Letters To The Editor

In Reply: We thank Dr. Davidson for his comments. Indeed, the teaching points may appear inconsistent with the actual patient journey in this case. In the real world, physicians from different teams and specialties are involved in the care of a patient, and medical practice may not strictly adhere to guidelines.

In question 1, the emergency department physician decided to proceed with computed tomographic pulmonary angiography to rule out pulmonary embolism. Based on best practice guidelines, pulmonary angiography was not indicated, as the clinical pretest probability of pulmonary embolism was low, supported by the patient’s negative D-dimer test. When we wrote the article, as we already had the scan, we used it to support the learning points in terms of findings on computed tomography at the early stage of a developing empyema, and also to support that the scan was in fact not indicated (not the other way around).

As for question 2, specific data-driven guidelines do not exist on how best to manage patients with bronchopneumonia with an early evolving parapneumonic effusion. In the text that follows question 2, we stated that management as an inpatient or outpatient would have been reasonable. Although we considered the patient at low risk for a poor outcome, we offered inpatient admission at the time for better control of his severe pleuritic pain (this could have been made clearer in the text), as well as close monitoring of his evolving parapneumonic effusion, and we do not believe that this contradicts the teaching points of this case.

In Reply: We thank Dr. Davidson for his comments. Indeed, the teaching points may appear inconsistent with the actual patient journey in this case. In the real world, physicians from different teams and specialties are involved in the care of a patient, and medical practice may not strictly adhere to guidelines.

In question 1, the emergency department physician decided to proceed with computed tomographic pulmonary angiography to rule out pulmonary embolism. Based on best practice guidelines, pulmonary angiography was not indicated, as the clinical pretest probability of pulmonary embolism was low, supported by the patient’s negative D-dimer test. When we wrote the article, as we already had the scan, we used it to support the learning points in terms of findings on computed tomography at the early stage of a developing empyema, and also to support that the scan was in fact not indicated (not the other way around).

As for question 2, specific data-driven guidelines do not exist on how best to manage patients with bronchopneumonia with an early evolving parapneumonic effusion. In the text that follows question 2, we stated that management as an inpatient or outpatient would have been reasonable. Although we considered the patient at low risk for a poor outcome, we offered inpatient admission at the time for better control of his severe pleuritic pain (this could have been made clearer in the text), as well as close monitoring of his evolving parapneumonic effusion, and we do not believe that this contradicts the teaching points of this case.

In Reply: We thank Dr. Davidson for his comments. Indeed, the teaching points may appear inconsistent with the actual patient journey in this case. In the real world, physicians from different teams and specialties are involved in the care of a patient, and medical practice may not strictly adhere to guidelines.

In question 1, the emergency department physician decided to proceed with computed tomographic pulmonary angiography to rule out pulmonary embolism. Based on best practice guidelines, pulmonary angiography was not indicated, as the clinical pretest probability of pulmonary embolism was low, supported by the patient’s negative D-dimer test. When we wrote the article, as we already had the scan, we used it to support the learning points in terms of findings on computed tomography at the early stage of a developing empyema, and also to support that the scan was in fact not indicated (not the other way around).

As for question 2, specific data-driven guidelines do not exist on how best to manage patients with bronchopneumonia with an early evolving parapneumonic effusion. In the text that follows question 2, we stated that management as an inpatient or outpatient would have been reasonable. Although we considered the patient at low risk for a poor outcome, we offered inpatient admission at the time for better control of his severe pleuritic pain (this could have been made clearer in the text), as well as close monitoring of his evolving parapneumonic effusion, and we do not believe that this contradicts the teaching points of this case.

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

We appreciate the query by Drs. Douglas and Wilson. We hereby supply additional information that is critical for creating and administering sustainable staffing models.

For programs with a census cap, the majority cited 16 or fewer patients as the trigger for that cap. Nearly all programs with back-up used a census of 16 or fewer. Over 80% of programs cited a “safe 7 am census” as 16 or fewer. These data suggest that a census over 16 is appropriate to trigger additional clinical support.

Regarding clinical weighting of nights, nighttime shifts were often more heavily weighted than day shifts, but approaches to weighting varied and have not been validated. Alternate staffing models for overnight pager calls varied greatly by individual program.

This is a time of significant growth for pediatric hospital medicine, and national workforce data are essential to hospitalists, administrators, and most importantly, patients. Our study¹ provides pediatric hospital medicine leaders with data for discussions regarding appropriate FTE and staffing model considerations. The insights generated by our study are particularly relevant in expanding programs and solving problems related to recruitment and retention.

Disclosures

The authors have nothing to disclose.

We appreciate the query by Drs. Douglas and Wilson. We hereby supply additional information that is critical for creating and administering sustainable staffing models.

For programs with a census cap, the majority cited 16 or fewer patients as the trigger for that cap. Nearly all programs with back-up used a census of 16 or fewer. Over 80% of programs cited a “safe 7 am census” as 16 or fewer. These data suggest that a census over 16 is appropriate to trigger additional clinical support.

Regarding clinical weighting of nights, nighttime shifts were often more heavily weighted than day shifts, but approaches to weighting varied and have not been validated. Alternate staffing models for overnight pager calls varied greatly by individual program.

This is a time of significant growth for pediatric hospital medicine, and national workforce data are essential to hospitalists, administrators, and most importantly, patients. Our study¹ provides pediatric hospital medicine leaders with data for discussions regarding appropriate FTE and staffing model considerations. The insights generated by our study are particularly relevant in expanding programs and solving problems related to recruitment and retention.

Disclosures

The authors have nothing to disclose.

We appreciate the query by Drs. Douglas and Wilson. We hereby supply additional information that is critical for creating and administering sustainable staffing models.

For programs with a census cap, the majority cited 16 or fewer patients as the trigger for that cap. Nearly all programs with back-up used a census of 16 or fewer. Over 80% of programs cited a “safe 7 am census” as 16 or fewer. These data suggest that a census over 16 is appropriate to trigger additional clinical support.

Regarding clinical weighting of nights, nighttime shifts were often more heavily weighted than day shifts, but approaches to weighting varied and have not been validated. Alternate staffing models for overnight pager calls varied greatly by individual program.

This is a time of significant growth for pediatric hospital medicine, and national workforce data are essential to hospitalists, administrators, and most importantly, patients. Our study¹ provides pediatric hospital medicine leaders with data for discussions regarding appropriate FTE and staffing model considerations. The insights generated by our study are particularly relevant in expanding programs and solving problems related to recruitment and retention.

Disclosures

The authors have nothing to disclose.

As leaders of a new Pediatric Hospital Medicine program in New York City, we were pleased to read the Brief Report from Dr. Fromme and colleagues, “Pediatric Hospitalist Workload and Sustainability in University-Based Programs: Results from a National Interview-Based Survey.”

Although the study has greatly assisted us in developing our program, the manuscript lacked some data necessary for workforce planning. The authors report census caps for a majority of programs, but neither the actual number of patients in each cap nor whether programs with caps reported an association with patient safety or program sustainability. In addition, although overnight pager calls were calculated in median hours, there were no data on whether nights were weighted or alternate staffing models were used for overnight pager calls.

While the article will help guide our field’s continued understanding of our workforce, without additional detailed data, we found that we were unable to apply staffing models practically in the real world to our new program. Pediatric Hospital Medicine is one of the fastest growing fields in medicine; however, support of new programs and sustainability of existing ones, require benchmark details to create proposals that are acceptable to both hospital and university administrators while maintaining workforce sustainability.

Disclosures

Drs. Douglas and Wilson have nothing to disclose.

As leaders of a new Pediatric Hospital Medicine program in New York City, we were pleased to read the Brief Report from Dr. Fromme and colleagues, “Pediatric Hospitalist Workload and Sustainability in University-Based Programs: Results from a National Interview-Based Survey.”

Although the study has greatly assisted us in developing our program, the manuscript lacked some data necessary for workforce planning. The authors report census caps for a majority of programs, but neither the actual number of patients in each cap nor whether programs with caps reported an association with patient safety or program sustainability. In addition, although overnight pager calls were calculated in median hours, there were no data on whether nights were weighted or alternate staffing models were used for overnight pager calls.

While the article will help guide our field’s continued understanding of our workforce, without additional detailed data, we found that we were unable to apply staffing models practically in the real world to our new program. Pediatric Hospital Medicine is one of the fastest growing fields in medicine; however, support of new programs and sustainability of existing ones, require benchmark details to create proposals that are acceptable to both hospital and university administrators while maintaining workforce sustainability.

Disclosures

Drs. Douglas and Wilson have nothing to disclose.

As leaders of a new Pediatric Hospital Medicine program in New York City, we were pleased to read the Brief Report from Dr. Fromme and colleagues, “Pediatric Hospitalist Workload and Sustainability in University-Based Programs: Results from a National Interview-Based Survey.”

Although the study has greatly assisted us in developing our program, the manuscript lacked some data necessary for workforce planning. The authors report census caps for a majority of programs, but neither the actual number of patients in each cap nor whether programs with caps reported an association with patient safety or program sustainability. In addition, although overnight pager calls were calculated in median hours, there were no data on whether nights were weighted or alternate staffing models were used for overnight pager calls.

While the article will help guide our field’s continued understanding of our workforce, without additional detailed data, we found that we were unable to apply staffing models practically in the real world to our new program. Pediatric Hospital Medicine is one of the fastest growing fields in medicine; however, support of new programs and sustainability of existing ones, require benchmark details to create proposals that are acceptable to both hospital and university administrators while maintaining workforce sustainability.

Disclosures

Drs. Douglas and Wilson have nothing to disclose.

Vaginal approach is the most cost-effective route

I applaud Drs. Kotha and Sanfilippo for addressing the “elephant in the room.” At the hospitals where I work, surgeons pay little or no attention to the cost of the disposables and operating room time used for their laparoscopic procedures. I believe the authors were remiss, though, to not at least mention the most minimally invasive approach to hysterectomy—the vaginal approach—which is by far the most cost-effective and safest route.

Thomas Powers, MD

Arcadia, California

Drs. Kotha and Sanfilippo respond

We appreciate Dr. Powers’ comments regarding our article on cost-conscious choices for minimally invasive gynecologic surgery. Indeed, he provides an important point. As the article’s overall focus, however, was on minimally invasive gynecologic surgery, we did not include a comparison with either abdominal or vaginal hysterectomy. Of interest, Warren and colleagues conducted a retrospective analysis of claims data in which expenditures for minimally invasive procedures (MIP) were compared with those of vaginal hysterectomy.¹ For 15,404 patients who underwent surgery, costs were compared between MIP and abdominal as well as vaginal hysterectomy. Costs were as follows:

• abdominal hysterectomy, $12,086
• MIP, $10,868
• vaginal hysterectomy, $9,544.

Vaginal hysterectomy cost was statistically significantly less (P<.05) compared with other methods. The authors concluded that the laparoscopic approach should be considered when the option of an abdominal versus laparoscopic procedure is entertained. For the gynecologic surgeon considering a laparoscopic approach, the information we provided in our article merits strong consideration.

Vaginal approach is the most cost-effective route

I applaud Drs. Kotha and Sanfilippo for addressing the “elephant in the room.” At the hospitals where I work, surgeons pay little or no attention to the cost of the disposables and operating room time used for their laparoscopic procedures. I believe the authors were remiss, though, to not at least mention the most minimally invasive approach to hysterectomy—the vaginal approach—which is by far the most cost-effective and safest route.

Thomas Powers, MD

Arcadia, California

Drs. Kotha and Sanfilippo respond

We appreciate Dr. Powers’ comments regarding our article on cost-conscious choices for minimally invasive gynecologic surgery. Indeed, he provides an important point. As the article’s overall focus, however, was on minimally invasive gynecologic surgery, we did not include a comparison with either abdominal or vaginal hysterectomy. Of interest, Warren and colleagues conducted a retrospective analysis of claims data in which expenditures for minimally invasive procedures (MIP) were compared with those of vaginal hysterectomy.¹ For 15,404 patients who underwent surgery, costs were compared between MIP and abdominal as well as vaginal hysterectomy. Costs were as follows:

• abdominal hysterectomy, $12,086
• MIP, $10,868
• vaginal hysterectomy, $9,544.

Vaginal hysterectomy cost was statistically significantly less (P<.05) compared with other methods. The authors concluded that the laparoscopic approach should be considered when the option of an abdominal versus laparoscopic procedure is entertained. For the gynecologic surgeon considering a laparoscopic approach, the information we provided in our article merits strong consideration.

Vaginal approach is the most cost-effective route

I applaud Drs. Kotha and Sanfilippo for addressing the “elephant in the room.” At the hospitals where I work, surgeons pay little or no attention to the cost of the disposables and operating room time used for their laparoscopic procedures. I believe the authors were remiss, though, to not at least mention the most minimally invasive approach to hysterectomy—the vaginal approach—which is by far the most cost-effective and safest route.

Thomas Powers, MD

Arcadia, California

Drs. Kotha and Sanfilippo respond

We appreciate Dr. Powers’ comments regarding our article on cost-conscious choices for minimally invasive gynecologic surgery. Indeed, he provides an important point. As the article’s overall focus, however, was on minimally invasive gynecologic surgery, we did not include a comparison with either abdominal or vaginal hysterectomy. Of interest, Warren and colleagues conducted a retrospective analysis of claims data in which expenditures for minimally invasive procedures (MIP) were compared with those of vaginal hysterectomy.¹ For 15,404 patients who underwent surgery, costs were compared between MIP and abdominal as well as vaginal hysterectomy. Costs were as follows:

• abdominal hysterectomy, $12,086
• MIP, $10,868
• vaginal hysterectomy, $9,544.

Vaginal hysterectomy cost was statistically significantly less (P<.05) compared with other methods. The authors concluded that the laparoscopic approach should be considered when the option of an abdominal versus laparoscopic procedure is entertained. For the gynecologic surgeon considering a laparoscopic approach, the information we provided in our article merits strong consideration.

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Dienogest as an option for endometriosis pain

For treatment of endometriosis-related pain, what about the drug dienogest and the cyclic oral contraceptive Qlaira, which contains dienogest?

Chow Kah Kiong, MBBS
Singapore

-- 

--

Norethindrone’s conversion to ethinyl estradiol

Dr. Barbieri’s editorial on the medical treatment of endometriosis is excellent! Does norethindrone acetate metabolize to ethinyl estradiol in a higher percentage when the dose is higher, or is it still 1%? We were taught that at doses of greater than 15 mg daily, norethindrone can contribute significant amounts of estrogen.

Lauren Barnes, MD
Albuquerque, New Mexico

Endometriosis is a surgical, not a medical, disease

I read with some dismay Dr. Barbieri’s editorial on medical treatment of endometriosis. As a long-time disciple of the eminent Dr. David Redwine, I have dedicated my practice focus over the past 28 years to minimally invasive curative solutions to many gynecologic problems. The data on the histology, qualitative hormonal differences, and inconsistent and poor long-term response of endometriosis to traditional hormonal suppressive therapies falls strongly in favor of complete and thorough laparoscopic excision—not “biopsy”—as the only truly curative treatment, certainly not medical therapy. Endometriosis is a surgical disease. The experience of the dedicated few in our field who have taken the time and effort to become experts in excision (not ablation) of endometriosis bears this out.

The tragedy is that the only Current Procedural Terminology code that is usable for reimbursement is 58662. Sadly, this code was assigned a resource-based relative value scale “value” many years ago, when the operation consisted of putting a scope in the abdomen and taking a sampling biopsy (which took all of 10 minutes). Of course, we know that a prolonged, delicate procedure requiring retroperitoneal dissection, ureterolysis, excision of deeply infiltrating rectovaginal septum endometriosis, and discoid or segmental bowel resection requires the kind of surgical expertise developed only by those who put in the time and effort to get good at this type of surgery. The majority of ObGyns who have a full obstetric practice and low surgical volumes simply are not going to struggle in the operating room over the many cases that it takes to become good, and safe, at this procedure only to receive an insulting reimbursement.

It is emblematic of this travesty that many of the best minimally invasive surgery practitioners do not accept insurance or other thirdparty payment such as Medicaid as they would otherwise not cover their overhead.

Putting premenopausal women into a severely hypoestrogenic state with medication is cruel and, even worse, does not cure the disease.

Balanced information on surgical management should have been presented in the article. And physicians who are not capable of proper laparoscopic excision should refer the patient.

Hugo Ribot, MD
Cartersville, Georgia

Continue to: Dr. Barbieri responds

I thank Drs. Chow, Barnes, and Ribot for their interest in my recent editorial on the medical treatment of endometriosis. I agree with Dr. Chow that dienogest, a synthetic progestin, is effective in the treatment of pelvic pain caused by endometriosis. In one observational study, norethindrone acetate 2.5 mg daily and dienogest 2 mg daily had similar efficacy in the treatment of pelvic pain. Dienogest treatment was associated with fewer side effects but was much more expensive than norethindrone acetate.¹ The US Food and Drug Administration has approved a combination estradiol- progestin pill (Natazia, Qlaira) as a contraceptive, and I have occasionally used this medication in my practice for women with pelvic pain caused by endometriosis. Dienogest monotherapy is not available in the United States.

Dr. Barnes reminds us that norethindrone is a substrate for the aromatase enzyme system and can be converted to ethinyl estradiol.² The conversion occurs at a very low rate, likely less than 0.4%.³ At a norethindrone acetate dose of 5 mg daily, aromatization would result in the production of less than 2 μg of ethinyl estradiol daily.

Dr. Ribot advocates for surgery as the primary treatment of pelvic pain caused by endometriosis. I agree with Dr. Ribot that, for severe pain caused by deep infiltrating endometriosis, surgery is an optimal approach. However, for women with pelvic pain and Stage I endometriosis, hormonal treatment after initial surgical diagnosis and treatment reduces pain recurrence and repetitive surgical procedures.⁴

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

To the Editor: In their article on men’s health,¹Chaitoff and colleagues present the scenario of a 60-year-old patient, with no other history given, whose recent screening prostate-specific antigen (PSA) level was 5.1 ng/mL, and who asks his doctor:

1. Should I have agreed to the screening?
2. How effective is the screening?
3. What are the next steps?

These questions are consistent with the patient having read the latest US Preventive Services Task Force (USPSTF) report on PSA screening, which states: “Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results…”²

I would tell the patient that he can expect greater benefit from PSA screening than reported by the USPSTF simply by adhering to the screening protocol. Intention-to-treat analysis applied to the trial results diminished the apparent benefits of PSA screening by counting fatal prostate cancers experienced by nonadherent study participants as screening failures.³ In other words, screening works better in those who actually get screened!

The authors state¹ that “in 2014, an estimated 172,258 men in the United States were diagnosed with prostate cancer, but only 28,343 men died of it.” Nevertheless, prostate cancer remains the second most common cause of cancer deaths in American men, after lung cancer.⁴ In addition to the reduction in prostate cancer-specific mortality with screening, patients should consider the reduction in morbidity from painful bone metastases and pathologic fractures, which are common in advanced prostate cancer.

A false-positive elevated PSA can be caused by reversible benign conditions, such as prostate infection or trauma, which can resolve over time, returning the PSA to its baseline level. Studies have demonstrated that simply repeating the PSA test a few weeks later will significantly reduce the number of false-positive PSA screening tests.⁵

Also, it is not optimal to screen for prostate cancer using a single PSA measurement. This patient’s PSA of 5.1 ng/mL cannot distinguish between chronic benign prostatic hyperplasia and a fast-growing but still curable malignancy. If the patient’s PSA had been tested annually and was known to be stable at its current level, a benign or indolent condition would be most likely, allowing for the possibility of continuing noninvasive observation. If his PSA was 1.1 ng/mL a year ago, and his PSA remains elevated when retested in a few weeks, the likelihood of malignancy would increase, increasing the yield of biopsy.

Lastly, consider false-negatives. A man with a PSA of 2.0 ng/mL would not have undergone biopsy in any of the trials, but if he had a history of several consecutive annual PSA levels less than 1.0 ng/mL, the doubling of his PSA during an interval less than or equal to 1 year could signal an early aggressive prostate cancer. Increases in PSA velocity can reveal the rapid proliferation of malignant prostate cells before the tumor is large enough to cross a static threshold PSA. We have zero data indicating how much benefit can be derived from the use of PSA velocity in this fashion. However, clinicians who carefully track serial PSA changes in each patient have anecdotes of success in early detection and cure of aggressive prostate cancers that would not have been detected by the trial protocols using fixed PSA thresholds. Until such trials are done, we can only tell patients that the ability to compute PSA velocity may be another source of benefit of annual screening of PSA.

To the Editor: In their article on men’s health,¹Chaitoff and colleagues present the scenario of a 60-year-old patient, with no other history given, whose recent screening prostate-specific antigen (PSA) level was 5.1 ng/mL, and who asks his doctor:

1. Should I have agreed to the screening?
2. How effective is the screening?
3. What are the next steps?

These questions are consistent with the patient having read the latest US Preventive Services Task Force (USPSTF) report on PSA screening, which states: “Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results…”²

I would tell the patient that he can expect greater benefit from PSA screening than reported by the USPSTF simply by adhering to the screening protocol. Intention-to-treat analysis applied to the trial results diminished the apparent benefits of PSA screening by counting fatal prostate cancers experienced by nonadherent study participants as screening failures.³ In other words, screening works better in those who actually get screened!

The authors state¹ that “in 2014, an estimated 172,258 men in the United States were diagnosed with prostate cancer, but only 28,343 men died of it.” Nevertheless, prostate cancer remains the second most common cause of cancer deaths in American men, after lung cancer.⁴ In addition to the reduction in prostate cancer-specific mortality with screening, patients should consider the reduction in morbidity from painful bone metastases and pathologic fractures, which are common in advanced prostate cancer.

A false-positive elevated PSA can be caused by reversible benign conditions, such as prostate infection or trauma, which can resolve over time, returning the PSA to its baseline level. Studies have demonstrated that simply repeating the PSA test a few weeks later will significantly reduce the number of false-positive PSA screening tests.⁵

Also, it is not optimal to screen for prostate cancer using a single PSA measurement. This patient’s PSA of 5.1 ng/mL cannot distinguish between chronic benign prostatic hyperplasia and a fast-growing but still curable malignancy. If the patient’s PSA had been tested annually and was known to be stable at its current level, a benign or indolent condition would be most likely, allowing for the possibility of continuing noninvasive observation. If his PSA was 1.1 ng/mL a year ago, and his PSA remains elevated when retested in a few weeks, the likelihood of malignancy would increase, increasing the yield of biopsy.

Lastly, consider false-negatives. A man with a PSA of 2.0 ng/mL would not have undergone biopsy in any of the trials, but if he had a history of several consecutive annual PSA levels less than 1.0 ng/mL, the doubling of his PSA during an interval less than or equal to 1 year could signal an early aggressive prostate cancer. Increases in PSA velocity can reveal the rapid proliferation of malignant prostate cells before the tumor is large enough to cross a static threshold PSA. We have zero data indicating how much benefit can be derived from the use of PSA velocity in this fashion. However, clinicians who carefully track serial PSA changes in each patient have anecdotes of success in early detection and cure of aggressive prostate cancers that would not have been detected by the trial protocols using fixed PSA thresholds. Until such trials are done, we can only tell patients that the ability to compute PSA velocity may be another source of benefit of annual screening of PSA.

To the Editor: In their article on men’s health,¹Chaitoff and colleagues present the scenario of a 60-year-old patient, with no other history given, whose recent screening prostate-specific antigen (PSA) level was 5.1 ng/mL, and who asks his doctor:

1. Should I have agreed to the screening?
2. How effective is the screening?
3. What are the next steps?

These questions are consistent with the patient having read the latest US Preventive Services Task Force (USPSTF) report on PSA screening, which states: “Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results…”²

I would tell the patient that he can expect greater benefit from PSA screening than reported by the USPSTF simply by adhering to the screening protocol. Intention-to-treat analysis applied to the trial results diminished the apparent benefits of PSA screening by counting fatal prostate cancers experienced by nonadherent study participants as screening failures.³ In other words, screening works better in those who actually get screened!

The authors state¹ that “in 2014, an estimated 172,258 men in the United States were diagnosed with prostate cancer, but only 28,343 men died of it.” Nevertheless, prostate cancer remains the second most common cause of cancer deaths in American men, after lung cancer.⁴ In addition to the reduction in prostate cancer-specific mortality with screening, patients should consider the reduction in morbidity from painful bone metastases and pathologic fractures, which are common in advanced prostate cancer.

A false-positive elevated PSA can be caused by reversible benign conditions, such as prostate infection or trauma, which can resolve over time, returning the PSA to its baseline level. Studies have demonstrated that simply repeating the PSA test a few weeks later will significantly reduce the number of false-positive PSA screening tests.⁵

Also, it is not optimal to screen for prostate cancer using a single PSA measurement. This patient’s PSA of 5.1 ng/mL cannot distinguish between chronic benign prostatic hyperplasia and a fast-growing but still curable malignancy. If the patient’s PSA had been tested annually and was known to be stable at its current level, a benign or indolent condition would be most likely, allowing for the possibility of continuing noninvasive observation. If his PSA was 1.1 ng/mL a year ago, and his PSA remains elevated when retested in a few weeks, the likelihood of malignancy would increase, increasing the yield of biopsy.

Lastly, consider false-negatives. A man with a PSA of 2.0 ng/mL would not have undergone biopsy in any of the trials, but if he had a history of several consecutive annual PSA levels less than 1.0 ng/mL, the doubling of his PSA during an interval less than or equal to 1 year could signal an early aggressive prostate cancer. Increases in PSA velocity can reveal the rapid proliferation of malignant prostate cells before the tumor is large enough to cross a static threshold PSA. We have zero data indicating how much benefit can be derived from the use of PSA velocity in this fashion. However, clinicians who carefully track serial PSA changes in each patient have anecdotes of success in early detection and cure of aggressive prostate cancers that would not have been detected by the trial protocols using fixed PSA thresholds. Until such trials are done, we can only tell patients that the ability to compute PSA velocity may be another source of benefit of annual screening of PSA.