OBG Management

In this Update, I report on the latest US Preventive Services Task Force (USPSTF) cervical cancer screening recommendations. In addition, I describe the results of 2 studies, a large prospective multicenter study of the accuracy of sentinel lymph node (SLN) biopsy in endometrial cancer, and a proof-of-concept review of use of checkpoint blockade to increase immune response and of its possible role in endometrial cancer.

hrHPV testing used alone as primary screening for cervical cancer: USPSTF recommendations

US Preventive Services Task Force. Draft recommendation statement: cervical cancer: screening. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Published October 2017. Accessed February 5, 2018.

‌

Despite our rapid advances in understanding the molecular underpinnings of cancer, gynecologic malignancies are still a major cause of morbidity and mortality among women. Cervical cancer stands as an example of how a cancer screening test can be implemented to reduce mortality. In this section, I report on the USPSTF cervical cancer screening recommendations, which were updated in October 2017.

Even with the widespread implementation of screening programs for cervical cancer in the United States, 13,240 women will be diagnosed with the disease in 2018, and 4,170 will die from cervical cancer.¹ Most often, cervical cancer occurs in women who have not been adequately screened. It is now recognized that the human papillomavirus (HPV) is the cause of cervical cancer.²

While cervical cytology has long been used as a screening test for cervical cancer, testing for high-risk HPV subtypes (hrHPV testing) also has been used as a screening modality. Traditionally, hrHPV testing is used in combination with cervical cytology, so called cotesting. There is convincing evidence that cervical cytology, as well as strategies that use hrHPV testing, can detect high-grade cervical precancers and cancers and thereby reduce mortality. However, cervical cancer screening is also associated with frequent follow-ups, invasive procedures performed to assess abnormal results, psychological distress, and adverse pregnancy outcomes of treatment for precancerous lesions.

The USPSTF based its new cervical cancer screening recommendations on clinical trial data and decision modeling of various screening strategies, and weighed the benefits and harms of each strategy.

Recommendations from the USPSTF

hrHPV screening for cervical cancer.  TheUSPSTF recommends screening with cervical cytology every 3 years for women 21 to 29 years of age. For women 30 to 65 years of age, screening with cytology every 3 years, or hrHPV testing alone used every 5 years, is recommended.

Data from large randomized trials suggest cytologic screening is slightly less sensitive than hrHPV testing in detecting high-grade (grade 2 or 3) cervical intraepithelial neoplasia (CIN). However, hrHPV testing results in more follow-up tests and colposcopies. In a decision model, the USPSTF found that cotesting increased the number of follow-up tests but did not increase detection of grade 3 CIN or invasive cancer. This is the first clinical guideline to recommend hrHPV testing used alone for screening. The American College of Obstetricians and Gynecologists (ACOG) continues to recommend cotesting (cytology in combination with hrHPV) as a primary screening modality in this population.³

Exceptions. According to the USPSTF, 3 populations should not be screened: women over 65 years of age with adequate prior screening who are not otherwise at high risk for cervical cancer; women under  21 years of age; and women who have had a hysterectomy and do not have a history of grade 2 or 3 CIN or cancer.

Summary. The USPSTF recommendations are intended for the general population and are not applicable to women with a history of high-grade CIN or cervical cancer, women with in utero exposure to diethylstilbestrol, and women who are immunocompromised. The remaining USPSTF recommendations are largely in line with guidelines published by ACOG and other groups.^3,4

Read about SLN biopsy to stage endometrial cancer

SLN biopsy for staging endometrial cancer

Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384-392.

‌

Surgery is the cornerstone of treatment for most gynecologic cancers. The widespread use of minimally invasive surgical techniques and the introduction of less radical procedures for gynecologic cancers have helped reduce surgical morbidity.

For endometrial cancer, the role of lymphadenectomy is controversial. Data from prospective trials of this procedure suggest an association with increased morbidity and long-term sequelae, such as lymphedema, and no association with improved survival.^5,6

SLN biopsy is an important advance and a potential alternative nodal evaluation method that may be associated with decreased morbidity. In this more limited assessment technique, the first nodal drainage basins of a tumor are identified and removed for pathologic evaluation.

Accuracy of SLN biopsy in endometrial cancer was the subject of Rossi and colleagues' recent large prospective multicenter study, the Fluorescence Imaging for Robotic Endometrial Sentinel lymph node biopsy (FIRES) trial.

Details of the study

Rossi and colleagues conducted the FIRES trial to estimate the sensitivity of SLN biopsy in detecting nodal metastases in women with stage I endometrial cancer. Patients (N = 385) from 10 US sites were enrolled in the study. SLN evaluation was performed after cervical injection of indocyanine green followed by robotic-assisted hysterectomy. After identification of the SLN, participants underwent pelvic lymphadenectomy. Performance of para-aortic lymphadenectomy was optional.

Mapping of the SLN was feasible in 86% of patients, including bilateral mapping in 52%. Twelve percent of the participants had nodal metastases. SLN biopsy had a sensitivity of 97% in women who had identification of the SLNs. Similarly, the negative predictive value was high, 99.6%. The procedure was associated with acceptable short-term toxicity with adverse events in 9% of study participants. Common complications included neurologic complications, respiratory distress, nausea and vomiting, and, in 3 patients, bowel injury.

Accurate detection of nodal metastases. Results of the study suggest SLN biopsy is accurate in detecting nodal metastases in women with endometrial cancer. Although long-term toxicity was not examined, other work suggests the lymphedema rates associated with SLN biopsy may be lower than those of lymphadenectomy. While the study described impressive performance characteristics, there remain technical challenges. Even among skilled surgeons trained for the protocol, there was no nodal mapping in nearly half of the women with endometrial cancer. Women without node mapping require full lymphadenectomy thus negating the possible benefits of the procedure.

Read about immunotherapy for gynecologic cancers

Immunotherapy for gynecologic cancers

Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413.

‌

In oncology, precision medicine is rapidly becoming a standard treatment approach. Therapies are being used to target specific genetic alterations in tumors. In cancer immunotherapy, the immune system is being used to facilitate clearance of cancer cells.

The most common mechanism of action of clinically used immunotherapeutic agents is blockade of programmed cell death protein 1 (PD-1), a lymphocyte receptor that prevents the immune system from targeting the body's own cells.⁷ Cancers that have mutations in the DNA mismatch repair (MMR) proteins display microsatellite instability (MSI) and produce high levels of abnormal proteins.⁸ These abnormal proteins serve as tumor antigens that can be targeted by the body's normal immune system. 

In May 2017, the US Food and Drug Administration (FDA) granted accelerated approval of the PD-1 blocking antibody pembrolizumab for the treatment of unresectable or metastatic MSI-high (MSI-H) or MMR-deficient solid tumors.9 The approval was based on data from 149 patients treated in 5 studies that demonstrated a response rate of 39.6%, including responses that lasted at least 6 months in 78% of participants. This was the first ever cancer drug that received FDA approval based on a tumor's biomarker profile without regard to the site of origin. I describe the results of a study by Le and colleagues that examines the possible role of immunotherapy in a variety of solid tumors in this section.

Details of the study

This study examined the clinical efficacy of PD-1 blockade in 86 patients with advanced, MMR-deficient tumors from 12 different sites. Endometrial cancer was the second most frequent primary tumor site in 17% of patients. Within the cohort, the overall objective response rate was 53%, which included 21% of patients with complete radiographic response (no imaging evidence of cancer). Disease control, either complete or partial response or stable disease, was achieved in 77% of patients. After a median follow-up of 12.5 months, neither the median progression-free survival (PFS) nor median overall survival had been reached. The authors estimated that 2-year overall survival was 64%, substantially higher than expected for patients with advanced solid tumors.

Le and colleagues also performed several in vivo laboratory experiments to explore the mechanisms by which patients responded. In addition, they used sequencing to determine the prevalence of MMR deficiency in 12,019 cancer samples that included 32 distinct tumor types (FIGURE). Endometrial cancer had the highest frequency of MMR deficiency (17%). Four percent of cervical cancers and less than 2% of ovarian cancers were MMR-deficient.

The promise of immunotherapy for endometrial cancer. This study's data and other emerging data have important implications for women with gynecologic cancer, particularly endometrial cancer. First, given the frequency of MMR mutations among women with endometrial cancer, MMR testing should be strongly considered for these patients. Many institutions have protocols for reflex testing with immunohistochemistry for women with endometrial cancer. For women with positive test results, germline sequencing can be performed to determine if they have an inherited MMR deficiency, Lynch syndrome. Presence of an MMR deficiency is an important factor in cancer screening and potential treatment.

Second, the impressive results of PD-1 blockade in patients with MMR-deficient tumors suggest that this treatment strategy may be important for women with recurrent or metastatic endometrial cancer. The ideal timing of immunotherapy for women with endometrial cancer is an area of active ongoing study.

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.

In this Update, I report on the latest US Preventive Services Task Force (USPSTF) cervical cancer screening recommendations. In addition, I describe the results of 2 studies, a large prospective multicenter study of the accuracy of sentinel lymph node (SLN) biopsy in endometrial cancer, and a proof-of-concept review of use of checkpoint blockade to increase immune response and of its possible role in endometrial cancer.

hrHPV testing used alone as primary screening for cervical cancer: USPSTF recommendations

US Preventive Services Task Force. Draft recommendation statement: cervical cancer: screening. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Published October 2017. Accessed February 5, 2018.

‌

Despite our rapid advances in understanding the molecular underpinnings of cancer, gynecologic malignancies are still a major cause of morbidity and mortality among women. Cervical cancer stands as an example of how a cancer screening test can be implemented to reduce mortality. In this section, I report on the USPSTF cervical cancer screening recommendations, which were updated in October 2017.

Even with the widespread implementation of screening programs for cervical cancer in the United States, 13,240 women will be diagnosed with the disease in 2018, and 4,170 will die from cervical cancer.¹ Most often, cervical cancer occurs in women who have not been adequately screened. It is now recognized that the human papillomavirus (HPV) is the cause of cervical cancer.²

While cervical cytology has long been used as a screening test for cervical cancer, testing for high-risk HPV subtypes (hrHPV testing) also has been used as a screening modality. Traditionally, hrHPV testing is used in combination with cervical cytology, so called cotesting. There is convincing evidence that cervical cytology, as well as strategies that use hrHPV testing, can detect high-grade cervical precancers and cancers and thereby reduce mortality. However, cervical cancer screening is also associated with frequent follow-ups, invasive procedures performed to assess abnormal results, psychological distress, and adverse pregnancy outcomes of treatment for precancerous lesions.

The USPSTF based its new cervical cancer screening recommendations on clinical trial data and decision modeling of various screening strategies, and weighed the benefits and harms of each strategy.

Recommendations from the USPSTF

hrHPV screening for cervical cancer.  TheUSPSTF recommends screening with cervical cytology every 3 years for women 21 to 29 years of age. For women 30 to 65 years of age, screening with cytology every 3 years, or hrHPV testing alone used every 5 years, is recommended.

Data from large randomized trials suggest cytologic screening is slightly less sensitive than hrHPV testing in detecting high-grade (grade 2 or 3) cervical intraepithelial neoplasia (CIN). However, hrHPV testing results in more follow-up tests and colposcopies. In a decision model, the USPSTF found that cotesting increased the number of follow-up tests but did not increase detection of grade 3 CIN or invasive cancer. This is the first clinical guideline to recommend hrHPV testing used alone for screening. The American College of Obstetricians and Gynecologists (ACOG) continues to recommend cotesting (cytology in combination with hrHPV) as a primary screening modality in this population.³

Exceptions. According to the USPSTF, 3 populations should not be screened: women over 65 years of age with adequate prior screening who are not otherwise at high risk for cervical cancer; women under  21 years of age; and women who have had a hysterectomy and do not have a history of grade 2 or 3 CIN or cancer.

Summary. The USPSTF recommendations are intended for the general population and are not applicable to women with a history of high-grade CIN or cervical cancer, women with in utero exposure to diethylstilbestrol, and women who are immunocompromised. The remaining USPSTF recommendations are largely in line with guidelines published by ACOG and other groups.^3,4

Read about SLN biopsy to stage endometrial cancer

SLN biopsy for staging endometrial cancer

Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384-392.

‌

Surgery is the cornerstone of treatment for most gynecologic cancers. The widespread use of minimally invasive surgical techniques and the introduction of less radical procedures for gynecologic cancers have helped reduce surgical morbidity.

For endometrial cancer, the role of lymphadenectomy is controversial. Data from prospective trials of this procedure suggest an association with increased morbidity and long-term sequelae, such as lymphedema, and no association with improved survival.^5,6

SLN biopsy is an important advance and a potential alternative nodal evaluation method that may be associated with decreased morbidity. In this more limited assessment technique, the first nodal drainage basins of a tumor are identified and removed for pathologic evaluation.

Accuracy of SLN biopsy in endometrial cancer was the subject of Rossi and colleagues' recent large prospective multicenter study, the Fluorescence Imaging for Robotic Endometrial Sentinel lymph node biopsy (FIRES) trial.

Details of the study

Rossi and colleagues conducted the FIRES trial to estimate the sensitivity of SLN biopsy in detecting nodal metastases in women with stage I endometrial cancer. Patients (N = 385) from 10 US sites were enrolled in the study. SLN evaluation was performed after cervical injection of indocyanine green followed by robotic-assisted hysterectomy. After identification of the SLN, participants underwent pelvic lymphadenectomy. Performance of para-aortic lymphadenectomy was optional.

Mapping of the SLN was feasible in 86% of patients, including bilateral mapping in 52%. Twelve percent of the participants had nodal metastases. SLN biopsy had a sensitivity of 97% in women who had identification of the SLNs. Similarly, the negative predictive value was high, 99.6%. The procedure was associated with acceptable short-term toxicity with adverse events in 9% of study participants. Common complications included neurologic complications, respiratory distress, nausea and vomiting, and, in 3 patients, bowel injury.

Accurate detection of nodal metastases. Results of the study suggest SLN biopsy is accurate in detecting nodal metastases in women with endometrial cancer. Although long-term toxicity was not examined, other work suggests the lymphedema rates associated with SLN biopsy may be lower than those of lymphadenectomy. While the study described impressive performance characteristics, there remain technical challenges. Even among skilled surgeons trained for the protocol, there was no nodal mapping in nearly half of the women with endometrial cancer. Women without node mapping require full lymphadenectomy thus negating the possible benefits of the procedure.

Read about immunotherapy for gynecologic cancers

Immunotherapy for gynecologic cancers

Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413.

‌

In oncology, precision medicine is rapidly becoming a standard treatment approach. Therapies are being used to target specific genetic alterations in tumors. In cancer immunotherapy, the immune system is being used to facilitate clearance of cancer cells.

The most common mechanism of action of clinically used immunotherapeutic agents is blockade of programmed cell death protein 1 (PD-1), a lymphocyte receptor that prevents the immune system from targeting the body's own cells.⁷ Cancers that have mutations in the DNA mismatch repair (MMR) proteins display microsatellite instability (MSI) and produce high levels of abnormal proteins.⁸ These abnormal proteins serve as tumor antigens that can be targeted by the body's normal immune system. 

In May 2017, the US Food and Drug Administration (FDA) granted accelerated approval of the PD-1 blocking antibody pembrolizumab for the treatment of unresectable or metastatic MSI-high (MSI-H) or MMR-deficient solid tumors.9 The approval was based on data from 149 patients treated in 5 studies that demonstrated a response rate of 39.6%, including responses that lasted at least 6 months in 78% of participants. This was the first ever cancer drug that received FDA approval based on a tumor's biomarker profile without regard to the site of origin. I describe the results of a study by Le and colleagues that examines the possible role of immunotherapy in a variety of solid tumors in this section.

Details of the study

This study examined the clinical efficacy of PD-1 blockade in 86 patients with advanced, MMR-deficient tumors from 12 different sites. Endometrial cancer was the second most frequent primary tumor site in 17% of patients. Within the cohort, the overall objective response rate was 53%, which included 21% of patients with complete radiographic response (no imaging evidence of cancer). Disease control, either complete or partial response or stable disease, was achieved in 77% of patients. After a median follow-up of 12.5 months, neither the median progression-free survival (PFS) nor median overall survival had been reached. The authors estimated that 2-year overall survival was 64%, substantially higher than expected for patients with advanced solid tumors.

Le and colleagues also performed several in vivo laboratory experiments to explore the mechanisms by which patients responded. In addition, they used sequencing to determine the prevalence of MMR deficiency in 12,019 cancer samples that included 32 distinct tumor types (FIGURE). Endometrial cancer had the highest frequency of MMR deficiency (17%). Four percent of cervical cancers and less than 2% of ovarian cancers were MMR-deficient.

The promise of immunotherapy for endometrial cancer. This study's data and other emerging data have important implications for women with gynecologic cancer, particularly endometrial cancer. First, given the frequency of MMR mutations among women with endometrial cancer, MMR testing should be strongly considered for these patients. Many institutions have protocols for reflex testing with immunohistochemistry for women with endometrial cancer. For women with positive test results, germline sequencing can be performed to determine if they have an inherited MMR deficiency, Lynch syndrome. Presence of an MMR deficiency is an important factor in cancer screening and potential treatment.

Second, the impressive results of PD-1 blockade in patients with MMR-deficient tumors suggest that this treatment strategy may be important for women with recurrent or metastatic endometrial cancer. The ideal timing of immunotherapy for women with endometrial cancer is an area of active ongoing study.

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.

In this Update, I report on the latest US Preventive Services Task Force (USPSTF) cervical cancer screening recommendations. In addition, I describe the results of 2 studies, a large prospective multicenter study of the accuracy of sentinel lymph node (SLN) biopsy in endometrial cancer, and a proof-of-concept review of use of checkpoint blockade to increase immune response and of its possible role in endometrial cancer.

hrHPV testing used alone as primary screening for cervical cancer: USPSTF recommendations

US Preventive Services Task Force. Draft recommendation statement: cervical cancer: screening. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Published October 2017. Accessed February 5, 2018.

‌

Despite our rapid advances in understanding the molecular underpinnings of cancer, gynecologic malignancies are still a major cause of morbidity and mortality among women. Cervical cancer stands as an example of how a cancer screening test can be implemented to reduce mortality. In this section, I report on the USPSTF cervical cancer screening recommendations, which were updated in October 2017.

Even with the widespread implementation of screening programs for cervical cancer in the United States, 13,240 women will be diagnosed with the disease in 2018, and 4,170 will die from cervical cancer.¹ Most often, cervical cancer occurs in women who have not been adequately screened. It is now recognized that the human papillomavirus (HPV) is the cause of cervical cancer.²

While cervical cytology has long been used as a screening test for cervical cancer, testing for high-risk HPV subtypes (hrHPV testing) also has been used as a screening modality. Traditionally, hrHPV testing is used in combination with cervical cytology, so called cotesting. There is convincing evidence that cervical cytology, as well as strategies that use hrHPV testing, can detect high-grade cervical precancers and cancers and thereby reduce mortality. However, cervical cancer screening is also associated with frequent follow-ups, invasive procedures performed to assess abnormal results, psychological distress, and adverse pregnancy outcomes of treatment for precancerous lesions.

The USPSTF based its new cervical cancer screening recommendations on clinical trial data and decision modeling of various screening strategies, and weighed the benefits and harms of each strategy.

Recommendations from the USPSTF

hrHPV screening for cervical cancer.  TheUSPSTF recommends screening with cervical cytology every 3 years for women 21 to 29 years of age. For women 30 to 65 years of age, screening with cytology every 3 years, or hrHPV testing alone used every 5 years, is recommended.

Data from large randomized trials suggest cytologic screening is slightly less sensitive than hrHPV testing in detecting high-grade (grade 2 or 3) cervical intraepithelial neoplasia (CIN). However, hrHPV testing results in more follow-up tests and colposcopies. In a decision model, the USPSTF found that cotesting increased the number of follow-up tests but did not increase detection of grade 3 CIN or invasive cancer. This is the first clinical guideline to recommend hrHPV testing used alone for screening. The American College of Obstetricians and Gynecologists (ACOG) continues to recommend cotesting (cytology in combination with hrHPV) as a primary screening modality in this population.³

Exceptions. According to the USPSTF, 3 populations should not be screened: women over 65 years of age with adequate prior screening who are not otherwise at high risk for cervical cancer; women under  21 years of age; and women who have had a hysterectomy and do not have a history of grade 2 or 3 CIN or cancer.

Summary. The USPSTF recommendations are intended for the general population and are not applicable to women with a history of high-grade CIN or cervical cancer, women with in utero exposure to diethylstilbestrol, and women who are immunocompromised. The remaining USPSTF recommendations are largely in line with guidelines published by ACOG and other groups.^3,4

Read about SLN biopsy to stage endometrial cancer

SLN biopsy for staging endometrial cancer

Rossi EC, Kowalski LD, Scalici J, et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384-392.

‌

Surgery is the cornerstone of treatment for most gynecologic cancers. The widespread use of minimally invasive surgical techniques and the introduction of less radical procedures for gynecologic cancers have helped reduce surgical morbidity.

For endometrial cancer, the role of lymphadenectomy is controversial. Data from prospective trials of this procedure suggest an association with increased morbidity and long-term sequelae, such as lymphedema, and no association with improved survival.^5,6

SLN biopsy is an important advance and a potential alternative nodal evaluation method that may be associated with decreased morbidity. In this more limited assessment technique, the first nodal drainage basins of a tumor are identified and removed for pathologic evaluation.

Accuracy of SLN biopsy in endometrial cancer was the subject of Rossi and colleagues' recent large prospective multicenter study, the Fluorescence Imaging for Robotic Endometrial Sentinel lymph node biopsy (FIRES) trial.

Details of the study

Rossi and colleagues conducted the FIRES trial to estimate the sensitivity of SLN biopsy in detecting nodal metastases in women with stage I endometrial cancer. Patients (N = 385) from 10 US sites were enrolled in the study. SLN evaluation was performed after cervical injection of indocyanine green followed by robotic-assisted hysterectomy. After identification of the SLN, participants underwent pelvic lymphadenectomy. Performance of para-aortic lymphadenectomy was optional.

Mapping of the SLN was feasible in 86% of patients, including bilateral mapping in 52%. Twelve percent of the participants had nodal metastases. SLN biopsy had a sensitivity of 97% in women who had identification of the SLNs. Similarly, the negative predictive value was high, 99.6%. The procedure was associated with acceptable short-term toxicity with adverse events in 9% of study participants. Common complications included neurologic complications, respiratory distress, nausea and vomiting, and, in 3 patients, bowel injury.

Accurate detection of nodal metastases. Results of the study suggest SLN biopsy is accurate in detecting nodal metastases in women with endometrial cancer. Although long-term toxicity was not examined, other work suggests the lymphedema rates associated with SLN biopsy may be lower than those of lymphadenectomy. While the study described impressive performance characteristics, there remain technical challenges. Even among skilled surgeons trained for the protocol, there was no nodal mapping in nearly half of the women with endometrial cancer. Women without node mapping require full lymphadenectomy thus negating the possible benefits of the procedure.

Read about immunotherapy for gynecologic cancers

Immunotherapy for gynecologic cancers

Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413.

‌

In oncology, precision medicine is rapidly becoming a standard treatment approach. Therapies are being used to target specific genetic alterations in tumors. In cancer immunotherapy, the immune system is being used to facilitate clearance of cancer cells.

The most common mechanism of action of clinically used immunotherapeutic agents is blockade of programmed cell death protein 1 (PD-1), a lymphocyte receptor that prevents the immune system from targeting the body's own cells.⁷ Cancers that have mutations in the DNA mismatch repair (MMR) proteins display microsatellite instability (MSI) and produce high levels of abnormal proteins.⁸ These abnormal proteins serve as tumor antigens that can be targeted by the body's normal immune system. 

In May 2017, the US Food and Drug Administration (FDA) granted accelerated approval of the PD-1 blocking antibody pembrolizumab for the treatment of unresectable or metastatic MSI-high (MSI-H) or MMR-deficient solid tumors.9 The approval was based on data from 149 patients treated in 5 studies that demonstrated a response rate of 39.6%, including responses that lasted at least 6 months in 78% of participants. This was the first ever cancer drug that received FDA approval based on a tumor's biomarker profile without regard to the site of origin. I describe the results of a study by Le and colleagues that examines the possible role of immunotherapy in a variety of solid tumors in this section.

Details of the study

This study examined the clinical efficacy of PD-1 blockade in 86 patients with advanced, MMR-deficient tumors from 12 different sites. Endometrial cancer was the second most frequent primary tumor site in 17% of patients. Within the cohort, the overall objective response rate was 53%, which included 21% of patients with complete radiographic response (no imaging evidence of cancer). Disease control, either complete or partial response or stable disease, was achieved in 77% of patients. After a median follow-up of 12.5 months, neither the median progression-free survival (PFS) nor median overall survival had been reached. The authors estimated that 2-year overall survival was 64%, substantially higher than expected for patients with advanced solid tumors.

Le and colleagues also performed several in vivo laboratory experiments to explore the mechanisms by which patients responded. In addition, they used sequencing to determine the prevalence of MMR deficiency in 12,019 cancer samples that included 32 distinct tumor types (FIGURE). Endometrial cancer had the highest frequency of MMR deficiency (17%). Four percent of cervical cancers and less than 2% of ovarian cancers were MMR-deficient.

The promise of immunotherapy for endometrial cancer. This study's data and other emerging data have important implications for women with gynecologic cancer, particularly endometrial cancer. First, given the frequency of MMR mutations among women with endometrial cancer, MMR testing should be strongly considered for these patients. Many institutions have protocols for reflex testing with immunohistochemistry for women with endometrial cancer. For women with positive test results, germline sequencing can be performed to determine if they have an inherited MMR deficiency, Lynch syndrome. Presence of an MMR deficiency is an important factor in cancer screening and potential treatment.

Second, the impressive results of PD-1 blockade in patients with MMR-deficient tumors suggest that this treatment strategy may be important for women with recurrent or metastatic endometrial cancer. The ideal timing of immunotherapy for women with endometrial cancer is an area of active ongoing study.

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.

In its landmark publication, “Crossing the quality chasm: A new health system for the 21st century,” the Institute of Medicine (now the National Academy of Medicine) called for an emphasis on patient-centered care that it defined as “Providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.”¹ Studies suggest that the patient’s view of health care delivery determines outcome and satisfaction.² Therefore, we need to expend more effort to understand what patients need or want from their treatment or interaction with the health care system.

Measuring patient-reported outcomes (PROs) is an attempt to recognize and address patient concerns. Although currently PROs are focused primarily in the arena of clinical research, their use has the potential to transform daily clinical patient encounters and improve the cost and quality of health care.³

In this article, we provide a brief overview of PROs and describe how they can be used to improve individual patient care, clinical research, and health care quality. We also offer examples of how PROs can be used in specific women’s health conditions.

Illustration: Paul Zwolak for OBG Management

What exactly are PROs?

PROs are reports of the status of a patient’s health condition, health behavior, or experience with health care; they come directly from the patient, without anyone else (such as a clinician or caregiver) interpreting the patient’s response.⁴ PROs usually pertain to general health, quality of life, functional status, or preferences associated with health care or treatment.⁵ Usually PROs are elicited via a self-administered survey and provide the patient’s perspective on treatment benefits, side effects, change in symptoms, general perceptions of feelings or well-being, or satisfaction with care. Often they represent the outcomes that are most important to patients.⁶ The survey usually consists of several questions or items. It can be general or condition specific, and it may represent one or more health care dimensions.

The term patient-reported outcome measure (PROM) refers to the survey instrument used to collect PROs. Patient-reported experience measures (PREMs), such as satisfaction surveys, are considered a subset of PROMs.⁷

Standardized PROs developed out of clinical trials

The use of PROs evolved from clinical trials. The proliferation of PROs resulted in an inability to compare outcomes across trials or different conditions. This led to a need to standardize and possibly harmonize measures and to reach consensus about properties required for a “good” measure and requirements needed for “adequate” reporting. Many investigators and several national and international organizations have provided iterative guidance, including the US Food and Drug Administration (FDA), European Medicines Agency, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS), International Consortium for Health Outcomes Measurement (ICHOM), University of Oxford Patient Reported Outcomes Measurement Group, Cochrane Systematic Reviews, Consolidated Standards of Reporting Trials–Patient Reported Outcomes (CONSORT-PRO) extension (how to report PROs with the CONSORT checklist), and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).^4,5,8–18

In the United States, the RAND Medical Outcomes Study led to the development of the 12- and 36-item short form surveys, which are widely recognized and commonly used PROMs for health-related quality of life.¹⁹ The study generated multiple additional survey instruments that evaluate other domains and dimensions of health. These surveys have been translated into numerous languages, and the RAND website lists over 100 publications.¹⁹

In 2002, the NIH sponsored PROMIS, a cooperative program designed to develop, validate, and standardize item banks to measure PROs that were relevant across multiple, common medical conditions. Based on literature review, feedback from both healthy and sick patients, and clinical expert opinion, the PROMIS investigators developed a consensus-based framework for self-reported health that included the following domains: pain, fatigue, emotional distress, physical functioning, and social role participation; these domains were evaluated on paper or with computer-assisted technology.^11–14 PROMIS is now a web-based resource with approximately 70 domains pertinent to children and adults in the general population and in those with chronic disease. Measures have been translated into more than 40 languages, and PROMIS-related work has resulted in more than 400 publications.¹⁴

In 2006, the FDA issued a draft document regarding the PRO standards that should be included in clinical trials for consideration of drug and device applications (TABLE 1). These recommendations, updated in 2009, were largely drawn from work published by PROMIS and University of Oxford investigators.^4,14,16

ICHOM specified 2 goals: 1) the core sets should be used in routine clinical practice, and 2) the core sets should be used as end points in clinical studies.¹⁵

As of May 2015, 12 standard sets of outcomes have been developed, representing 35% of the global burden of disease. ICHOM currently is creating networks of hospitals around the world to begin measuring, benchmarking, and performing outcome comparisons that can ultimately be used to inform global health system learning and clinical care improvement.¹⁵

Read about the evolving use of PROs

Use of PROs is evolving

Historically, PROMs have been used primarily in clinical trials to document the relative benefits of an intervention. With today’s focus on patient-centered care, however, there is a growing mandate to integrate PROMs into clinical care, quality improvement, and ultimately reimbursement. Recently, Basch and colleagues eloquently described the benefit of routine collection of PROs for cancer patients and the opportunity for improved care across the health system.²⁰

PROs can be applied on various levels. For example, if a patient reports a symptom (X), or a change in symptom X, the following options are possible:

• Clinician level: Symptom management with altered dose or change in medication. This is associated with improved self-efficacy for the patient, a shift toward goal-oriented care, improved communication with the provider, and improved patient satisfaction.
• Researcher level: PROs should be used as a primary end point, in addition to traditional outcomes (mortality, survival, physiologic markers), to allow for comparative effectiveness studies or patient-centered outcomes research studies that evaluate what matters most to patients relative to the specific health condition, intervention, and symptom management.
• Health system level: Quality assurance, quality improvement activities. How effective is the health system in the management of symptom X? Are all clinicians using the same medication or the same dose? Is there a best practice for managing symptom X?
• Population level: Provides evidence for other clinicians and patients to make decisions about what to expect with treatment for symptom X.

From a reimbursement level, clinicians and providers are paid based on performance—the more satisfied patients are about X, the higher the reimbursement. This has been pertinent particularly in high-volume orthopedic conditions in which anatomic correction of hip or knee joints has not consistently demonstrated improvement in quality of life as measured by the following PROs: perception of pain, mobility, physical functioning, social functioning, and emotional distress. Because of concerns about high volume, high cost, and inconsistent outcomes, the US Department of Health and Human Services has specified that 50% of Medicare and 90% of Medicaid reimbursements will be based on outcomes or value-based purchasing options.²¹

Studies have shown that it is possible to collect PRO data for cancer patients—despite age or severity of illness—and integrate it into clinical care delivery. These data can provide useful, actionable information, resulting in decreased emergency department visits, longer toleration of chemotherapy, and improved survival.²² Similar results have been demonstrated in other medical conditions, although challenges exist when transitioning from research settings to routine care. Challenges include privacy concerns, patient recruitment and tracking, encouraging patients to complete the PRO surveys (nonresponse leads to biased data), real and perceived administrative burden to staff, obtaining clinician buy in, and costs related to surveys and data analysis.²³

Read about the benefits of PROs to patients and clients

Using PROs in women’s health care: Benefits for patients and clinicians

According to a study by Frosch, patients want to know if a prescribed therapy actually improves outcomes, not whether it changes an isolated biomarker that does not translate into subjective improvement.²⁴ They want to know if the trade-off (adverse effects or higher cost) associated with a new drug or therapy is worth the improved mobility or time spent pain free.

Intuitively, all clinicians have similar opportunities for discussions with regard to the risks, benefits, and alternatives of medical treatment, surgical treatment, or expectant management. We routinely document this discussion daily. However, in this era of patient-centered care, when a patient asks, “What should I do, doctor?” we no longer can respond with a default recommendation. We must engage the patient and ask, “What do you want to do? What is most important to you?”

ObGyns are well suited to benefit from standardized efforts to collect PROs, as we frequently discuss with our patients trade-offs regarding treatment risks and benefits and their personal values and preferences. Examples include contraception options, hormone treatment for menopause, medication use during pregnancy, decisions at the limits of viability, preterm delivery for severe preeclampsia, induction/augmentation versus spontaneous labor, epidural versus physiologic labor, repeat cesarean versus vaginal birth after cesarean, and even elective primary cesarean versus vaginal birth.

Validated PROMs exist for benign gynecology, such as abnormal uterine bleeding, fibroids, polycystic ovary syndrome (PCOS), infertility, pelvic organ prolapse and/or urinary incontinence, and surgery for benign gynecology symptoms, as well as for cancer (breast, ovarian, cervical).^25–39

From the PCOS literature we can glean a poignant example of the importance of PROs. Martin and colleagues compared patient and clinician interviews regarding important PROs from the patient perspective.²⁹ Patients identified pain, cramping, heavy bleeding, and bloating as important, whereas clinicians did not consider these symptoms important to patients with PCOS. Clinicians thought “issues with menstruation,” characterized as irregular or no periods, were important, whereas patients were more concerned with heavy bleeding or bleeding of long duration. The authors concluded that concepts frequently expressed by patients and considered important from their perspective did not register with clinicians as being relevant and are not captured on current PRO instruments, emphasizing our knowledge gap and the need to pay attention to what patients want.²⁹

Surprisingly, although pregnancy and childbirth is the number one cause for hospital admissions, a highly preference-driven condition, and a leading cause of morbidity, mortality, and costs, there are few published PROs in the field. In a systematic review of more than 1,700 articles describing PROs published in English through 2014, Martin found that fewer than 1% included PROs specific to pregnancy and childbirth.⁴⁰

ICHOM has created a standard set of outcomes for pregnancy and childbirth based on consensus recommendations from physicians, measurement experts, and patients.⁴¹ The consortium describes 4 domains and 14 subdomains (TABLE 2) and provides suggestions for a validated PROM if known or where appropriate.

Similar domains and subdomains have been corroborated by our research team (the Maternal Quality Indicator [MQI] Work Group), the Childbirth Connection, and Gartner and colleagues.^42–44 The MQI Work Group recently conducted a national survey of what women want and what they think is important for their childbirth experience. We identified 19 domains, consistent with those of other investigators.⁴² Gartner and colleagues advocate for a composite outcome measure that combines the core domains into one preference-based utility measure that is weighted.⁴⁴ The rationale for this recommendation is that the levels of the domains might contribute differently to the overall birth experience. For example, communication might contribute more to an overall measure than pain management.⁴⁴ The development of a childbirth-specific survey to evaluate patient-reported outcomes and patient-reported experiences with care is needed if we are to provide value-based care in this arena.⁴⁵

Looking forward

PROs, PROMs, and PREMs are here to stay. They no longer are limited to clinical research, but increasingly will be incorporated into clinical care, providing us with opportunities to improve the quality of health care delivery, efficiency of patient/clinician interactions, and patients’ ratings of their health care experience.

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.

In its landmark publication, “Crossing the quality chasm: A new health system for the 21st century,” the Institute of Medicine (now the National Academy of Medicine) called for an emphasis on patient-centered care that it defined as “Providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.”¹ Studies suggest that the patient’s view of health care delivery determines outcome and satisfaction.² Therefore, we need to expend more effort to understand what patients need or want from their treatment or interaction with the health care system.

Measuring patient-reported outcomes (PROs) is an attempt to recognize and address patient concerns. Although currently PROs are focused primarily in the arena of clinical research, their use has the potential to transform daily clinical patient encounters and improve the cost and quality of health care.³

In this article, we provide a brief overview of PROs and describe how they can be used to improve individual patient care, clinical research, and health care quality. We also offer examples of how PROs can be used in specific women’s health conditions.

Illustration: Paul Zwolak for OBG Management

What exactly are PROs?

PROs are reports of the status of a patient’s health condition, health behavior, or experience with health care; they come directly from the patient, without anyone else (such as a clinician or caregiver) interpreting the patient’s response.⁴ PROs usually pertain to general health, quality of life, functional status, or preferences associated with health care or treatment.⁵ Usually PROs are elicited via a self-administered survey and provide the patient’s perspective on treatment benefits, side effects, change in symptoms, general perceptions of feelings or well-being, or satisfaction with care. Often they represent the outcomes that are most important to patients.⁶ The survey usually consists of several questions or items. It can be general or condition specific, and it may represent one or more health care dimensions.

The term patient-reported outcome measure (PROM) refers to the survey instrument used to collect PROs. Patient-reported experience measures (PREMs), such as satisfaction surveys, are considered a subset of PROMs.⁷

Standardized PROs developed out of clinical trials

The use of PROs evolved from clinical trials. The proliferation of PROs resulted in an inability to compare outcomes across trials or different conditions. This led to a need to standardize and possibly harmonize measures and to reach consensus about properties required for a “good” measure and requirements needed for “adequate” reporting. Many investigators and several national and international organizations have provided iterative guidance, including the US Food and Drug Administration (FDA), European Medicines Agency, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS), International Consortium for Health Outcomes Measurement (ICHOM), University of Oxford Patient Reported Outcomes Measurement Group, Cochrane Systematic Reviews, Consolidated Standards of Reporting Trials–Patient Reported Outcomes (CONSORT-PRO) extension (how to report PROs with the CONSORT checklist), and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).^4,5,8–18

In the United States, the RAND Medical Outcomes Study led to the development of the 12- and 36-item short form surveys, which are widely recognized and commonly used PROMs for health-related quality of life.¹⁹ The study generated multiple additional survey instruments that evaluate other domains and dimensions of health. These surveys have been translated into numerous languages, and the RAND website lists over 100 publications.¹⁹

In 2002, the NIH sponsored PROMIS, a cooperative program designed to develop, validate, and standardize item banks to measure PROs that were relevant across multiple, common medical conditions. Based on literature review, feedback from both healthy and sick patients, and clinical expert opinion, the PROMIS investigators developed a consensus-based framework for self-reported health that included the following domains: pain, fatigue, emotional distress, physical functioning, and social role participation; these domains were evaluated on paper or with computer-assisted technology.^11–14 PROMIS is now a web-based resource with approximately 70 domains pertinent to children and adults in the general population and in those with chronic disease. Measures have been translated into more than 40 languages, and PROMIS-related work has resulted in more than 400 publications.¹⁴

In 2006, the FDA issued a draft document regarding the PRO standards that should be included in clinical trials for consideration of drug and device applications (TABLE 1). These recommendations, updated in 2009, were largely drawn from work published by PROMIS and University of Oxford investigators.^4,14,16

ICHOM specified 2 goals: 1) the core sets should be used in routine clinical practice, and 2) the core sets should be used as end points in clinical studies.¹⁵

As of May 2015, 12 standard sets of outcomes have been developed, representing 35% of the global burden of disease. ICHOM currently is creating networks of hospitals around the world to begin measuring, benchmarking, and performing outcome comparisons that can ultimately be used to inform global health system learning and clinical care improvement.¹⁵

Read about the evolving use of PROs

Use of PROs is evolving

Historically, PROMs have been used primarily in clinical trials to document the relative benefits of an intervention. With today’s focus on patient-centered care, however, there is a growing mandate to integrate PROMs into clinical care, quality improvement, and ultimately reimbursement. Recently, Basch and colleagues eloquently described the benefit of routine collection of PROs for cancer patients and the opportunity for improved care across the health system.²⁰

PROs can be applied on various levels. For example, if a patient reports a symptom (X), or a change in symptom X, the following options are possible:

• Clinician level: Symptom management with altered dose or change in medication. This is associated with improved self-efficacy for the patient, a shift toward goal-oriented care, improved communication with the provider, and improved patient satisfaction.
• Researcher level: PROs should be used as a primary end point, in addition to traditional outcomes (mortality, survival, physiologic markers), to allow for comparative effectiveness studies or patient-centered outcomes research studies that evaluate what matters most to patients relative to the specific health condition, intervention, and symptom management.
• Health system level: Quality assurance, quality improvement activities. How effective is the health system in the management of symptom X? Are all clinicians using the same medication or the same dose? Is there a best practice for managing symptom X?
• Population level: Provides evidence for other clinicians and patients to make decisions about what to expect with treatment for symptom X.

From a reimbursement level, clinicians and providers are paid based on performance—the more satisfied patients are about X, the higher the reimbursement. This has been pertinent particularly in high-volume orthopedic conditions in which anatomic correction of hip or knee joints has not consistently demonstrated improvement in quality of life as measured by the following PROs: perception of pain, mobility, physical functioning, social functioning, and emotional distress. Because of concerns about high volume, high cost, and inconsistent outcomes, the US Department of Health and Human Services has specified that 50% of Medicare and 90% of Medicaid reimbursements will be based on outcomes or value-based purchasing options.²¹

Studies have shown that it is possible to collect PRO data for cancer patients—despite age or severity of illness—and integrate it into clinical care delivery. These data can provide useful, actionable information, resulting in decreased emergency department visits, longer toleration of chemotherapy, and improved survival.²² Similar results have been demonstrated in other medical conditions, although challenges exist when transitioning from research settings to routine care. Challenges include privacy concerns, patient recruitment and tracking, encouraging patients to complete the PRO surveys (nonresponse leads to biased data), real and perceived administrative burden to staff, obtaining clinician buy in, and costs related to surveys and data analysis.²³

Read about the benefits of PROs to patients and clients

Using PROs in women’s health care: Benefits for patients and clinicians

According to a study by Frosch, patients want to know if a prescribed therapy actually improves outcomes, not whether it changes an isolated biomarker that does not translate into subjective improvement.²⁴ They want to know if the trade-off (adverse effects or higher cost) associated with a new drug or therapy is worth the improved mobility or time spent pain free.

Intuitively, all clinicians have similar opportunities for discussions with regard to the risks, benefits, and alternatives of medical treatment, surgical treatment, or expectant management. We routinely document this discussion daily. However, in this era of patient-centered care, when a patient asks, “What should I do, doctor?” we no longer can respond with a default recommendation. We must engage the patient and ask, “What do you want to do? What is most important to you?”

ObGyns are well suited to benefit from standardized efforts to collect PROs, as we frequently discuss with our patients trade-offs regarding treatment risks and benefits and their personal values and preferences. Examples include contraception options, hormone treatment for menopause, medication use during pregnancy, decisions at the limits of viability, preterm delivery for severe preeclampsia, induction/augmentation versus spontaneous labor, epidural versus physiologic labor, repeat cesarean versus vaginal birth after cesarean, and even elective primary cesarean versus vaginal birth.

Validated PROMs exist for benign gynecology, such as abnormal uterine bleeding, fibroids, polycystic ovary syndrome (PCOS), infertility, pelvic organ prolapse and/or urinary incontinence, and surgery for benign gynecology symptoms, as well as for cancer (breast, ovarian, cervical).^25–39

From the PCOS literature we can glean a poignant example of the importance of PROs. Martin and colleagues compared patient and clinician interviews regarding important PROs from the patient perspective.²⁹ Patients identified pain, cramping, heavy bleeding, and bloating as important, whereas clinicians did not consider these symptoms important to patients with PCOS. Clinicians thought “issues with menstruation,” characterized as irregular or no periods, were important, whereas patients were more concerned with heavy bleeding or bleeding of long duration. The authors concluded that concepts frequently expressed by patients and considered important from their perspective did not register with clinicians as being relevant and are not captured on current PRO instruments, emphasizing our knowledge gap and the need to pay attention to what patients want.²⁹

Surprisingly, although pregnancy and childbirth is the number one cause for hospital admissions, a highly preference-driven condition, and a leading cause of morbidity, mortality, and costs, there are few published PROs in the field. In a systematic review of more than 1,700 articles describing PROs published in English through 2014, Martin found that fewer than 1% included PROs specific to pregnancy and childbirth.⁴⁰

ICHOM has created a standard set of outcomes for pregnancy and childbirth based on consensus recommendations from physicians, measurement experts, and patients.⁴¹ The consortium describes 4 domains and 14 subdomains (TABLE 2) and provides suggestions for a validated PROM if known or where appropriate.

Similar domains and subdomains have been corroborated by our research team (the Maternal Quality Indicator [MQI] Work Group), the Childbirth Connection, and Gartner and colleagues.^42–44 The MQI Work Group recently conducted a national survey of what women want and what they think is important for their childbirth experience. We identified 19 domains, consistent with those of other investigators.⁴² Gartner and colleagues advocate for a composite outcome measure that combines the core domains into one preference-based utility measure that is weighted.⁴⁴ The rationale for this recommendation is that the levels of the domains might contribute differently to the overall birth experience. For example, communication might contribute more to an overall measure than pain management.⁴⁴ The development of a childbirth-specific survey to evaluate patient-reported outcomes and patient-reported experiences with care is needed if we are to provide value-based care in this arena.⁴⁵

Looking forward

PROs, PROMs, and PREMs are here to stay. They no longer are limited to clinical research, but increasingly will be incorporated into clinical care, providing us with opportunities to improve the quality of health care delivery, efficiency of patient/clinician interactions, and patients’ ratings of their health care experience.

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.

In its landmark publication, “Crossing the quality chasm: A new health system for the 21st century,” the Institute of Medicine (now the National Academy of Medicine) called for an emphasis on patient-centered care that it defined as “Providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.”¹ Studies suggest that the patient’s view of health care delivery determines outcome and satisfaction.² Therefore, we need to expend more effort to understand what patients need or want from their treatment or interaction with the health care system.

Measuring patient-reported outcomes (PROs) is an attempt to recognize and address patient concerns. Although currently PROs are focused primarily in the arena of clinical research, their use has the potential to transform daily clinical patient encounters and improve the cost and quality of health care.³

In this article, we provide a brief overview of PROs and describe how they can be used to improve individual patient care, clinical research, and health care quality. We also offer examples of how PROs can be used in specific women’s health conditions.

Illustration: Paul Zwolak for OBG Management

What exactly are PROs?

PROs are reports of the status of a patient’s health condition, health behavior, or experience with health care; they come directly from the patient, without anyone else (such as a clinician or caregiver) interpreting the patient’s response.⁴ PROs usually pertain to general health, quality of life, functional status, or preferences associated with health care or treatment.⁵ Usually PROs are elicited via a self-administered survey and provide the patient’s perspective on treatment benefits, side effects, change in symptoms, general perceptions of feelings or well-being, or satisfaction with care. Often they represent the outcomes that are most important to patients.⁶ The survey usually consists of several questions or items. It can be general or condition specific, and it may represent one or more health care dimensions.

The term patient-reported outcome measure (PROM) refers to the survey instrument used to collect PROs. Patient-reported experience measures (PREMs), such as satisfaction surveys, are considered a subset of PROMs.⁷

Standardized PROs developed out of clinical trials

The use of PROs evolved from clinical trials. The proliferation of PROs resulted in an inability to compare outcomes across trials or different conditions. This led to a need to standardize and possibly harmonize measures and to reach consensus about properties required for a “good” measure and requirements needed for “adequate” reporting. Many investigators and several national and international organizations have provided iterative guidance, including the US Food and Drug Administration (FDA), European Medicines Agency, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS), International Consortium for Health Outcomes Measurement (ICHOM), University of Oxford Patient Reported Outcomes Measurement Group, Cochrane Systematic Reviews, Consolidated Standards of Reporting Trials–Patient Reported Outcomes (CONSORT-PRO) extension (how to report PROs with the CONSORT checklist), and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR).^4,5,8–18

In the United States, the RAND Medical Outcomes Study led to the development of the 12- and 36-item short form surveys, which are widely recognized and commonly used PROMs for health-related quality of life.¹⁹ The study generated multiple additional survey instruments that evaluate other domains and dimensions of health. These surveys have been translated into numerous languages, and the RAND website lists over 100 publications.¹⁹

In 2002, the NIH sponsored PROMIS, a cooperative program designed to develop, validate, and standardize item banks to measure PROs that were relevant across multiple, common medical conditions. Based on literature review, feedback from both healthy and sick patients, and clinical expert opinion, the PROMIS investigators developed a consensus-based framework for self-reported health that included the following domains: pain, fatigue, emotional distress, physical functioning, and social role participation; these domains were evaluated on paper or with computer-assisted technology.^11–14 PROMIS is now a web-based resource with approximately 70 domains pertinent to children and adults in the general population and in those with chronic disease. Measures have been translated into more than 40 languages, and PROMIS-related work has resulted in more than 400 publications.¹⁴

In 2006, the FDA issued a draft document regarding the PRO standards that should be included in clinical trials for consideration of drug and device applications (TABLE 1). These recommendations, updated in 2009, were largely drawn from work published by PROMIS and University of Oxford investigators.^4,14,16

ICHOM specified 2 goals: 1) the core sets should be used in routine clinical practice, and 2) the core sets should be used as end points in clinical studies.¹⁵

As of May 2015, 12 standard sets of outcomes have been developed, representing 35% of the global burden of disease. ICHOM currently is creating networks of hospitals around the world to begin measuring, benchmarking, and performing outcome comparisons that can ultimately be used to inform global health system learning and clinical care improvement.¹⁵

Read about the evolving use of PROs

Use of PROs is evolving

Historically, PROMs have been used primarily in clinical trials to document the relative benefits of an intervention. With today’s focus on patient-centered care, however, there is a growing mandate to integrate PROMs into clinical care, quality improvement, and ultimately reimbursement. Recently, Basch and colleagues eloquently described the benefit of routine collection of PROs for cancer patients and the opportunity for improved care across the health system.²⁰

PROs can be applied on various levels. For example, if a patient reports a symptom (X), or a change in symptom X, the following options are possible:

• Clinician level: Symptom management with altered dose or change in medication. This is associated with improved self-efficacy for the patient, a shift toward goal-oriented care, improved communication with the provider, and improved patient satisfaction.
• Researcher level: PROs should be used as a primary end point, in addition to traditional outcomes (mortality, survival, physiologic markers), to allow for comparative effectiveness studies or patient-centered outcomes research studies that evaluate what matters most to patients relative to the specific health condition, intervention, and symptom management.
• Health system level: Quality assurance, quality improvement activities. How effective is the health system in the management of symptom X? Are all clinicians using the same medication or the same dose? Is there a best practice for managing symptom X?
• Population level: Provides evidence for other clinicians and patients to make decisions about what to expect with treatment for symptom X.

From a reimbursement level, clinicians and providers are paid based on performance—the more satisfied patients are about X, the higher the reimbursement. This has been pertinent particularly in high-volume orthopedic conditions in which anatomic correction of hip or knee joints has not consistently demonstrated improvement in quality of life as measured by the following PROs: perception of pain, mobility, physical functioning, social functioning, and emotional distress. Because of concerns about high volume, high cost, and inconsistent outcomes, the US Department of Health and Human Services has specified that 50% of Medicare and 90% of Medicaid reimbursements will be based on outcomes or value-based purchasing options.²¹

Studies have shown that it is possible to collect PRO data for cancer patients—despite age or severity of illness—and integrate it into clinical care delivery. These data can provide useful, actionable information, resulting in decreased emergency department visits, longer toleration of chemotherapy, and improved survival.²² Similar results have been demonstrated in other medical conditions, although challenges exist when transitioning from research settings to routine care. Challenges include privacy concerns, patient recruitment and tracking, encouraging patients to complete the PRO surveys (nonresponse leads to biased data), real and perceived administrative burden to staff, obtaining clinician buy in, and costs related to surveys and data analysis.²³

Read about the benefits of PROs to patients and clients

Using PROs in women’s health care: Benefits for patients and clinicians

According to a study by Frosch, patients want to know if a prescribed therapy actually improves outcomes, not whether it changes an isolated biomarker that does not translate into subjective improvement.²⁴ They want to know if the trade-off (adverse effects or higher cost) associated with a new drug or therapy is worth the improved mobility or time spent pain free.

Intuitively, all clinicians have similar opportunities for discussions with regard to the risks, benefits, and alternatives of medical treatment, surgical treatment, or expectant management. We routinely document this discussion daily. However, in this era of patient-centered care, when a patient asks, “What should I do, doctor?” we no longer can respond with a default recommendation. We must engage the patient and ask, “What do you want to do? What is most important to you?”

ObGyns are well suited to benefit from standardized efforts to collect PROs, as we frequently discuss with our patients trade-offs regarding treatment risks and benefits and their personal values and preferences. Examples include contraception options, hormone treatment for menopause, medication use during pregnancy, decisions at the limits of viability, preterm delivery for severe preeclampsia, induction/augmentation versus spontaneous labor, epidural versus physiologic labor, repeat cesarean versus vaginal birth after cesarean, and even elective primary cesarean versus vaginal birth.

Validated PROMs exist for benign gynecology, such as abnormal uterine bleeding, fibroids, polycystic ovary syndrome (PCOS), infertility, pelvic organ prolapse and/or urinary incontinence, and surgery for benign gynecology symptoms, as well as for cancer (breast, ovarian, cervical).^25–39

From the PCOS literature we can glean a poignant example of the importance of PROs. Martin and colleagues compared patient and clinician interviews regarding important PROs from the patient perspective.²⁹ Patients identified pain, cramping, heavy bleeding, and bloating as important, whereas clinicians did not consider these symptoms important to patients with PCOS. Clinicians thought “issues with menstruation,” characterized as irregular or no periods, were important, whereas patients were more concerned with heavy bleeding or bleeding of long duration. The authors concluded that concepts frequently expressed by patients and considered important from their perspective did not register with clinicians as being relevant and are not captured on current PRO instruments, emphasizing our knowledge gap and the need to pay attention to what patients want.²⁹

Surprisingly, although pregnancy and childbirth is the number one cause for hospital admissions, a highly preference-driven condition, and a leading cause of morbidity, mortality, and costs, there are few published PROs in the field. In a systematic review of more than 1,700 articles describing PROs published in English through 2014, Martin found that fewer than 1% included PROs specific to pregnancy and childbirth.⁴⁰

ICHOM has created a standard set of outcomes for pregnancy and childbirth based on consensus recommendations from physicians, measurement experts, and patients.⁴¹ The consortium describes 4 domains and 14 subdomains (TABLE 2) and provides suggestions for a validated PROM if known or where appropriate.

Similar domains and subdomains have been corroborated by our research team (the Maternal Quality Indicator [MQI] Work Group), the Childbirth Connection, and Gartner and colleagues.^42–44 The MQI Work Group recently conducted a national survey of what women want and what they think is important for their childbirth experience. We identified 19 domains, consistent with those of other investigators.⁴² Gartner and colleagues advocate for a composite outcome measure that combines the core domains into one preference-based utility measure that is weighted.⁴⁴ The rationale for this recommendation is that the levels of the domains might contribute differently to the overall birth experience. For example, communication might contribute more to an overall measure than pain management.⁴⁴ The development of a childbirth-specific survey to evaluate patient-reported outcomes and patient-reported experiences with care is needed if we are to provide value-based care in this arena.⁴⁵

Looking forward

PROs, PROMs, and PREMs are here to stay. They no longer are limited to clinical research, but increasingly will be incorporated into clinical care, providing us with opportunities to improve the quality of health care delivery, efficiency of patient/clinician interactions, and patients’ ratings of their health care experience.

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.

EXPERT COMMENTARY

Lower urinary tract infection (UTI) is one of the most common medical complications of pregnancy. Approximately 5% to 10% of all pregnant women have asymptomatic bacteriuria, which usually antedates the pregnancy and is detected at the time of the first prenatal appointment. Another 2% to 3% develop acute cystitis during pregnancy. The dominant organisms that cause lower UTIs in pregnant women are Escherichia coli, Klebsiella pneumoniae, Proteus species, group B streptococci, enterococci, and Staphylococcus saprophyticus.

One goal of treating asymptomatic bacteriuria and acute cystitis is to prevent ascending infection (pyelonephritis), which can be associated with preterm delivery, sepsis, and adult respiratory distress syndrome. Another key goal is to use an antibiotic that eradicates the uropathogen without causing harm to either the mother or fetus.

In 2009, Crider and colleagues reported that 2 of the most commonly used antibiotics for UTIs, sulfonamides and nitrofurantoin, were associated with a disturbing spectrum of birth defects.¹ Following that report, in 2011 the American College of Obstetricians and Gynecologists (ACOG) published a committee opinion that recommended against the use of these 2 agents in the first trimester of pregnancy unless other antibiotics were unlikely to be effective.²

Details of the study

Centers for Disease Control and Prevention investigators recently conducted a study to assess the effect of these ACOG recommendations on clinical practice. Ailes and co-workers used the Truven Health MarketScan Commercial Database to examine antibiotic prescriptions filled by pregnant women with UTIs.

The database included 482,917 pregnancies in 2014 eligible for analysis. A total of 7.2% (n = 34,864) of pregnant women were treated as outpatients for a UTI within the 90-day interval before the last menstrual period or during the pregnancy. Among these women, the most commonly prescribed antibiotics during the first trimester were nitrofurantoin (34.7%), ciprofloxacin (10.5%), cephalexin (10.3%), and trimethoprim-sulfamethoxazole (7.6%).

The authors concluded that 43% of women used an antibiotic (nitrofurantoin or trimethoprim-sulfamethoxazole) in the first trimester that had potential teratogenicity, despite the precautionary statement articulated in the ACOG committee opinion.²

Antibiotic-associated effects

Of all the antibiotics that could be used to treat a lower UTI in pregnancy, nitrofurantoin probably has the greatest appeal. The drug is highly concentrated in the urine and is very active against all the common uropathogens except Proteus species. It is not absorbed significantly outside the lower urinary tract, and thus it does not alter the natural flora of the bowel or vagina (such alteration would predispose the patient to antibiotic-associated diarrhea or vulvovaginal candidiasis). Nitrofurantoin is inexpensive and usually is very well tolerated.

In the National Birth Defects Prevention Study by Crider and colleagues, nitrofurantoin was associated with anophthalmia or microphthalmos (adjusted odds ratio [AOR], 3.7; 95% confidence interval [CI], 1.1–12.2), hypoplastic left heart syndrome (AOR, 4.2; 95% CI, 1.9–9.1), atrial septal defects (AOR, 1.9; 95% CI, 1.1–3.4), and cleft lip with cleft palate (AOR, 2.1; 95% CI, 1.2–3.9).¹ Other investigations, including one published as recently as 2013, have not documented these same associations.³

Similarly, the combination of trimethoprim-sulfamethoxazole also has considerable appeal for treating lower UTIs in pregnancy because it is highly active against most uropathogens, is inexpensive, and usually is very well tolerated. The report by Crider and colleagues, however, was even more worrisome with respect to the possible teratogenicity of this antibiotic.¹ The authors found that use of this antibiotic in the first trimester was associated with anencephaly (AOR, 3.4; 95% CI, 1.3–8.8), coarctation of the aorta (AOR, 2.7; 95% CI, 1.3–5.6), hypoplastic left heart (AOR, 3.2; 95% CI, 1.3–7.6), choanal atresia (AOR, 8.0; 95% CI, 2.7–23.5), transverse limb deficiency (AOR, 2.5; 95% CI, 1.0–5.9), and diaphragmatic hernia (AOR, 2.4; 95% CI, 1.1–5.4). Again, other authors, using different epidemiologic methods, have not found the same associations.³

Study strengths and weaknesses

The National Birth Defects Prevention Study by Crider and colleagues was a large, well-funded, and well-designed epidemiologic study. It included more than 13,000 patients from 10 different states.

Nevertheless, the study had certain limitations.⁴ The findings are subject to recall bias because the investigators questioned patients about antibiotic use after, rather than during, pregnancy. Understandably, the investigators were not able to verify the prescriptions for antibiotics by reviewing each individual medical record. In fact, one-third of study participants were unable to recall the exact name of the antibiotic they received. The authors did not precisely distinguish between single-agent sulfonamides and the combination drug, trimethoprim-sulfamethoxazole, although it seems reasonable to assume that the majority of the prescriptions were for the latter. Finally, given the observational nature of the study, the authors could not be certain that the observed associations were due to the antibiotic, the infection for which the drug was prescribed, or another confounding factor.

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.

EXPERT COMMENTARY

Lower urinary tract infection (UTI) is one of the most common medical complications of pregnancy. Approximately 5% to 10% of all pregnant women have asymptomatic bacteriuria, which usually antedates the pregnancy and is detected at the time of the first prenatal appointment. Another 2% to 3% develop acute cystitis during pregnancy. The dominant organisms that cause lower UTIs in pregnant women are Escherichia coli, Klebsiella pneumoniae, Proteus species, group B streptococci, enterococci, and Staphylococcus saprophyticus.

One goal of treating asymptomatic bacteriuria and acute cystitis is to prevent ascending infection (pyelonephritis), which can be associated with preterm delivery, sepsis, and adult respiratory distress syndrome. Another key goal is to use an antibiotic that eradicates the uropathogen without causing harm to either the mother or fetus.

In 2009, Crider and colleagues reported that 2 of the most commonly used antibiotics for UTIs, sulfonamides and nitrofurantoin, were associated with a disturbing spectrum of birth defects.¹ Following that report, in 2011 the American College of Obstetricians and Gynecologists (ACOG) published a committee opinion that recommended against the use of these 2 agents in the first trimester of pregnancy unless other antibiotics were unlikely to be effective.²

Details of the study

Centers for Disease Control and Prevention investigators recently conducted a study to assess the effect of these ACOG recommendations on clinical practice. Ailes and co-workers used the Truven Health MarketScan Commercial Database to examine antibiotic prescriptions filled by pregnant women with UTIs.

The database included 482,917 pregnancies in 2014 eligible for analysis. A total of 7.2% (n = 34,864) of pregnant women were treated as outpatients for a UTI within the 90-day interval before the last menstrual period or during the pregnancy. Among these women, the most commonly prescribed antibiotics during the first trimester were nitrofurantoin (34.7%), ciprofloxacin (10.5%), cephalexin (10.3%), and trimethoprim-sulfamethoxazole (7.6%).

The authors concluded that 43% of women used an antibiotic (nitrofurantoin or trimethoprim-sulfamethoxazole) in the first trimester that had potential teratogenicity, despite the precautionary statement articulated in the ACOG committee opinion.²

Antibiotic-associated effects

Of all the antibiotics that could be used to treat a lower UTI in pregnancy, nitrofurantoin probably has the greatest appeal. The drug is highly concentrated in the urine and is very active against all the common uropathogens except Proteus species. It is not absorbed significantly outside the lower urinary tract, and thus it does not alter the natural flora of the bowel or vagina (such alteration would predispose the patient to antibiotic-associated diarrhea or vulvovaginal candidiasis). Nitrofurantoin is inexpensive and usually is very well tolerated.

In the National Birth Defects Prevention Study by Crider and colleagues, nitrofurantoin was associated with anophthalmia or microphthalmos (adjusted odds ratio [AOR], 3.7; 95% confidence interval [CI], 1.1–12.2), hypoplastic left heart syndrome (AOR, 4.2; 95% CI, 1.9–9.1), atrial septal defects (AOR, 1.9; 95% CI, 1.1–3.4), and cleft lip with cleft palate (AOR, 2.1; 95% CI, 1.2–3.9).¹ Other investigations, including one published as recently as 2013, have not documented these same associations.³

Similarly, the combination of trimethoprim-sulfamethoxazole also has considerable appeal for treating lower UTIs in pregnancy because it is highly active against most uropathogens, is inexpensive, and usually is very well tolerated. The report by Crider and colleagues, however, was even more worrisome with respect to the possible teratogenicity of this antibiotic.¹ The authors found that use of this antibiotic in the first trimester was associated with anencephaly (AOR, 3.4; 95% CI, 1.3–8.8), coarctation of the aorta (AOR, 2.7; 95% CI, 1.3–5.6), hypoplastic left heart (AOR, 3.2; 95% CI, 1.3–7.6), choanal atresia (AOR, 8.0; 95% CI, 2.7–23.5), transverse limb deficiency (AOR, 2.5; 95% CI, 1.0–5.9), and diaphragmatic hernia (AOR, 2.4; 95% CI, 1.1–5.4). Again, other authors, using different epidemiologic methods, have not found the same associations.³

Study strengths and weaknesses

The National Birth Defects Prevention Study by Crider and colleagues was a large, well-funded, and well-designed epidemiologic study. It included more than 13,000 patients from 10 different states.

Nevertheless, the study had certain limitations.⁴ The findings are subject to recall bias because the investigators questioned patients about antibiotic use after, rather than during, pregnancy. Understandably, the investigators were not able to verify the prescriptions for antibiotics by reviewing each individual medical record. In fact, one-third of study participants were unable to recall the exact name of the antibiotic they received. The authors did not precisely distinguish between single-agent sulfonamides and the combination drug, trimethoprim-sulfamethoxazole, although it seems reasonable to assume that the majority of the prescriptions were for the latter. Finally, given the observational nature of the study, the authors could not be certain that the observed associations were due to the antibiotic, the infection for which the drug was prescribed, or another confounding factor.

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.

EXPERT COMMENTARY

Lower urinary tract infection (UTI) is one of the most common medical complications of pregnancy. Approximately 5% to 10% of all pregnant women have asymptomatic bacteriuria, which usually antedates the pregnancy and is detected at the time of the first prenatal appointment. Another 2% to 3% develop acute cystitis during pregnancy. The dominant organisms that cause lower UTIs in pregnant women are Escherichia coli, Klebsiella pneumoniae, Proteus species, group B streptococci, enterococci, and Staphylococcus saprophyticus.

One goal of treating asymptomatic bacteriuria and acute cystitis is to prevent ascending infection (pyelonephritis), which can be associated with preterm delivery, sepsis, and adult respiratory distress syndrome. Another key goal is to use an antibiotic that eradicates the uropathogen without causing harm to either the mother or fetus.

In 2009, Crider and colleagues reported that 2 of the most commonly used antibiotics for UTIs, sulfonamides and nitrofurantoin, were associated with a disturbing spectrum of birth defects.¹ Following that report, in 2011 the American College of Obstetricians and Gynecologists (ACOG) published a committee opinion that recommended against the use of these 2 agents in the first trimester of pregnancy unless other antibiotics were unlikely to be effective.²

Details of the study

Centers for Disease Control and Prevention investigators recently conducted a study to assess the effect of these ACOG recommendations on clinical practice. Ailes and co-workers used the Truven Health MarketScan Commercial Database to examine antibiotic prescriptions filled by pregnant women with UTIs.

The database included 482,917 pregnancies in 2014 eligible for analysis. A total of 7.2% (n = 34,864) of pregnant women were treated as outpatients for a UTI within the 90-day interval before the last menstrual period or during the pregnancy. Among these women, the most commonly prescribed antibiotics during the first trimester were nitrofurantoin (34.7%), ciprofloxacin (10.5%), cephalexin (10.3%), and trimethoprim-sulfamethoxazole (7.6%).

The authors concluded that 43% of women used an antibiotic (nitrofurantoin or trimethoprim-sulfamethoxazole) in the first trimester that had potential teratogenicity, despite the precautionary statement articulated in the ACOG committee opinion.²

Antibiotic-associated effects

Of all the antibiotics that could be used to treat a lower UTI in pregnancy, nitrofurantoin probably has the greatest appeal. The drug is highly concentrated in the urine and is very active against all the common uropathogens except Proteus species. It is not absorbed significantly outside the lower urinary tract, and thus it does not alter the natural flora of the bowel or vagina (such alteration would predispose the patient to antibiotic-associated diarrhea or vulvovaginal candidiasis). Nitrofurantoin is inexpensive and usually is very well tolerated.

In the National Birth Defects Prevention Study by Crider and colleagues, nitrofurantoin was associated with anophthalmia or microphthalmos (adjusted odds ratio [AOR], 3.7; 95% confidence interval [CI], 1.1–12.2), hypoplastic left heart syndrome (AOR, 4.2; 95% CI, 1.9–9.1), atrial septal defects (AOR, 1.9; 95% CI, 1.1–3.4), and cleft lip with cleft palate (AOR, 2.1; 95% CI, 1.2–3.9).¹ Other investigations, including one published as recently as 2013, have not documented these same associations.³

Similarly, the combination of trimethoprim-sulfamethoxazole also has considerable appeal for treating lower UTIs in pregnancy because it is highly active against most uropathogens, is inexpensive, and usually is very well tolerated. The report by Crider and colleagues, however, was even more worrisome with respect to the possible teratogenicity of this antibiotic.¹ The authors found that use of this antibiotic in the first trimester was associated with anencephaly (AOR, 3.4; 95% CI, 1.3–8.8), coarctation of the aorta (AOR, 2.7; 95% CI, 1.3–5.6), hypoplastic left heart (AOR, 3.2; 95% CI, 1.3–7.6), choanal atresia (AOR, 8.0; 95% CI, 2.7–23.5), transverse limb deficiency (AOR, 2.5; 95% CI, 1.0–5.9), and diaphragmatic hernia (AOR, 2.4; 95% CI, 1.1–5.4). Again, other authors, using different epidemiologic methods, have not found the same associations.³

Study strengths and weaknesses

The National Birth Defects Prevention Study by Crider and colleagues was a large, well-funded, and well-designed epidemiologic study. It included more than 13,000 patients from 10 different states.

Nevertheless, the study had certain limitations.⁴ The findings are subject to recall bias because the investigators questioned patients about antibiotic use after, rather than during, pregnancy. Understandably, the investigators were not able to verify the prescriptions for antibiotics by reviewing each individual medical record. In fact, one-third of study participants were unable to recall the exact name of the antibiotic they received. The authors did not precisely distinguish between single-agent sulfonamides and the combination drug, trimethoprim-sulfamethoxazole, although it seems reasonable to assume that the majority of the prescriptions were for the latter. Finally, given the observational nature of the study, the authors could not be certain that the observed associations were due to the antibiotic, the infection for which the drug was prescribed, or another confounding factor.

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.

In recent decades the practice of medicine has drifted away from the performance of a physical examination during most patient encounters and evolved toward the more intensive use of history, imaging, and laboratory studies to guide management decisions. For example, it is common for a woman to present to an emergency department with abdominal or pelvic pain and undergo a computerized tomography scan before an abdominal and pelvic examination is performed. Some authorities believe that the trend to reduce the importance of the physical examination has gone way too far and resulted in a reduction in the quality of health care.^1,2

Many skin diseases only can be diagnosed by having the patient disrobe and examining the skin. Gynecologists are uniquely positioned to diagnose important skin diseases because, while performing a reproductive health examination, they may be the first clinicians to directly examine the anogenital area and inner thighs. Skin diseases that are prevalent and can be diagnosed while performing an examination of the anogenital region include lichen sclerosus (LS) and hidradenitis suppurativa (HS). The prevalence of each of these conditions is in the range of 1% to 4% of women.^3–5

Failure to examine the anogenital area and insufficient attention to the early signs of LS and HS may result in a long delay in the diagnosis.⁶ In 1 survey, of 517 patients with HS, there was a 7-year interval between the onset of the disease and the diagnosis by a clinician.⁷ Delay in diagnosis results in increased scarring, which makes it more difficult to effectively treat the disease. In this editorial, I will focus on the pathogenesis, diagnosis, and treatment of HS.

Diagnosis, presentation, and staging

Hidradenitis suppurativa (from the Greek, hidros means sweat and aden means glands) is a painful, chronic, relapsing, inflammatory skin disorder affecting the follicular unit. It is manifested by nodules, pustules, sinus tracts, and scars, usually in intertriginous areas. The diagnosis is made by history and physical examination. The 3 cardinal features of HS are 1) deep-seated nodules, comedones, and fibrosis; 2) typical anatomic location of the lesions in the axillae, inguinocrural, and anogenital regions, and 3) chronic relapsing course.⁸

Disease severity is often assessed using the Hurley staging system:

• stage I: abscess formation without sinus tracts or scarring (FIGURE)
• stage II: recurrent abscesses with tract formation and scarring, widely separated lesions
• stage III: diffuse or near-diffuse involvement or multiple interconnected tracts and abscesses.

In one report, stage I, II, and III disease was diagnosed in 65%, 31%, and 4% of cases, respectively, indicating that most HS is diagnosed instage I and suitable for treatment by a gynecologist.⁹

HS typically presents after puberty and women are more commonly affected than men. In one case series including 232 women with HS the regions most commonly affected were: axillae, inguinofemoral, urogenital, and buttocks in 79%, 77%, 51%, and 40% of cases, respectively.¹⁰ Risk factors for HS include obesity, cigarette smoking, tight fitting clothing, and chronic friction across the affected skin area.⁵

Pathogenesis

The pathophysiology of HS is thought to begin with occlusion of the follicle, resulting in follicle rupture deep in the dermis, thereby triggering inflammation, bacterial infection, and scarring. Dermal areas affected by HS have high concentrations of cytokines, including tumor necrosis factor (TNF)–alpha, interleukin (IL)-1-beta, IL-23, and IL-32.^11,12 Once HS becomes an established process, it is difficult to treat because the dermal inflammatory process and scarring provides a microenvironment that facilitates disease progression. Hence early detection and treatment may result in optimal long-term outcomes.

Read about management of HS by stage

Treatment

Many recommended treatments for HS have not been formally tested in large randomized trials. A recent Cochrane review identified only 12 high-quality trials and the median number of participants was 27 per trial.¹³ Consequently, most treatment recommendations are based on expert opinion. Recommended treatments include smoking cessation, weight loss, topical and systemic antibiotics, antiandrogens, anti-inflammatory biologics (adalimumab and infliximab), and surgery. Smoking cessation and weight loss are strongly recommended in the initial treatment of HS. Bariatric surgery and significant postprocedure weight loss has been reported to cause a reduction in disease activity.¹⁴

Stage I management. For the initial treatment of stage I HS, clindamycin gel 1% applied twice daily to affected areas is recommended.¹⁵ Recommended oral antibiotic treatments include tetracycline 500 mg twice daily for 12 weeks¹⁶ or doxycycline 100 mg or 200 mg given daily for 10 weeks or clindamycin 300 mg twice daily plus rifampicin 600 mg once daily for 10 weeks.^17,18 These antibiotics have both antimicrobial and anti-inflammatory effects.

Hormonal interventions that suppress androgen production or action may help reduce HS disease activity. For women with HS who also need contraception, an estrogen-progestin contraceptive may help reduce HS disease activity in up to 50% of individuals.¹⁹ The 5-alpha reductase inhibitor finasteride, at high doses (5 to 15 mg daily), has been reported to reduce HS disease activity.^20,21 Finasteride is a teratogen, and the FDA strongly recommends against its use by women. Spironolactone, an anti-mineralocorticoid and antiandrogen, at a dose of 100 mg daily has been reported to reduce disease activity in about 50% of treated individuals and is FDA approved for use in women.²² Among reproductive-age women, spironolactone, which is a teratogen, only should be prescribed to women using an effective form of contraceptive. HS is often associated with obesity and insulin resistance. Metformin 500 mg three times daily has been reported to decrease disease activity.^23,24

Stage II or III management. For Hurley stage II or III HS, referral to a dermatologist is warranted. There is evidence that too few people with HS are referred to a dermatologist.²⁵ For severe HS resistant to oral medications, anti-TNF monoclonal antibody treatment with adalimumab (Humira) or infliximab (Remicade) is effective. Adalimumab is administered by subcutaneous injection and is US Food and Drug Administration (FDA)–approved to treat HS. Following a loading dose, adalimumab is administered weekly at a dose of 40 mg.²⁶ Infliximab, which is not FDA approved to treat HS, is administered by intravenous infusion at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks.²⁷

Surgical management. HS is sometimes treated surgically with laser destruction of lesions, punch debridement, or wide excision of diseased tissue.^28,29 There are no high quality clinical trials of surgical treatment of HS. Punch debridement can be performed using a 5- to 7-mm circular skin punch to deeply excise the inflamed follicle. Wide excision can be followed by wound closure with advancement flaps or split-thickness skin grafting. Wound closure by secondary intention is possible but requires many weeks or months of burdensome dressing changes to complete the healing process. Recurrence is common following surgical therapy and ranges from 30% with deroofing or laser treatment to 6% following wide excision and skin graft closure of the wound.³⁰

Physical examination vital to early diagnosis

Delay in diagnosis of an active disease process has many causes, including nonperformance of a physical examination. In a web-based survey of physicians’ experiences with oversights related to the physical examination, 3 problems frequently reported were: nonperformance of any portion of the physical examination, failure to undress the patient to examine the skin, and failure to examine the abdomen and anogenital region in a patient with abdominal or pelvic pain.³¹ Oversights in the physical examination frequently caused a delay in diagnosis and treatment. With both LS and HS, patients may not recognize that they have a skin disease, or they may be embarrassed to show a clinician a skin change they have noticed. Early diagnosis and treatment are essential to achieving a good outcome and make a tremendous difference in the quality of life for the patient. Physical examination is a skill we have learned through diligent study and experience in practice. We can use these skills to greatly improve the lives of our patients.

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.

In recent decades the practice of medicine has drifted away from the performance of a physical examination during most patient encounters and evolved toward the more intensive use of history, imaging, and laboratory studies to guide management decisions. For example, it is common for a woman to present to an emergency department with abdominal or pelvic pain and undergo a computerized tomography scan before an abdominal and pelvic examination is performed. Some authorities believe that the trend to reduce the importance of the physical examination has gone way too far and resulted in a reduction in the quality of health care.^1,2

Many skin diseases only can be diagnosed by having the patient disrobe and examining the skin. Gynecologists are uniquely positioned to diagnose important skin diseases because, while performing a reproductive health examination, they may be the first clinicians to directly examine the anogenital area and inner thighs. Skin diseases that are prevalent and can be diagnosed while performing an examination of the anogenital region include lichen sclerosus (LS) and hidradenitis suppurativa (HS). The prevalence of each of these conditions is in the range of 1% to 4% of women.^3–5

Failure to examine the anogenital area and insufficient attention to the early signs of LS and HS may result in a long delay in the diagnosis.⁶ In 1 survey, of 517 patients with HS, there was a 7-year interval between the onset of the disease and the diagnosis by a clinician.⁷ Delay in diagnosis results in increased scarring, which makes it more difficult to effectively treat the disease. In this editorial, I will focus on the pathogenesis, diagnosis, and treatment of HS.

Diagnosis, presentation, and staging

Hidradenitis suppurativa (from the Greek, hidros means sweat and aden means glands) is a painful, chronic, relapsing, inflammatory skin disorder affecting the follicular unit. It is manifested by nodules, pustules, sinus tracts, and scars, usually in intertriginous areas. The diagnosis is made by history and physical examination. The 3 cardinal features of HS are 1) deep-seated nodules, comedones, and fibrosis; 2) typical anatomic location of the lesions in the axillae, inguinocrural, and anogenital regions, and 3) chronic relapsing course.⁸

Disease severity is often assessed using the Hurley staging system:

• stage I: abscess formation without sinus tracts or scarring (FIGURE)
• stage II: recurrent abscesses with tract formation and scarring, widely separated lesions
• stage III: diffuse or near-diffuse involvement or multiple interconnected tracts and abscesses.

In one report, stage I, II, and III disease was diagnosed in 65%, 31%, and 4% of cases, respectively, indicating that most HS is diagnosed instage I and suitable for treatment by a gynecologist.⁹

HS typically presents after puberty and women are more commonly affected than men. In one case series including 232 women with HS the regions most commonly affected were: axillae, inguinofemoral, urogenital, and buttocks in 79%, 77%, 51%, and 40% of cases, respectively.¹⁰ Risk factors for HS include obesity, cigarette smoking, tight fitting clothing, and chronic friction across the affected skin area.⁵

Pathogenesis

The pathophysiology of HS is thought to begin with occlusion of the follicle, resulting in follicle rupture deep in the dermis, thereby triggering inflammation, bacterial infection, and scarring. Dermal areas affected by HS have high concentrations of cytokines, including tumor necrosis factor (TNF)–alpha, interleukin (IL)-1-beta, IL-23, and IL-32.^11,12 Once HS becomes an established process, it is difficult to treat because the dermal inflammatory process and scarring provides a microenvironment that facilitates disease progression. Hence early detection and treatment may result in optimal long-term outcomes.

Read about management of HS by stage

Treatment

Many recommended treatments for HS have not been formally tested in large randomized trials. A recent Cochrane review identified only 12 high-quality trials and the median number of participants was 27 per trial.¹³ Consequently, most treatment recommendations are based on expert opinion. Recommended treatments include smoking cessation, weight loss, topical and systemic antibiotics, antiandrogens, anti-inflammatory biologics (adalimumab and infliximab), and surgery. Smoking cessation and weight loss are strongly recommended in the initial treatment of HS. Bariatric surgery and significant postprocedure weight loss has been reported to cause a reduction in disease activity.¹⁴

Stage I management. For the initial treatment of stage I HS, clindamycin gel 1% applied twice daily to affected areas is recommended.¹⁵ Recommended oral antibiotic treatments include tetracycline 500 mg twice daily for 12 weeks¹⁶ or doxycycline 100 mg or 200 mg given daily for 10 weeks or clindamycin 300 mg twice daily plus rifampicin 600 mg once daily for 10 weeks.^17,18 These antibiotics have both antimicrobial and anti-inflammatory effects.

Hormonal interventions that suppress androgen production or action may help reduce HS disease activity. For women with HS who also need contraception, an estrogen-progestin contraceptive may help reduce HS disease activity in up to 50% of individuals.¹⁹ The 5-alpha reductase inhibitor finasteride, at high doses (5 to 15 mg daily), has been reported to reduce HS disease activity.^20,21 Finasteride is a teratogen, and the FDA strongly recommends against its use by women. Spironolactone, an anti-mineralocorticoid and antiandrogen, at a dose of 100 mg daily has been reported to reduce disease activity in about 50% of treated individuals and is FDA approved for use in women.²² Among reproductive-age women, spironolactone, which is a teratogen, only should be prescribed to women using an effective form of contraceptive. HS is often associated with obesity and insulin resistance. Metformin 500 mg three times daily has been reported to decrease disease activity.^23,24

Stage II or III management. For Hurley stage II or III HS, referral to a dermatologist is warranted. There is evidence that too few people with HS are referred to a dermatologist.²⁵ For severe HS resistant to oral medications, anti-TNF monoclonal antibody treatment with adalimumab (Humira) or infliximab (Remicade) is effective. Adalimumab is administered by subcutaneous injection and is US Food and Drug Administration (FDA)–approved to treat HS. Following a loading dose, adalimumab is administered weekly at a dose of 40 mg.²⁶ Infliximab, which is not FDA approved to treat HS, is administered by intravenous infusion at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks.²⁷

Surgical management. HS is sometimes treated surgically with laser destruction of lesions, punch debridement, or wide excision of diseased tissue.^28,29 There are no high quality clinical trials of surgical treatment of HS. Punch debridement can be performed using a 5- to 7-mm circular skin punch to deeply excise the inflamed follicle. Wide excision can be followed by wound closure with advancement flaps or split-thickness skin grafting. Wound closure by secondary intention is possible but requires many weeks or months of burdensome dressing changes to complete the healing process. Recurrence is common following surgical therapy and ranges from 30% with deroofing or laser treatment to 6% following wide excision and skin graft closure of the wound.³⁰

Physical examination vital to early diagnosis

Delay in diagnosis of an active disease process has many causes, including nonperformance of a physical examination. In a web-based survey of physicians’ experiences with oversights related to the physical examination, 3 problems frequently reported were: nonperformance of any portion of the physical examination, failure to undress the patient to examine the skin, and failure to examine the abdomen and anogenital region in a patient with abdominal or pelvic pain.³¹ Oversights in the physical examination frequently caused a delay in diagnosis and treatment. With both LS and HS, patients may not recognize that they have a skin disease, or they may be embarrassed to show a clinician a skin change they have noticed. Early diagnosis and treatment are essential to achieving a good outcome and make a tremendous difference in the quality of life for the patient. Physical examination is a skill we have learned through diligent study and experience in practice. We can use these skills to greatly improve the lives of our patients.

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.

In recent decades the practice of medicine has drifted away from the performance of a physical examination during most patient encounters and evolved toward the more intensive use of history, imaging, and laboratory studies to guide management decisions. For example, it is common for a woman to present to an emergency department with abdominal or pelvic pain and undergo a computerized tomography scan before an abdominal and pelvic examination is performed. Some authorities believe that the trend to reduce the importance of the physical examination has gone way too far and resulted in a reduction in the quality of health care.^1,2

Many skin diseases only can be diagnosed by having the patient disrobe and examining the skin. Gynecologists are uniquely positioned to diagnose important skin diseases because, while performing a reproductive health examination, they may be the first clinicians to directly examine the anogenital area and inner thighs. Skin diseases that are prevalent and can be diagnosed while performing an examination of the anogenital region include lichen sclerosus (LS) and hidradenitis suppurativa (HS). The prevalence of each of these conditions is in the range of 1% to 4% of women.^3–5

Failure to examine the anogenital area and insufficient attention to the early signs of LS and HS may result in a long delay in the diagnosis.⁶ In 1 survey, of 517 patients with HS, there was a 7-year interval between the onset of the disease and the diagnosis by a clinician.⁷ Delay in diagnosis results in increased scarring, which makes it more difficult to effectively treat the disease. In this editorial, I will focus on the pathogenesis, diagnosis, and treatment of HS.

Diagnosis, presentation, and staging

Hidradenitis suppurativa (from the Greek, hidros means sweat and aden means glands) is a painful, chronic, relapsing, inflammatory skin disorder affecting the follicular unit. It is manifested by nodules, pustules, sinus tracts, and scars, usually in intertriginous areas. The diagnosis is made by history and physical examination. The 3 cardinal features of HS are 1) deep-seated nodules, comedones, and fibrosis; 2) typical anatomic location of the lesions in the axillae, inguinocrural, and anogenital regions, and 3) chronic relapsing course.⁸

Disease severity is often assessed using the Hurley staging system:

• stage I: abscess formation without sinus tracts or scarring (FIGURE)
• stage II: recurrent abscesses with tract formation and scarring, widely separated lesions
• stage III: diffuse or near-diffuse involvement or multiple interconnected tracts and abscesses.

In one report, stage I, II, and III disease was diagnosed in 65%, 31%, and 4% of cases, respectively, indicating that most HS is diagnosed instage I and suitable for treatment by a gynecologist.⁹

HS typically presents after puberty and women are more commonly affected than men. In one case series including 232 women with HS the regions most commonly affected were: axillae, inguinofemoral, urogenital, and buttocks in 79%, 77%, 51%, and 40% of cases, respectively.¹⁰ Risk factors for HS include obesity, cigarette smoking, tight fitting clothing, and chronic friction across the affected skin area.⁵

Pathogenesis

The pathophysiology of HS is thought to begin with occlusion of the follicle, resulting in follicle rupture deep in the dermis, thereby triggering inflammation, bacterial infection, and scarring. Dermal areas affected by HS have high concentrations of cytokines, including tumor necrosis factor (TNF)–alpha, interleukin (IL)-1-beta, IL-23, and IL-32.^11,12 Once HS becomes an established process, it is difficult to treat because the dermal inflammatory process and scarring provides a microenvironment that facilitates disease progression. Hence early detection and treatment may result in optimal long-term outcomes.

Read about management of HS by stage

Treatment

Many recommended treatments for HS have not been formally tested in large randomized trials. A recent Cochrane review identified only 12 high-quality trials and the median number of participants was 27 per trial.¹³ Consequently, most treatment recommendations are based on expert opinion. Recommended treatments include smoking cessation, weight loss, topical and systemic antibiotics, antiandrogens, anti-inflammatory biologics (adalimumab and infliximab), and surgery. Smoking cessation and weight loss are strongly recommended in the initial treatment of HS. Bariatric surgery and significant postprocedure weight loss has been reported to cause a reduction in disease activity.¹⁴

Stage I management. For the initial treatment of stage I HS, clindamycin gel 1% applied twice daily to affected areas is recommended.¹⁵ Recommended oral antibiotic treatments include tetracycline 500 mg twice daily for 12 weeks¹⁶ or doxycycline 100 mg or 200 mg given daily for 10 weeks or clindamycin 300 mg twice daily plus rifampicin 600 mg once daily for 10 weeks.^17,18 These antibiotics have both antimicrobial and anti-inflammatory effects.

Hormonal interventions that suppress androgen production or action may help reduce HS disease activity. For women with HS who also need contraception, an estrogen-progestin contraceptive may help reduce HS disease activity in up to 50% of individuals.¹⁹ The 5-alpha reductase inhibitor finasteride, at high doses (5 to 15 mg daily), has been reported to reduce HS disease activity.^20,21 Finasteride is a teratogen, and the FDA strongly recommends against its use by women. Spironolactone, an anti-mineralocorticoid and antiandrogen, at a dose of 100 mg daily has been reported to reduce disease activity in about 50% of treated individuals and is FDA approved for use in women.²² Among reproductive-age women, spironolactone, which is a teratogen, only should be prescribed to women using an effective form of contraceptive. HS is often associated with obesity and insulin resistance. Metformin 500 mg three times daily has been reported to decrease disease activity.^23,24

Stage II or III management. For Hurley stage II or III HS, referral to a dermatologist is warranted. There is evidence that too few people with HS are referred to a dermatologist.²⁵ For severe HS resistant to oral medications, anti-TNF monoclonal antibody treatment with adalimumab (Humira) or infliximab (Remicade) is effective. Adalimumab is administered by subcutaneous injection and is US Food and Drug Administration (FDA)–approved to treat HS. Following a loading dose, adalimumab is administered weekly at a dose of 40 mg.²⁶ Infliximab, which is not FDA approved to treat HS, is administered by intravenous infusion at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 8 weeks.²⁷

Surgical management. HS is sometimes treated surgically with laser destruction of lesions, punch debridement, or wide excision of diseased tissue.^28,29 There are no high quality clinical trials of surgical treatment of HS. Punch debridement can be performed using a 5- to 7-mm circular skin punch to deeply excise the inflamed follicle. Wide excision can be followed by wound closure with advancement flaps or split-thickness skin grafting. Wound closure by secondary intention is possible but requires many weeks or months of burdensome dressing changes to complete the healing process. Recurrence is common following surgical therapy and ranges from 30% with deroofing or laser treatment to 6% following wide excision and skin graft closure of the wound.³⁰

Physical examination vital to early diagnosis

Delay in diagnosis of an active disease process has many causes, including nonperformance of a physical examination. In a web-based survey of physicians’ experiences with oversights related to the physical examination, 3 problems frequently reported were: nonperformance of any portion of the physical examination, failure to undress the patient to examine the skin, and failure to examine the abdomen and anogenital region in a patient with abdominal or pelvic pain.³¹ Oversights in the physical examination frequently caused a delay in diagnosis and treatment. With both LS and HS, patients may not recognize that they have a skin disease, or they may be embarrassed to show a clinician a skin change they have noticed. Early diagnosis and treatment are essential to achieving a good outcome and make a tremendous difference in the quality of life for the patient. Physical examination is a skill we have learned through diligent study and experience in practice. We can use these skills to greatly improve the lives of our patients.

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.

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

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.

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

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.

The American College of Obstetricians and Gynecologists (ACOG) is a nonprofit organization of women’s health care physicians advocating the highest standards of practice, continuing member education, and public awareness of women’s health care issues.¹ The organization has long recognized the impact that social media and mobile technology would have for itself as well as its membership. ACOG published a Social Media Guide in 2012, featuring a section on how to use apps in ObGyn practice and provided a list of apps for ObGyns and their patients.²

ACOG introduced its own app 4 years ago and has since updated the app several times, most recently on December 6, 2017. The ACOG app has a useful search function, a home button, and a place for users to email feedback (TABLE 1). The app most importantly contains several applets (small applications designed to perform a specific function within the main application). These applets encompass 3 types of apps for health care providers: clinical decision-making apps (Practice Bulletins, Committee Opinions, an Estimated Due Date Calculator that was featured in a prior review,³ Indicated Delivery, and Immunize) (TABLE 2), reference and information gathering apps (Today’s Headlines), and member support apps (ACOG Contacts, Careers, Annual Meeting, Districts, Council on Resident Education in Obstetrics and Gynecology [CREOG], and Website).⁴

This review will focus on the main ACOG app, which is evaluated by a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, and important special features).⁵ In addition, the clinical decision-making applets will be highlighted in a second table. I commend ACOG for developing these useful tools to augment their members’ practices. Of note, for the Practice Bulletins and Indicated Delivery applets, users will need to input their ACOG log-in access information.

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.

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

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.

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

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.

An either/or choice is not a good strategy for pain

I found Dr. Barbieri’s editorial on postpartum opioid use and breastfeeding interesting, but one key issue was not addressed: Following this guidance means that new mothers have to choose between breastfeeding and pain control. You may explain to a patient with 2-day cesarean delivery pain, “If you take pain medicine while breastfeeding, it can adversely affect the baby. So we will give you acetaminophen.” While some moms will deal with it, others will stop breastfeeding. With the increasing pressure to advocate for breastfeeding, this strategy is likely not realistic.

R. Lee Toler, DO
Bolivia, North Carolina

My pain management protocol

While presently in an office-based setting, back in my inpatient practice days I would order oxycodone plus acetaminophen for 1 to 2 days postoperative cesarean delivery, and only 1 day after normal spontaneous delivery if the patient had a large perineal repair or multiparous involution pain. Otherwise, it was ibuprofen 800 mg, then 400 to 600 mg on discharge home.

Gabrielle Long, CNM
Mohegan Lake, New York

Respect women’s postsurgical pain management needs

There is a real disrespect for pain control for women, such as after a cesarean delivery. I would like to see any male have major surgery through a large muscle like the uterus and not need significant pain control options!

Anne V. Hale, MD
El Paso, Texas

Dr. Barbieri responds

I agree with Ms. Long that most postpartum patients, including many who have had a cesarean delivery, can achieve adequate pain control with the use of parenteral and oral nonsteroidal anti-inflammatory drugs (NSAIDs) and oral acetaminophen. Drs. Toler and Hale are concerned that postpartum pain control might be suboptimal if opioids are underprescribed. However, in many developed countries obstetricians do not use opioid pain medicine for postpartum pain management, relying on NSAIDs and acetaminophen. Given the success of this approach, I think we can significantly reduce the use of opioids by postpartum women in the United States by optimizing our use of nonopioid medications.

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.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

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.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

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.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

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.