for their patients who are approaching the end of life (EOL)? In particular, what is the staff’sethical responsibility to initiate a conversation with their patient regarding palliative care? By subjecting traditional Jewish teachings to an ethical analysis and then exploring the underlying universal principles, we will suggest a general ethical duty toinform patients of the different care options, especially in a manner that preserves hope. The principle that we can derive from Jewish bioethics teaches that the medical staff has a responsibility to help our patients live in a way that is consistent with how they understand their task or responsibility in life. For some patients, the best way to preserve a meaningful life in which they can fulfill their sense of purpose in the time that remains is to focus on palliation. For this reason, although palliative and supportive care are provided from the time of diagnosis, it is critical we make sure our patients realize that they have the opportunity to make a decision between either pursuing additional active treatments or choosing to focus primarily on palliative therapies to maximize quality of life. The Jewish tradition and our experience in spiritual care suggest the importance of helping patients preserve hope while, simultaneously, honestly acknowledging their situation. Staff members can play a vital role in helping patients make the most of this new period of their lives.

Click on the PDF icon at the top of this introduction to read the full article.

Kevin P. High, MD, MS; Doug Case, PhD;  MD, David Hurd, MD; Bayard Powell, MD; Glenn Lesser, MD; Ann R. Falsey, MD; Robert Siegel, MD; Joanna Metzner-Sadurski, MD; John C. Krauss, MD; Bernard Chinnasami, MD, George Sanders, MD, Steven Rousey, MD, Edward G. Shaw, MD

*For a PDF of the full article and accompanying commentary by Paul Sloan, click on the links to the left of this introduction.

Kevin P. High, MD, MS; Doug Case, PhD;  MD, David Hurd, MD; Bayard Powell, MD; Glenn Lesser, MD; Ann R. Falsey, MD; Robert Siegel, MD; Joanna Metzner-Sadurski, MD; John C. Krauss, MD; Bernard Chinnasami, MD, George Sanders, MD, Steven Rousey, MD, Edward G. Shaw, MD

*For a PDF of the full article and accompanying commentary by Paul Sloan, click on the links to the left of this introduction.

Kevin P. High, MD, MS; Doug Case, PhD;  MD, David Hurd, MD; Bayard Powell, MD; Glenn Lesser, MD; Ann R. Falsey, MD; Robert Siegel, MD; Joanna Metzner-Sadurski, MD; John C. Krauss, MD; Bernard Chinnasami, MD, George Sanders, MD, Steven Rousey, MD, Edward G. Shaw, MD

*For a PDF of the full article and accompanying commentary by Paul Sloan, click on the links to the left of this introduction.