Perspectives

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

On April 4, 2021, a rule implementing the federal regulations of the Information Blocking 21st Century Cures Act will be enacted. This Act furthers the seamless release of medical records to promote improved outcomes, access to medical information, and transparency of costs. These regulations, although important, may impact the ability to offer confidentiality to adolescents seeking care for sensitive issues. Each state will need to be thoughtful balancing the action or inaction of allowing access to confidential or sensitive progress notes, as interference with access may be considered information blocking and subject to penalties and fines.

belchonock/Thinkstock

With adolescent confidential notes, protection rules may not apply under the information blocking regulations. These regulations will release progress notes, imaging narratives, procedure notes, and labs to parents via their EHR portals. The release of information is not limited, and both inpatient and outpatient records will be released. These regulations are written for adults with the assumption that all information is released to the individual receiving the care and shared with outside providers.

Ms. Thew is medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee. She is a member of the Pediatric News editorial advisory board. She had no relevant financial disclosures. Email Ms. Thew at pdnews@mdedge.com.

Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.

To better understand these developments, this news organization reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, in Baltimore, Maryland. This interview has been edited for length and clarity.

There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?Dr. Stone: The number of new cases in the United States has actually been declining over the past 2 decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.

What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?

The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.

p53 gene mutations are thought to occur early in the evolution of ovarian cancer. There are data indicating that these mutations actually occur in cells lining the fallopian tubes. Polymerase chain reaction–based DNA/gene sequencing performed on cervical fluid collected by Pap smears could detect these p53-mutated cells shed from the fallopian tubes.

A strength of this study is that it included healthy controls. None of their Pap smears screened positive for the p53 mutations, unlike the Pap smears of women predating their diagnosis of ovarian cancer. Limitations of the study include the fact that it had a small sample size. Findings will need to be confirmed in a larger patient population.

Also, the study only looked for p53 gene mutations. Ovarian cancers, like other cancers, are largely thought to occur when there is a buildup of mutations in critical genes that result in uncontrolled cell growth and division. These genetic changes/mutations are acquired during a person’s lifetime. Thus, there are likely early genetic changes/mutations that occur in addition to p53 mutations that ultimately lead to the development of ovarian cancer. Detecting these along with p53 mutations could improve the sensitivity/detection rate of the screening strategy that the authors are investigating.

Finally, this screening strategy may not prove effective for the early detection of all histologic subtypes of epithelial ovarian cancer or for nonepithelial ovarian cancers.

What other recent developments in the diagnosis of ovarian cancer should clinicians be aware of?

Liquid biopsies using circulating tumor DNA (ctDNA) have shown promising results for cancer detection and management, including ovarian cancer. However, further clarification is needed to define the minimum tumor size/burden detectable using ctDNA-based approaches. Moreover, large prospective studies are needed to determine the clinical utility of ctDNA detection for early diagnosis of ovarian cancer and its impact on patient outcomes.

DNA methylation is an early event in carcinogenesis and can be detected in blood plasma samples from cancer patients. Data related to the discovery and validation of discriminated methylated DNA marker candidates extracted from ovarian cancer tissues were presented at the American Society of Clinical Oncology meeting this year. Findings were subsequently evaluated in plasma from women with and without ovarian cancer.

In addition to blood, peritoneal fluid and uterine lavage have been used to obtain cell pellets that are used for the identification of common mutant genes – TP53, BRCA1, and BRCA2. These body fluids have also been shown as the source of tumor-derived material that can be used to differentiate between ovarian cancer patients and healthy individuals.

Further studies are needed to determine the sensitivity and specificity of other noninvasive tests for the diagnosis of ovarian cancer.

The American Cancer Society issued a statement that the human papillomavirus (HPV) test is the preferred cervical cancer screening tool. Why do they prefer the HPV test over the Pap test?

The American Cancer Society recommends that cervical cancer testing (screening) begin at age 25 years. Women aged 25-65 years should have a primary HPV test every 5 years. If primary HPV testing is not available, screening may be done with either a co-test that combines an HPV test with a Pap test every 5 years or a Pap test alone every 3 years.

The HPV test is widely available. The cost of an HPV test is approximately $44 (unit cost, 2014 USD). The cost of a Pap test is approximately $30 (unit cost, 2014 USD).

The HPV test is preferred over cytologic testing (Pap) for several reasons.

Firstly, in well-designed studies, the sensitivity of a single Pap smear for detecting high-grade precancer of the cervix is around 50%, which is less than optimal for a cancer screening test. Sensitivity means the chance that, if you have the disease (in this case, high-grade precancer of the cervix), the test will detect it. In particular, cytology is known to have an even more limited ability to detect glandular precancers, which arise in the endocervical canal rather than on or in close proximity to the exterior surface of the cervix (ectocervix). Thus, HPV-based screening programs hold the promise of improving detection of cervical adenocarcinoma.

Secondly, to function reliably, cytology programs require substantial infrastructure, highly qualified human resources, and a well‐defined quality-control system, which have proved to be costly and difficult to implement. This results in global disparities in cytology-based cervical cancer screening programs.

Thirdly, although co‐testing with both cytology and HPV tests is an option for screening programs, studies have confirmed that there is limited benefit from adding cytology to HPV screening. Long‐term studies from Kaiser Permanente that included over 1 million women found that HPV testing has a very high negative predictive value for precancerous lesions. Women with negative HPV tests were very unlikely to develop precancerous lesions in the following 5 years. The 5‐year risk of high-grade precancer or cancer of the cervix following a negative HPV test was 0.14%, whereas for women with a negative cytology, it was 0.31%. The screening benefit of co‐testing is largely driven by HPV testing and not cytology.

So, in summary, HPV testing is preferred over cytologic screening for cervical cancer, given its improved sensitivity and quality assurance, the opportunity to automate testing, and ultimately, its prospect of reducing the overall number of lifetime screenings for women.


Dr. Stone has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.

To better understand these developments, this news organization reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, in Baltimore, Maryland. This interview has been edited for length and clarity.

There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?Dr. Stone: The number of new cases in the United States has actually been declining over the past 2 decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.

What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?

The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.

p53 gene mutations are thought to occur early in the evolution of ovarian cancer. There are data indicating that these mutations actually occur in cells lining the fallopian tubes. Polymerase chain reaction–based DNA/gene sequencing performed on cervical fluid collected by Pap smears could detect these p53-mutated cells shed from the fallopian tubes.

A strength of this study is that it included healthy controls. None of their Pap smears screened positive for the p53 mutations, unlike the Pap smears of women predating their diagnosis of ovarian cancer. Limitations of the study include the fact that it had a small sample size. Findings will need to be confirmed in a larger patient population.

Also, the study only looked for p53 gene mutations. Ovarian cancers, like other cancers, are largely thought to occur when there is a buildup of mutations in critical genes that result in uncontrolled cell growth and division. These genetic changes/mutations are acquired during a person’s lifetime. Thus, there are likely early genetic changes/mutations that occur in addition to p53 mutations that ultimately lead to the development of ovarian cancer. Detecting these along with p53 mutations could improve the sensitivity/detection rate of the screening strategy that the authors are investigating.

Finally, this screening strategy may not prove effective for the early detection of all histologic subtypes of epithelial ovarian cancer or for nonepithelial ovarian cancers.

What other recent developments in the diagnosis of ovarian cancer should clinicians be aware of?

Liquid biopsies using circulating tumor DNA (ctDNA) have shown promising results for cancer detection and management, including ovarian cancer. However, further clarification is needed to define the minimum tumor size/burden detectable using ctDNA-based approaches. Moreover, large prospective studies are needed to determine the clinical utility of ctDNA detection for early diagnosis of ovarian cancer and its impact on patient outcomes.

DNA methylation is an early event in carcinogenesis and can be detected in blood plasma samples from cancer patients. Data related to the discovery and validation of discriminated methylated DNA marker candidates extracted from ovarian cancer tissues were presented at the American Society of Clinical Oncology meeting this year. Findings were subsequently evaluated in plasma from women with and without ovarian cancer.

In addition to blood, peritoneal fluid and uterine lavage have been used to obtain cell pellets that are used for the identification of common mutant genes – TP53, BRCA1, and BRCA2. These body fluids have also been shown as the source of tumor-derived material that can be used to differentiate between ovarian cancer patients and healthy individuals.

Further studies are needed to determine the sensitivity and specificity of other noninvasive tests for the diagnosis of ovarian cancer.

The American Cancer Society issued a statement that the human papillomavirus (HPV) test is the preferred cervical cancer screening tool. Why do they prefer the HPV test over the Pap test?

The American Cancer Society recommends that cervical cancer testing (screening) begin at age 25 years. Women aged 25-65 years should have a primary HPV test every 5 years. If primary HPV testing is not available, screening may be done with either a co-test that combines an HPV test with a Pap test every 5 years or a Pap test alone every 3 years.

The HPV test is widely available. The cost of an HPV test is approximately $44 (unit cost, 2014 USD). The cost of a Pap test is approximately $30 (unit cost, 2014 USD).

The HPV test is preferred over cytologic testing (Pap) for several reasons.

Firstly, in well-designed studies, the sensitivity of a single Pap smear for detecting high-grade precancer of the cervix is around 50%, which is less than optimal for a cancer screening test. Sensitivity means the chance that, if you have the disease (in this case, high-grade precancer of the cervix), the test will detect it. In particular, cytology is known to have an even more limited ability to detect glandular precancers, which arise in the endocervical canal rather than on or in close proximity to the exterior surface of the cervix (ectocervix). Thus, HPV-based screening programs hold the promise of improving detection of cervical adenocarcinoma.

Secondly, to function reliably, cytology programs require substantial infrastructure, highly qualified human resources, and a well‐defined quality-control system, which have proved to be costly and difficult to implement. This results in global disparities in cytology-based cervical cancer screening programs.

Thirdly, although co‐testing with both cytology and HPV tests is an option for screening programs, studies have confirmed that there is limited benefit from adding cytology to HPV screening. Long‐term studies from Kaiser Permanente that included over 1 million women found that HPV testing has a very high negative predictive value for precancerous lesions. Women with negative HPV tests were very unlikely to develop precancerous lesions in the following 5 years. The 5‐year risk of high-grade precancer or cancer of the cervix following a negative HPV test was 0.14%, whereas for women with a negative cytology, it was 0.31%. The screening benefit of co‐testing is largely driven by HPV testing and not cytology.

So, in summary, HPV testing is preferred over cytologic screening for cervical cancer, given its improved sensitivity and quality assurance, the opportunity to automate testing, and ultimately, its prospect of reducing the overall number of lifetime screenings for women.


Dr. Stone has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.

To better understand these developments, this news organization reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, in Baltimore, Maryland. This interview has been edited for length and clarity.

There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?Dr. Stone: The number of new cases in the United States has actually been declining over the past 2 decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.

What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?

The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.

p53 gene mutations are thought to occur early in the evolution of ovarian cancer. There are data indicating that these mutations actually occur in cells lining the fallopian tubes. Polymerase chain reaction–based DNA/gene sequencing performed on cervical fluid collected by Pap smears could detect these p53-mutated cells shed from the fallopian tubes.

A strength of this study is that it included healthy controls. None of their Pap smears screened positive for the p53 mutations, unlike the Pap smears of women predating their diagnosis of ovarian cancer. Limitations of the study include the fact that it had a small sample size. Findings will need to be confirmed in a larger patient population.

Also, the study only looked for p53 gene mutations. Ovarian cancers, like other cancers, are largely thought to occur when there is a buildup of mutations in critical genes that result in uncontrolled cell growth and division. These genetic changes/mutations are acquired during a person’s lifetime. Thus, there are likely early genetic changes/mutations that occur in addition to p53 mutations that ultimately lead to the development of ovarian cancer. Detecting these along with p53 mutations could improve the sensitivity/detection rate of the screening strategy that the authors are investigating.

Finally, this screening strategy may not prove effective for the early detection of all histologic subtypes of epithelial ovarian cancer or for nonepithelial ovarian cancers.

What other recent developments in the diagnosis of ovarian cancer should clinicians be aware of?

Liquid biopsies using circulating tumor DNA (ctDNA) have shown promising results for cancer detection and management, including ovarian cancer. However, further clarification is needed to define the minimum tumor size/burden detectable using ctDNA-based approaches. Moreover, large prospective studies are needed to determine the clinical utility of ctDNA detection for early diagnosis of ovarian cancer and its impact on patient outcomes.

DNA methylation is an early event in carcinogenesis and can be detected in blood plasma samples from cancer patients. Data related to the discovery and validation of discriminated methylated DNA marker candidates extracted from ovarian cancer tissues were presented at the American Society of Clinical Oncology meeting this year. Findings were subsequently evaluated in plasma from women with and without ovarian cancer.

In addition to blood, peritoneal fluid and uterine lavage have been used to obtain cell pellets that are used for the identification of common mutant genes – TP53, BRCA1, and BRCA2. These body fluids have also been shown as the source of tumor-derived material that can be used to differentiate between ovarian cancer patients and healthy individuals.

Further studies are needed to determine the sensitivity and specificity of other noninvasive tests for the diagnosis of ovarian cancer.

The American Cancer Society issued a statement that the human papillomavirus (HPV) test is the preferred cervical cancer screening tool. Why do they prefer the HPV test over the Pap test?

The American Cancer Society recommends that cervical cancer testing (screening) begin at age 25 years. Women aged 25-65 years should have a primary HPV test every 5 years. If primary HPV testing is not available, screening may be done with either a co-test that combines an HPV test with a Pap test every 5 years or a Pap test alone every 3 years.

The HPV test is widely available. The cost of an HPV test is approximately $44 (unit cost, 2014 USD). The cost of a Pap test is approximately $30 (unit cost, 2014 USD).

The HPV test is preferred over cytologic testing (Pap) for several reasons.

Firstly, in well-designed studies, the sensitivity of a single Pap smear for detecting high-grade precancer of the cervix is around 50%, which is less than optimal for a cancer screening test. Sensitivity means the chance that, if you have the disease (in this case, high-grade precancer of the cervix), the test will detect it. In particular, cytology is known to have an even more limited ability to detect glandular precancers, which arise in the endocervical canal rather than on or in close proximity to the exterior surface of the cervix (ectocervix). Thus, HPV-based screening programs hold the promise of improving detection of cervical adenocarcinoma.

Secondly, to function reliably, cytology programs require substantial infrastructure, highly qualified human resources, and a well‐defined quality-control system, which have proved to be costly and difficult to implement. This results in global disparities in cytology-based cervical cancer screening programs.

Thirdly, although co‐testing with both cytology and HPV tests is an option for screening programs, studies have confirmed that there is limited benefit from adding cytology to HPV screening. Long‐term studies from Kaiser Permanente that included over 1 million women found that HPV testing has a very high negative predictive value for precancerous lesions. Women with negative HPV tests were very unlikely to develop precancerous lesions in the following 5 years. The 5‐year risk of high-grade precancer or cancer of the cervix following a negative HPV test was 0.14%, whereas for women with a negative cytology, it was 0.31%. The screening benefit of co‐testing is largely driven by HPV testing and not cytology.

So, in summary, HPV testing is preferred over cytologic screening for cervical cancer, given its improved sensitivity and quality assurance, the opportunity to automate testing, and ultimately, its prospect of reducing the overall number of lifetime screenings for women.


Dr. Stone has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The treatment of ovarian cancer has evolved considerably in the last few years, with the approval of several PARP inhibitors, antiangiogenic agents, and other therapies for a multitude of indications. Additional treatments are likely to soon join this already diverse spectrum of available options, if their promising efficacy and safety continues to be borne out in ongoing research.

To better understand the individual merits and potential drawbacks of these treatments, Medscape recently spoke with Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, Baltimore. This interview has been edited for length and clarity.

Medscape: We’re starting to see preliminary data on pamiparib , an investigational inhibitor of PARP1 and PARP2, for the treatment of ovarian cancer. What is the evidence supporting this drug?

Dr. Stone: Currently, six different PARP inhibitors – olaparib, rucaparib, veliparib, niraparib, talazoparib, and pamiparib – have been in clinical development at different stages. In clinical applications, PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, have demonstrated sustained antitumor responses as single agents in patients with BRCA1 or BRCA2 mutations. Those with Food and Drug Administration indications in ovarian cancer include olaparib, rucaparib, and niraparib. The preclinical and clinical data with pamiparib is limited as of now. But, in a xenograft breast cancer model, it was found to be over 10 times more potent than olaparib.

If approved, where would pamiparib fit in the treatment paradigm for ovarian cancer?

It would potentially fit as monotherapy as well as in combination with agents other than standard chemotherapy for the treatment of BRCA mutated ovarian cancer. It could also be considered for maintenance therapy at the conclusion of chemotherapy treatment of newly diagnosed or recurrent BRCA-mutated ovarian cancer.

What adverse events are associated with pamiparib? How does the toxicity profile compare with other drugs for ovarian cancer?

With respect to PARP inhibitors, the differences in potency (PARP trapping) correlate with their toxicity profiles. The most common adverse events are gastrointestinal, hematologic, and constitutional (fatigue). Even though it is difficult to compare toxicities across different trials with heterogeneous patient populations, there are a few points worth noting.

Rucaparib leads to inhibition of renal transporter proteins involved in secretion of creatinine and can lead to increased creatinine (any grade: 15%; grade 3: ≤1%). Transaminitis is generally self-limiting and highest with rucaparib (any grade: 34%; grade 3: 10%). Hematologic toxicities are the highest with niraparib (any grade: thrombocytopenia 61%, anemia 50%, neutropenia 30%; grade ≥3: thrombocytopenia 34%, anemia 25%, neutropenia 20%).

Toxicities are more common in the first few cycles of treatment, warranting closer early monitoring. This differs somewhat from the gastrointestinal, hematological, and constitutional (fatigue) adverse events that we see with common chemotherapeutic agents used to treat ovarian cancer, which are generally cumulative.

PARP inhibitor treatment is also associated with an increased risk of developing myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). That being said, therapy-related MDS/AML is a well-recognized complication of conventional chemotherapy used to treat a variety of primary malignancies, including ovarian cancer.

The expected toxicity profile for pamiparib is based on what we have seen with the other PARP inhibitors. This includes any grade nausea (50%), fatigue (33%), anemia (20%), vomiting (15%), and neutropenia (13%). Toxicity of grade 3 or higher includes anemia (13%), neutropenia (8%), and fatigue (5%).

Where do the newest drugs to be approved for ovarian cancer in recent years fit within the treatment paradigm? What do the research findings show about their efficacy and safety?

Data from phase 2/3 trials support the use of PARP inhibitors as monotherapy as well as in combination with other agents (most commonly agents other than standard chemotherapy) for the treatment of BRCA mutated or otherwise homologous recombination-deficient (HRD) ovarian cancer. They can also be considered for maintenance therapy at the conclusion of treatment of newly diagnosed or recurrent BRCA-mutated/HRD ovarian cancer.

Large phase 3 studies have resulted in the approval of the antiangiogenic agent bevacizumab in combination with chemotherapy for the treatment of newly diagnosed and recurrent ovarian cancer, as well as for maintenance therapy at the conclusion of combination chemotherapy plus bevacizumab treatment of newly diagnosed (GOG 218 and ICON 7 trials) or recurrent ovarian cancer (GOG 218, OCEANS, and AURELIA trials). The most common toxicity with antiangiogenic agents is hypertension. Women also commonly experience arthralgia/myalgia. There is an increased risk of proteinuria, blood clots, bleeding, and serious gastrointestinal events such as fistula and bowel perforation.

Data from the phase 2 KEYNOTE 158 trial support pembrolizumab for microsatellite high or mismatch repair-deficient ovarian cancers. Common side effects associated with the use of pembrolizumab include fatigue, itchy skin, diarrhea, nausea, decreased appetite, rash, fever, cough, difficulty breathing, musculoskeletal pain, constipation, and joint pain. Pembrolizumab can cause the immune system to attack normal organs and tissues in the body resulting in serious side effects, including inflammation of such organs as the lungs, colon, liver, endocrine glands, and kidneys. 

Evidence for hormonal therapy (i.e., aromatase inhibitors like letrozole) for the treatment of newly diagnosed and recurrent low-grade serous/endometrioid epithelial ovarian cancer comes from largely retrospective cohort studies. A large phase 3 study, now enrolling, will examine if letrozole monotherapy/maintenance is non-inferior to intravenous paclitaxel/carboplatin and maintenance letrozole with respect to progression-free survival in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

Hormonal therapies are generally very well tolerated. Common side effects may include hot flashes, warmth or redness in the face or chest, headache, dizziness, weakness, bone pain, muscle or joint pain, swelling, weight gain, increased sweating, or increased cholesterol in the blood.

What other drugs are in development for ovarian cancer?

VEGF receptor tyrosine kinase inhibitors, such as cediranib, are in development. Anlotinib is another drug being investigated. It is a new multi-target tyrosine kinase inhibitor that targets VEGFR, PDGFR, and FGFR. Drugs targeting folate-alpha receptor, such as mirvetuximab, are under investigation, particularly for patients with high folate-alpha receptor membrane staining by immunohistochemistry. Drugs targeting cell cycle arrest, such as CDK4/6 inhibitors, are also being considered.

Can you provide some of the highlights of ovarian cancer research presented at this year’s American Society of Clinical Oncology meeting ?

My take is that we have gone from a monotonous landscape of platinum doublet chemotherapy to an exciting, diversified landscape over the past several years. All of this activity has driven median overall survival up from 3 years to 5 years and progression-free survival following first platinum sensitive recurrence to well beyond 6 months.

Since last year’s meeting, we have seen several new approvals, including niraparib for the treatment of BRCA mutated and HRD disease, as well as for first-line maintenance in all comers. In May, the FDA expanded the indication for olaparib to include its combination with bevacizumab as first-line maintenance for BRCA-mutated and HRD disease based on the results of PAOLA-1. With certainty, our treatment paradigms will continue to evolve in response to these and other new data.

At this year’s meeting, the SOLO-2 investigators revealed the first overall survival data for second-line PARP inhibitor maintenance, which is the first suggestion that PARP inhibitor maintenance improves overall survival.

We have a new understanding about the genetics of long-term responders to rucaparib on ARIEL-2.

We also understand how the role of secondary cytoreductive surgery and how nonchemotherapy options for the treatment of platinum sensitive relapse compare in terms of efficacy and toxicity (i.e., AVANOVA-2 and GY004 trials). We see again the importance of R0 cytoreduction when surgery is pursued. Achieving anything less than R0 cytoreduction for the treatment of first platinum sensitive recurrence may translate into shorter survival, compared with chemotherapy alone.

We are also becoming increasingly familiar with the limited therapeutic benefit of single-agent anti-PD-1/PD-L1, which is so different from our experience in mismatch repair-deficient endometrial cancer. In the small percentage of responders, there are some durable responses and a suggestion of particular efficacy among women with clear cell ovarian cancer.

What other recent findings in ovarian cancer research should oncologists be aware of?

Data supporting improved efficacy of a gastrointestinal-type chemotherapy regimen for mucinous epithelial ovarian cancers come from a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers.  

Identification of inactivating SMARCA4 mutations as the driver of small cell carcinoma of the ovary, hypercalcemic type, and the idea that CDK4/6 inhibitors could be effectively repurposed to treat this rare but highly aggressive type of ovarian cancer is also new and exciting.

Dr. Stone has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The treatment of ovarian cancer has evolved considerably in the last few years, with the approval of several PARP inhibitors, antiangiogenic agents, and other therapies for a multitude of indications. Additional treatments are likely to soon join this already diverse spectrum of available options, if their promising efficacy and safety continues to be borne out in ongoing research.

To better understand the individual merits and potential drawbacks of these treatments, Medscape recently spoke with Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, Baltimore. This interview has been edited for length and clarity.

Medscape: We’re starting to see preliminary data on pamiparib , an investigational inhibitor of PARP1 and PARP2, for the treatment of ovarian cancer. What is the evidence supporting this drug?

Dr. Stone: Currently, six different PARP inhibitors – olaparib, rucaparib, veliparib, niraparib, talazoparib, and pamiparib – have been in clinical development at different stages. In clinical applications, PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, have demonstrated sustained antitumor responses as single agents in patients with BRCA1 or BRCA2 mutations. Those with Food and Drug Administration indications in ovarian cancer include olaparib, rucaparib, and niraparib. The preclinical and clinical data with pamiparib is limited as of now. But, in a xenograft breast cancer model, it was found to be over 10 times more potent than olaparib.

If approved, where would pamiparib fit in the treatment paradigm for ovarian cancer?

It would potentially fit as monotherapy as well as in combination with agents other than standard chemotherapy for the treatment of BRCA mutated ovarian cancer. It could also be considered for maintenance therapy at the conclusion of chemotherapy treatment of newly diagnosed or recurrent BRCA-mutated ovarian cancer.

What adverse events are associated with pamiparib? How does the toxicity profile compare with other drugs for ovarian cancer?

With respect to PARP inhibitors, the differences in potency (PARP trapping) correlate with their toxicity profiles. The most common adverse events are gastrointestinal, hematologic, and constitutional (fatigue). Even though it is difficult to compare toxicities across different trials with heterogeneous patient populations, there are a few points worth noting.

Rucaparib leads to inhibition of renal transporter proteins involved in secretion of creatinine and can lead to increased creatinine (any grade: 15%; grade 3: ≤1%). Transaminitis is generally self-limiting and highest with rucaparib (any grade: 34%; grade 3: 10%). Hematologic toxicities are the highest with niraparib (any grade: thrombocytopenia 61%, anemia 50%, neutropenia 30%; grade ≥3: thrombocytopenia 34%, anemia 25%, neutropenia 20%).

Toxicities are more common in the first few cycles of treatment, warranting closer early monitoring. This differs somewhat from the gastrointestinal, hematological, and constitutional (fatigue) adverse events that we see with common chemotherapeutic agents used to treat ovarian cancer, which are generally cumulative.

PARP inhibitor treatment is also associated with an increased risk of developing myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). That being said, therapy-related MDS/AML is a well-recognized complication of conventional chemotherapy used to treat a variety of primary malignancies, including ovarian cancer.

The expected toxicity profile for pamiparib is based on what we have seen with the other PARP inhibitors. This includes any grade nausea (50%), fatigue (33%), anemia (20%), vomiting (15%), and neutropenia (13%). Toxicity of grade 3 or higher includes anemia (13%), neutropenia (8%), and fatigue (5%).

Where do the newest drugs to be approved for ovarian cancer in recent years fit within the treatment paradigm? What do the research findings show about their efficacy and safety?

Data from phase 2/3 trials support the use of PARP inhibitors as monotherapy as well as in combination with other agents (most commonly agents other than standard chemotherapy) for the treatment of BRCA mutated or otherwise homologous recombination-deficient (HRD) ovarian cancer. They can also be considered for maintenance therapy at the conclusion of treatment of newly diagnosed or recurrent BRCA-mutated/HRD ovarian cancer.

Large phase 3 studies have resulted in the approval of the antiangiogenic agent bevacizumab in combination with chemotherapy for the treatment of newly diagnosed and recurrent ovarian cancer, as well as for maintenance therapy at the conclusion of combination chemotherapy plus bevacizumab treatment of newly diagnosed (GOG 218 and ICON 7 trials) or recurrent ovarian cancer (GOG 218, OCEANS, and AURELIA trials). The most common toxicity with antiangiogenic agents is hypertension. Women also commonly experience arthralgia/myalgia. There is an increased risk of proteinuria, blood clots, bleeding, and serious gastrointestinal events such as fistula and bowel perforation.

Data from the phase 2 KEYNOTE 158 trial support pembrolizumab for microsatellite high or mismatch repair-deficient ovarian cancers. Common side effects associated with the use of pembrolizumab include fatigue, itchy skin, diarrhea, nausea, decreased appetite, rash, fever, cough, difficulty breathing, musculoskeletal pain, constipation, and joint pain. Pembrolizumab can cause the immune system to attack normal organs and tissues in the body resulting in serious side effects, including inflammation of such organs as the lungs, colon, liver, endocrine glands, and kidneys. 

Evidence for hormonal therapy (i.e., aromatase inhibitors like letrozole) for the treatment of newly diagnosed and recurrent low-grade serous/endometrioid epithelial ovarian cancer comes from largely retrospective cohort studies. A large phase 3 study, now enrolling, will examine if letrozole monotherapy/maintenance is non-inferior to intravenous paclitaxel/carboplatin and maintenance letrozole with respect to progression-free survival in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

Hormonal therapies are generally very well tolerated. Common side effects may include hot flashes, warmth or redness in the face or chest, headache, dizziness, weakness, bone pain, muscle or joint pain, swelling, weight gain, increased sweating, or increased cholesterol in the blood.

What other drugs are in development for ovarian cancer?

VEGF receptor tyrosine kinase inhibitors, such as cediranib, are in development. Anlotinib is another drug being investigated. It is a new multi-target tyrosine kinase inhibitor that targets VEGFR, PDGFR, and FGFR. Drugs targeting folate-alpha receptor, such as mirvetuximab, are under investigation, particularly for patients with high folate-alpha receptor membrane staining by immunohistochemistry. Drugs targeting cell cycle arrest, such as CDK4/6 inhibitors, are also being considered.

Can you provide some of the highlights of ovarian cancer research presented at this year’s American Society of Clinical Oncology meeting ?

My take is that we have gone from a monotonous landscape of platinum doublet chemotherapy to an exciting, diversified landscape over the past several years. All of this activity has driven median overall survival up from 3 years to 5 years and progression-free survival following first platinum sensitive recurrence to well beyond 6 months.

Since last year’s meeting, we have seen several new approvals, including niraparib for the treatment of BRCA mutated and HRD disease, as well as for first-line maintenance in all comers. In May, the FDA expanded the indication for olaparib to include its combination with bevacizumab as first-line maintenance for BRCA-mutated and HRD disease based on the results of PAOLA-1. With certainty, our treatment paradigms will continue to evolve in response to these and other new data.

At this year’s meeting, the SOLO-2 investigators revealed the first overall survival data for second-line PARP inhibitor maintenance, which is the first suggestion that PARP inhibitor maintenance improves overall survival.

We have a new understanding about the genetics of long-term responders to rucaparib on ARIEL-2.

We also understand how the role of secondary cytoreductive surgery and how nonchemotherapy options for the treatment of platinum sensitive relapse compare in terms of efficacy and toxicity (i.e., AVANOVA-2 and GY004 trials). We see again the importance of R0 cytoreduction when surgery is pursued. Achieving anything less than R0 cytoreduction for the treatment of first platinum sensitive recurrence may translate into shorter survival, compared with chemotherapy alone.

We are also becoming increasingly familiar with the limited therapeutic benefit of single-agent anti-PD-1/PD-L1, which is so different from our experience in mismatch repair-deficient endometrial cancer. In the small percentage of responders, there are some durable responses and a suggestion of particular efficacy among women with clear cell ovarian cancer.

What other recent findings in ovarian cancer research should oncologists be aware of?

Data supporting improved efficacy of a gastrointestinal-type chemotherapy regimen for mucinous epithelial ovarian cancers come from a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers.  

Identification of inactivating SMARCA4 mutations as the driver of small cell carcinoma of the ovary, hypercalcemic type, and the idea that CDK4/6 inhibitors could be effectively repurposed to treat this rare but highly aggressive type of ovarian cancer is also new and exciting.

Dr. Stone has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The treatment of ovarian cancer has evolved considerably in the last few years, with the approval of several PARP inhibitors, antiangiogenic agents, and other therapies for a multitude of indications. Additional treatments are likely to soon join this already diverse spectrum of available options, if their promising efficacy and safety continues to be borne out in ongoing research.

To better understand the individual merits and potential drawbacks of these treatments, Medscape recently spoke with Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University, Baltimore. This interview has been edited for length and clarity.

Medscape: We’re starting to see preliminary data on pamiparib , an investigational inhibitor of PARP1 and PARP2, for the treatment of ovarian cancer. What is the evidence supporting this drug?

Dr. Stone: Currently, six different PARP inhibitors – olaparib, rucaparib, veliparib, niraparib, talazoparib, and pamiparib – have been in clinical development at different stages. In clinical applications, PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, have demonstrated sustained antitumor responses as single agents in patients with BRCA1 or BRCA2 mutations. Those with Food and Drug Administration indications in ovarian cancer include olaparib, rucaparib, and niraparib. The preclinical and clinical data with pamiparib is limited as of now. But, in a xenograft breast cancer model, it was found to be over 10 times more potent than olaparib.

If approved, where would pamiparib fit in the treatment paradigm for ovarian cancer?

It would potentially fit as monotherapy as well as in combination with agents other than standard chemotherapy for the treatment of BRCA mutated ovarian cancer. It could also be considered for maintenance therapy at the conclusion of chemotherapy treatment of newly diagnosed or recurrent BRCA-mutated ovarian cancer.

What adverse events are associated with pamiparib? How does the toxicity profile compare with other drugs for ovarian cancer?

With respect to PARP inhibitors, the differences in potency (PARP trapping) correlate with their toxicity profiles. The most common adverse events are gastrointestinal, hematologic, and constitutional (fatigue). Even though it is difficult to compare toxicities across different trials with heterogeneous patient populations, there are a few points worth noting.

Rucaparib leads to inhibition of renal transporter proteins involved in secretion of creatinine and can lead to increased creatinine (any grade: 15%; grade 3: ≤1%). Transaminitis is generally self-limiting and highest with rucaparib (any grade: 34%; grade 3: 10%). Hematologic toxicities are the highest with niraparib (any grade: thrombocytopenia 61%, anemia 50%, neutropenia 30%; grade ≥3: thrombocytopenia 34%, anemia 25%, neutropenia 20%).

Toxicities are more common in the first few cycles of treatment, warranting closer early monitoring. This differs somewhat from the gastrointestinal, hematological, and constitutional (fatigue) adverse events that we see with common chemotherapeutic agents used to treat ovarian cancer, which are generally cumulative.

PARP inhibitor treatment is also associated with an increased risk of developing myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). That being said, therapy-related MDS/AML is a well-recognized complication of conventional chemotherapy used to treat a variety of primary malignancies, including ovarian cancer.

The expected toxicity profile for pamiparib is based on what we have seen with the other PARP inhibitors. This includes any grade nausea (50%), fatigue (33%), anemia (20%), vomiting (15%), and neutropenia (13%). Toxicity of grade 3 or higher includes anemia (13%), neutropenia (8%), and fatigue (5%).

Where do the newest drugs to be approved for ovarian cancer in recent years fit within the treatment paradigm? What do the research findings show about their efficacy and safety?

Data from phase 2/3 trials support the use of PARP inhibitors as monotherapy as well as in combination with other agents (most commonly agents other than standard chemotherapy) for the treatment of BRCA mutated or otherwise homologous recombination-deficient (HRD) ovarian cancer. They can also be considered for maintenance therapy at the conclusion of treatment of newly diagnosed or recurrent BRCA-mutated/HRD ovarian cancer.

Large phase 3 studies have resulted in the approval of the antiangiogenic agent bevacizumab in combination with chemotherapy for the treatment of newly diagnosed and recurrent ovarian cancer, as well as for maintenance therapy at the conclusion of combination chemotherapy plus bevacizumab treatment of newly diagnosed (GOG 218 and ICON 7 trials) or recurrent ovarian cancer (GOG 218, OCEANS, and AURELIA trials). The most common toxicity with antiangiogenic agents is hypertension. Women also commonly experience arthralgia/myalgia. There is an increased risk of proteinuria, blood clots, bleeding, and serious gastrointestinal events such as fistula and bowel perforation.

Data from the phase 2 KEYNOTE 158 trial support pembrolizumab for microsatellite high or mismatch repair-deficient ovarian cancers. Common side effects associated with the use of pembrolizumab include fatigue, itchy skin, diarrhea, nausea, decreased appetite, rash, fever, cough, difficulty breathing, musculoskeletal pain, constipation, and joint pain. Pembrolizumab can cause the immune system to attack normal organs and tissues in the body resulting in serious side effects, including inflammation of such organs as the lungs, colon, liver, endocrine glands, and kidneys. 

Evidence for hormonal therapy (i.e., aromatase inhibitors like letrozole) for the treatment of newly diagnosed and recurrent low-grade serous/endometrioid epithelial ovarian cancer comes from largely retrospective cohort studies. A large phase 3 study, now enrolling, will examine if letrozole monotherapy/maintenance is non-inferior to intravenous paclitaxel/carboplatin and maintenance letrozole with respect to progression-free survival in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

Hormonal therapies are generally very well tolerated. Common side effects may include hot flashes, warmth or redness in the face or chest, headache, dizziness, weakness, bone pain, muscle or joint pain, swelling, weight gain, increased sweating, or increased cholesterol in the blood.

What other drugs are in development for ovarian cancer?

VEGF receptor tyrosine kinase inhibitors, such as cediranib, are in development. Anlotinib is another drug being investigated. It is a new multi-target tyrosine kinase inhibitor that targets VEGFR, PDGFR, and FGFR. Drugs targeting folate-alpha receptor, such as mirvetuximab, are under investigation, particularly for patients with high folate-alpha receptor membrane staining by immunohistochemistry. Drugs targeting cell cycle arrest, such as CDK4/6 inhibitors, are also being considered.

Can you provide some of the highlights of ovarian cancer research presented at this year’s American Society of Clinical Oncology meeting ?

My take is that we have gone from a monotonous landscape of platinum doublet chemotherapy to an exciting, diversified landscape over the past several years. All of this activity has driven median overall survival up from 3 years to 5 years and progression-free survival following first platinum sensitive recurrence to well beyond 6 months.

Since last year’s meeting, we have seen several new approvals, including niraparib for the treatment of BRCA mutated and HRD disease, as well as for first-line maintenance in all comers. In May, the FDA expanded the indication for olaparib to include its combination with bevacizumab as first-line maintenance for BRCA-mutated and HRD disease based on the results of PAOLA-1. With certainty, our treatment paradigms will continue to evolve in response to these and other new data.

At this year’s meeting, the SOLO-2 investigators revealed the first overall survival data for second-line PARP inhibitor maintenance, which is the first suggestion that PARP inhibitor maintenance improves overall survival.

We have a new understanding about the genetics of long-term responders to rucaparib on ARIEL-2.

We also understand how the role of secondary cytoreductive surgery and how nonchemotherapy options for the treatment of platinum sensitive relapse compare in terms of efficacy and toxicity (i.e., AVANOVA-2 and GY004 trials). We see again the importance of R0 cytoreduction when surgery is pursued. Achieving anything less than R0 cytoreduction for the treatment of first platinum sensitive recurrence may translate into shorter survival, compared with chemotherapy alone.

We are also becoming increasingly familiar with the limited therapeutic benefit of single-agent anti-PD-1/PD-L1, which is so different from our experience in mismatch repair-deficient endometrial cancer. In the small percentage of responders, there are some durable responses and a suggestion of particular efficacy among women with clear cell ovarian cancer.

What other recent findings in ovarian cancer research should oncologists be aware of?

Data supporting improved efficacy of a gastrointestinal-type chemotherapy regimen for mucinous epithelial ovarian cancers come from a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers.  

Identification of inactivating SMARCA4 mutations as the driver of small cell carcinoma of the ovary, hypercalcemic type, and the idea that CDK4/6 inhibitors could be effectively repurposed to treat this rare but highly aggressive type of ovarian cancer is also new and exciting.

Dr. Stone has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Issues with the MOC

In Dr. Nasrallah’s editorial “Revamp the MOC” (From the Editor, Current Psychiatry. September 2020, p. 7-10), he addresses the American Board of Psychiatry and Neurology (ABPN) Maintenance of Certification (MOC) program, which—in my opinion—is nothing more than a folly and a greedy money grab designed to extort revenue from practicing psychiatrists. Like Dr. Nasrallah, my initial board certification consisted of a written exam, followed by a face-to-face oral exam. Most candidates, myself included, did not relish the thought of being subjected to the scrutiny of an oral exam. It was truly an anxiety-provoking and nerve-wracking ordeal, but in the end, the exam revealed itself to be an amazingly effective and legitimate measuring stick.

I was not so fortunate to have been grandfathered with lifetime certification, so I have been forced to recertify twice now. I will be 70 years old when I will need to decide whether to recertify once again. It is my belief that the MOC process is cumbersome and nonsensical, having little, if any, relevance in assessing one’s competency. Again, the ABPN’s purpose is not to “protect the public” and ensure safe and competent care, but to generate tremendous revenue for the Board. How can any rational individual believe that this exam is a legitimate test of one’s knowledge and competency when the pass rates are so stratospherically high year after year? I do not know of a single individual who has failed the recertification exam, so it would appear that if you pay the fees and sit for the exam, you will pass. It saddens me that the Board can perpetrate such a hoax on the public, leading them to believe that the MOC actually means something.

The cost to recertify is not inexpensive. Apparently, in a desire to add to its coffers, the ABPN has recently implemented the Physician Folios portal, whereby psychiatrists are forced to pay an annual fee. Its purpose, according to the Board, is to provide“a dynamic conduit for important data exchange such as making updates to personal contact information, updating medical license information, and applying and paying for an examination.”¹ Give me a break!

It is my hope that a better, less expensive, more appropriate system is developed, allowing the psychiatrist to focus his/her efforts on treating patients.

Terrence Boyadjis, MD
Private psychiatric practice
West Chester, Pennsylvania

Reference
1. American Board of Psychiatry and Neurology. ABPN Physician Folios. https://application.abpn.com/webclient/landing_page.asp. Accessed October 20, 2020.

Dr. Nasrallah’s editorial about the MOC process is another addition to his collection of many of the best editorials I’ve ever read. I related fondly to his experiences taking the oral exam, which I took in 1972. I also became an examiner during the mid-1970s. Dr. Nasrallah continues to be a source of down-to-earth wisdom for our beloved profession.

Richard W. Worst, MD
Twin Falls, Idaho

Continue to: Overcoming a ‘quadruple threat’

Dr. Nasrallah’s editorial “Enduring the ordeal of a quadruple threat is especially arduous for psychiatric patients” (From the Editor, Current Psychiatry. August 2020, p. 14,16,37) was very well written and most timely. Perhaps in seeking to help those who suffer from the “quadruple threat,” we may find solace for our own suffering. We are healers, and Dr. Nasrallah set our targets with grace and fervor.

Robert W. Pollack, MD
Founder/COO
Psychiatric Associates of Southwest Florida 
Fort Myers, Florida

Disclosures: The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Issues with the MOC

In Dr. Nasrallah’s editorial “Revamp the MOC” (From the Editor, Current Psychiatry. September 2020, p. 7-10), he addresses the American Board of Psychiatry and Neurology (ABPN) Maintenance of Certification (MOC) program, which—in my opinion—is nothing more than a folly and a greedy money grab designed to extort revenue from practicing psychiatrists. Like Dr. Nasrallah, my initial board certification consisted of a written exam, followed by a face-to-face oral exam. Most candidates, myself included, did not relish the thought of being subjected to the scrutiny of an oral exam. It was truly an anxiety-provoking and nerve-wracking ordeal, but in the end, the exam revealed itself to be an amazingly effective and legitimate measuring stick.

I was not so fortunate to have been grandfathered with lifetime certification, so I have been forced to recertify twice now. I will be 70 years old when I will need to decide whether to recertify once again. It is my belief that the MOC process is cumbersome and nonsensical, having little, if any, relevance in assessing one’s competency. Again, the ABPN’s purpose is not to “protect the public” and ensure safe and competent care, but to generate tremendous revenue for the Board. How can any rational individual believe that this exam is a legitimate test of one’s knowledge and competency when the pass rates are so stratospherically high year after year? I do not know of a single individual who has failed the recertification exam, so it would appear that if you pay the fees and sit for the exam, you will pass. It saddens me that the Board can perpetrate such a hoax on the public, leading them to believe that the MOC actually means something.

The cost to recertify is not inexpensive. Apparently, in a desire to add to its coffers, the ABPN has recently implemented the Physician Folios portal, whereby psychiatrists are forced to pay an annual fee. Its purpose, according to the Board, is to provide“a dynamic conduit for important data exchange such as making updates to personal contact information, updating medical license information, and applying and paying for an examination.”¹ Give me a break!

It is my hope that a better, less expensive, more appropriate system is developed, allowing the psychiatrist to focus his/her efforts on treating patients.

Terrence Boyadjis, MD
Private psychiatric practice
West Chester, Pennsylvania

Reference
1. American Board of Psychiatry and Neurology. ABPN Physician Folios. https://application.abpn.com/webclient/landing_page.asp. Accessed October 20, 2020.

Dr. Nasrallah’s editorial about the MOC process is another addition to his collection of many of the best editorials I’ve ever read. I related fondly to his experiences taking the oral exam, which I took in 1972. I also became an examiner during the mid-1970s. Dr. Nasrallah continues to be a source of down-to-earth wisdom for our beloved profession.

Richard W. Worst, MD
Twin Falls, Idaho

Continue to: Overcoming a ‘quadruple threat’

Dr. Nasrallah’s editorial “Enduring the ordeal of a quadruple threat is especially arduous for psychiatric patients” (From the Editor, Current Psychiatry. August 2020, p. 14,16,37) was very well written and most timely. Perhaps in seeking to help those who suffer from the “quadruple threat,” we may find solace for our own suffering. We are healers, and Dr. Nasrallah set our targets with grace and fervor.

Robert W. Pollack, MD
Founder/COO
Psychiatric Associates of Southwest Florida 
Fort Myers, Florida

Disclosures: The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Issues with the MOC

In Dr. Nasrallah’s editorial “Revamp the MOC” (From the Editor, Current Psychiatry. September 2020, p. 7-10), he addresses the American Board of Psychiatry and Neurology (ABPN) Maintenance of Certification (MOC) program, which—in my opinion—is nothing more than a folly and a greedy money grab designed to extort revenue from practicing psychiatrists. Like Dr. Nasrallah, my initial board certification consisted of a written exam, followed by a face-to-face oral exam. Most candidates, myself included, did not relish the thought of being subjected to the scrutiny of an oral exam. It was truly an anxiety-provoking and nerve-wracking ordeal, but in the end, the exam revealed itself to be an amazingly effective and legitimate measuring stick.

I was not so fortunate to have been grandfathered with lifetime certification, so I have been forced to recertify twice now. I will be 70 years old when I will need to decide whether to recertify once again. It is my belief that the MOC process is cumbersome and nonsensical, having little, if any, relevance in assessing one’s competency. Again, the ABPN’s purpose is not to “protect the public” and ensure safe and competent care, but to generate tremendous revenue for the Board. How can any rational individual believe that this exam is a legitimate test of one’s knowledge and competency when the pass rates are so stratospherically high year after year? I do not know of a single individual who has failed the recertification exam, so it would appear that if you pay the fees and sit for the exam, you will pass. It saddens me that the Board can perpetrate such a hoax on the public, leading them to believe that the MOC actually means something.

The cost to recertify is not inexpensive. Apparently, in a desire to add to its coffers, the ABPN has recently implemented the Physician Folios portal, whereby psychiatrists are forced to pay an annual fee. Its purpose, according to the Board, is to provide“a dynamic conduit for important data exchange such as making updates to personal contact information, updating medical license information, and applying and paying for an examination.”¹ Give me a break!

It is my hope that a better, less expensive, more appropriate system is developed, allowing the psychiatrist to focus his/her efforts on treating patients.

Terrence Boyadjis, MD
Private psychiatric practice
West Chester, Pennsylvania

Reference
1. American Board of Psychiatry and Neurology. ABPN Physician Folios. https://application.abpn.com/webclient/landing_page.asp. Accessed October 20, 2020.

Dr. Nasrallah’s editorial about the MOC process is another addition to his collection of many of the best editorials I’ve ever read. I related fondly to his experiences taking the oral exam, which I took in 1972. I also became an examiner during the mid-1970s. Dr. Nasrallah continues to be a source of down-to-earth wisdom for our beloved profession.

Richard W. Worst, MD
Twin Falls, Idaho

Continue to: Overcoming a ‘quadruple threat’

Dr. Nasrallah’s editorial “Enduring the ordeal of a quadruple threat is especially arduous for psychiatric patients” (From the Editor, Current Psychiatry. August 2020, p. 14,16,37) was very well written and most timely. Perhaps in seeking to help those who suffer from the “quadruple threat,” we may find solace for our own suffering. We are healers, and Dr. Nasrallah set our targets with grace and fervor.

Robert W. Pollack, MD
Founder/COO
Psychiatric Associates of Southwest Florida 
Fort Myers, Florida

Disclosures: The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.

Let’s face it: The greatest unmet need in psychiatry is discovering a treatment for the infamous syndrome of toxic political extremism. Its ugly symptoms include blind hatred, visceral malice, bigotry, vandalism, hypocrisy, racism, hubris, intransigence, narcissism, demagoguery, mutual contempt, and intense schadenfreude.

This corrosive affliction has engulfed and polluted our society, and compromised our well-being and quality of life. Treating this malignant syndrome is beyond the reach of psychopharmacology!

Thus, we psychiatrists should focus on the mood, psychotic, anxiety, and addiction syndromes that we encounter daily in our hospitals, clinics, and private offices. They affect tens of millions of patients. We currently have many psychotropic medications for these conditions. When combined with psychotherapy, the resulting synergy can be magical and immensely gratifying. However, some of those agents have limited efficacy due to the extensive heterogeneity of syndromes such as schizophrenia or depression, which are often confounded with comorbidities. A perfect balance between efficacy, tolerability, and safety are often hard to come by in pharmacotherapy.

The most glaring psychopharmacologic unmet need is that 80% of DSM disorders still do not have a single FDA-approved (evidence-based) medication.¹ It will take decades, hundreds of billions of dollars, and the motivation of the often-maligned pharmaceutical industry (indispensable, because they are the only entity with the large R&D infrastructure to develop medications for psychiatry). Both academic and clinical psychiatrists must advise pharmaceutical companies about the unmet needs in our field and urge them to develop novel pharmacotherapies to address the gaps in the clinical care of psychiatric patients.

An inventory of unmet needs

With that in mind, here is a list of unmet needs I have been thinking about lately, and hoping that they will be resolved to help our patients achieve better clinical and functional outcomes.

Rapid-onset antipsychotics. The discovery that ketamine can rapidly convert refractory patients who are chronically depressed or suicidal to normal mood within a few hours shattered the dogma that weeks and months are needed for severe depression to improve, let alone achieve full remission. There is a similar dogma about psychosis requiring a protracted duration of antipsychotic treatment to attain significant impact. A rapid-acting antipsychotic agent would represent a major advance in psychiatry and its pharmaco-economic benefits would be substantial, given the high cost of inpatient hospitalization. Just as neurobiologic research guided the discovery of ketamine as a dramatic paradigm shift in treating depression, targeted research, especially focusing on glutamate pathways, may help identify a rapid-onset agent, whether oral, intranasal, IV, or even (why not) intrathecal. Research is known to enhance serendipity, which has been kind to psychiatry and has led to the discovery of several pharmacologic therapies in psychiatry, such as chlorpromazine, monoamine oxidase inhibitor antidepressants, and lithium.

Long-acting antidepressants and anxiolytics. This can be regarded as low-hanging fruit. Several technologies have been developed for long-acting formulations, yet they have been exploited mainly for antipsychotic medications. Some of these technologies can be employed to convert commonly used antidepressants (such as selective serotonin reuptake inhibitors) into long-acting antidepressants that can also reduce anxiety. Nonadherence among patients with depression is quite common, and relapses may lead to suicide attempts. The use of injectable, long-acting antidepressants can also reduce the incidence of overdoses because the patient will not have possession of potentially fatal pills.

Continue to: Long-acting mood stabilizers

Long-acting mood stabilizers. The rationale for long-acting mood stabilizers is the same as for long-acting antidepressants. Patients with bipolar disorder are known to stop taking their medications because they miss their “highs.” Some long-acting antipsychotics are approved for bipolar disorder, but these are often associated with adverse effects, such as metabolic dysregulation, extrapyramidal symptoms, and tardive dyskinesia. Mood stabilizers are essential for the bipolar spectrum.

A “real” treatment for alcohol use disorders that eliminates craving for alcohol. Alcoholism is associated with more than 100 medical complications and is one of the leading causes of disability in the world. It is frustrating that very few drug companies have focused on this widely prevalent brain disorder, which is also a common comorbid condition in many psychiatric syndromes.

Treatment-resistance pharmacotherapy solutions. All psychiatric syndromes are heterogeneous and contain ≥1 subgroups (biotypes) that fail to respond to what is considered the “standard” psychopharmacologic treatment (such as antipsychotics, antidepressants, mood stabilizers, or anti-obsessive medications). Technically, those so-called treatment-resistant subtypes need medications with a different mechanism of action. For example, clozapine for treatment-resistant schizophrenia and ketamine for treatment-resistant depression provide proof that treatment resistance is treatable but by a mechanism of action that is completely different from that of standard therapies, such as N-methyl-D-aspartate (NMDA) receptor modulation. And there is a need for more than one pharmacotherapy for treatment resistance because some patients do not respond to either clozapine or ketamine.

Negative symptoms of schizophrenia cause significant functional disability and are well known to be a major unmet need. Some promising data are emerging on agents such as pimavanserin, cariprazine, and roluperidone, which is encouraging, but nothing is approved yet.

Cognitive deficits of schizophrenia, both neurocognition and social cognition, are another major unmet need that impair function in many patients. Many attempts to develop a pharmacologic treatment for these serious cognitive impairments have been made, but several candidates that initially appeared promising have bitten the dust. A focus on modulating the glutamate NMDA receptor may eventually lead to a breakthrough, and that may also help patients with bipolar disorder and major depressive disorder, both of whom also have cognitive deficits in several domains, albeit less severe than those experienced by patients with schizophrenia.

Continue to: Personality disorders

Personality disorders, especially borderline personality disorder, are very challenging to treat pharmacologically despite their prevalence and serious disruption to people’s lives. Hardly any FDA clinical trials have been conducted on any personality disorder. It is an unmet need that all psychiatrists would love to see addressed. But the mythical notion that personality disorders are untreatable may be an impediment in the pursuit of novel pharmacotherapy for borderline, narcissistic, antisocial, or schizotypal personality disorders, and other disorders. Heart attacks and religious conversion often change the baseline personality dramatically.

Childhood disorders. Apart from attention-deficit/hyperactivity disorder (ADHD), very few childhood psychiatric disorders have an FDA-approved medication. Why do drug companies avoid conducting controlled clinical trials in children age <10 who have autism, spectrum disorders, conduct disorder, oppositional defiant disorder, and other disorders? Effective pharmacotherapy for these children can be regarded as a desirable early intervention that may short-circuit their progression to serious adult psychopathology.

Parsimonious psychopharmacology for the treatment of trans-diagnostic psychiatric disorders. Recent research strongly suggests there is a strong overlap among psychiatric conditions, genetically, clinically, and biologically.^2,3 For example, bipolar disorder is frequently accompanied by anxiety or substance use, patients with schizophrenia often experience anxiety, depression, or substance use, and ADHD has been found to share genes with autism.^4,5

Eating disorders. There are no truly efficacious pharmacologic treatments for anorexia or bulimia nervosa. Research in this area is thin, and needs to be beefed up.

Sexual disorders. A huge unmet need exists for the pharmacotherapy of many sexual disorders that can have serious legal consequences (paraphilias) or quality-of-life repercussions (low sexual desire and orgasm disorders).

Continue to: A coordinated effort

A coordinated effort

It will take a massive collaboration among multiple stakeholders to launch the herculean process of addressing the unmet needs of all the above psychiatric disorders. This includes:

• the pharmaceutical industry (to provide the massive financial investment and R&D expertise)
• the federal government (to provide incentives)
• the FDA (to allow novel clinical trial designs)
• academic psychiatrists (to conduct research to discover the pathophysiology of psychiatric diseases)
• clinical psychiatrists (to provide consultations and advise about the clinical gaps in current psychopharmacological treatments)
• psychiatric patients (who are needed to volunteer for large-scale clinical trials).

This will be a veritable “psychiatric Manhattan Project” to advance the treatment of numerous psychiatric illnesses. The greatest benefit of discovering cures for disabling mental disorders is the evaporation of the virulent stigma that continues to plague our patients.

As for the political extremism that has corroded our society, it may be beyond pharmacologic redemption. An antidote to the “kool aid” has not yet been invented…

Let’s face it: The greatest unmet need in psychiatry is discovering a treatment for the infamous syndrome of toxic political extremism. Its ugly symptoms include blind hatred, visceral malice, bigotry, vandalism, hypocrisy, racism, hubris, intransigence, narcissism, demagoguery, mutual contempt, and intense schadenfreude.

This corrosive affliction has engulfed and polluted our society, and compromised our well-being and quality of life. Treating this malignant syndrome is beyond the reach of psychopharmacology!

Thus, we psychiatrists should focus on the mood, psychotic, anxiety, and addiction syndromes that we encounter daily in our hospitals, clinics, and private offices. They affect tens of millions of patients. We currently have many psychotropic medications for these conditions. When combined with psychotherapy, the resulting synergy can be magical and immensely gratifying. However, some of those agents have limited efficacy due to the extensive heterogeneity of syndromes such as schizophrenia or depression, which are often confounded with comorbidities. A perfect balance between efficacy, tolerability, and safety are often hard to come by in pharmacotherapy.

The most glaring psychopharmacologic unmet need is that 80% of DSM disorders still do not have a single FDA-approved (evidence-based) medication.¹ It will take decades, hundreds of billions of dollars, and the motivation of the often-maligned pharmaceutical industry (indispensable, because they are the only entity with the large R&D infrastructure to develop medications for psychiatry). Both academic and clinical psychiatrists must advise pharmaceutical companies about the unmet needs in our field and urge them to develop novel pharmacotherapies to address the gaps in the clinical care of psychiatric patients.

An inventory of unmet needs

With that in mind, here is a list of unmet needs I have been thinking about lately, and hoping that they will be resolved to help our patients achieve better clinical and functional outcomes.

Rapid-onset antipsychotics. The discovery that ketamine can rapidly convert refractory patients who are chronically depressed or suicidal to normal mood within a few hours shattered the dogma that weeks and months are needed for severe depression to improve, let alone achieve full remission. There is a similar dogma about psychosis requiring a protracted duration of antipsychotic treatment to attain significant impact. A rapid-acting antipsychotic agent would represent a major advance in psychiatry and its pharmaco-economic benefits would be substantial, given the high cost of inpatient hospitalization. Just as neurobiologic research guided the discovery of ketamine as a dramatic paradigm shift in treating depression, targeted research, especially focusing on glutamate pathways, may help identify a rapid-onset agent, whether oral, intranasal, IV, or even (why not) intrathecal. Research is known to enhance serendipity, which has been kind to psychiatry and has led to the discovery of several pharmacologic therapies in psychiatry, such as chlorpromazine, monoamine oxidase inhibitor antidepressants, and lithium.

Long-acting antidepressants and anxiolytics. This can be regarded as low-hanging fruit. Several technologies have been developed for long-acting formulations, yet they have been exploited mainly for antipsychotic medications. Some of these technologies can be employed to convert commonly used antidepressants (such as selective serotonin reuptake inhibitors) into long-acting antidepressants that can also reduce anxiety. Nonadherence among patients with depression is quite common, and relapses may lead to suicide attempts. The use of injectable, long-acting antidepressants can also reduce the incidence of overdoses because the patient will not have possession of potentially fatal pills.

Continue to: Long-acting mood stabilizers

Long-acting mood stabilizers. The rationale for long-acting mood stabilizers is the same as for long-acting antidepressants. Patients with bipolar disorder are known to stop taking their medications because they miss their “highs.” Some long-acting antipsychotics are approved for bipolar disorder, but these are often associated with adverse effects, such as metabolic dysregulation, extrapyramidal symptoms, and tardive dyskinesia. Mood stabilizers are essential for the bipolar spectrum.

A “real” treatment for alcohol use disorders that eliminates craving for alcohol. Alcoholism is associated with more than 100 medical complications and is one of the leading causes of disability in the world. It is frustrating that very few drug companies have focused on this widely prevalent brain disorder, which is also a common comorbid condition in many psychiatric syndromes.

Treatment-resistance pharmacotherapy solutions. All psychiatric syndromes are heterogeneous and contain ≥1 subgroups (biotypes) that fail to respond to what is considered the “standard” psychopharmacologic treatment (such as antipsychotics, antidepressants, mood stabilizers, or anti-obsessive medications). Technically, those so-called treatment-resistant subtypes need medications with a different mechanism of action. For example, clozapine for treatment-resistant schizophrenia and ketamine for treatment-resistant depression provide proof that treatment resistance is treatable but by a mechanism of action that is completely different from that of standard therapies, such as N-methyl-D-aspartate (NMDA) receptor modulation. And there is a need for more than one pharmacotherapy for treatment resistance because some patients do not respond to either clozapine or ketamine.

Negative symptoms of schizophrenia cause significant functional disability and are well known to be a major unmet need. Some promising data are emerging on agents such as pimavanserin, cariprazine, and roluperidone, which is encouraging, but nothing is approved yet.

Cognitive deficits of schizophrenia, both neurocognition and social cognition, are another major unmet need that impair function in many patients. Many attempts to develop a pharmacologic treatment for these serious cognitive impairments have been made, but several candidates that initially appeared promising have bitten the dust. A focus on modulating the glutamate NMDA receptor may eventually lead to a breakthrough, and that may also help patients with bipolar disorder and major depressive disorder, both of whom also have cognitive deficits in several domains, albeit less severe than those experienced by patients with schizophrenia.

Continue to: Personality disorders

Personality disorders, especially borderline personality disorder, are very challenging to treat pharmacologically despite their prevalence and serious disruption to people’s lives. Hardly any FDA clinical trials have been conducted on any personality disorder. It is an unmet need that all psychiatrists would love to see addressed. But the mythical notion that personality disorders are untreatable may be an impediment in the pursuit of novel pharmacotherapy for borderline, narcissistic, antisocial, or schizotypal personality disorders, and other disorders. Heart attacks and religious conversion often change the baseline personality dramatically.

Childhood disorders. Apart from attention-deficit/hyperactivity disorder (ADHD), very few childhood psychiatric disorders have an FDA-approved medication. Why do drug companies avoid conducting controlled clinical trials in children age <10 who have autism, spectrum disorders, conduct disorder, oppositional defiant disorder, and other disorders? Effective pharmacotherapy for these children can be regarded as a desirable early intervention that may short-circuit their progression to serious adult psychopathology.

Parsimonious psychopharmacology for the treatment of trans-diagnostic psychiatric disorders. Recent research strongly suggests there is a strong overlap among psychiatric conditions, genetically, clinically, and biologically.^2,3 For example, bipolar disorder is frequently accompanied by anxiety or substance use, patients with schizophrenia often experience anxiety, depression, or substance use, and ADHD has been found to share genes with autism.^4,5

Eating disorders. There are no truly efficacious pharmacologic treatments for anorexia or bulimia nervosa. Research in this area is thin, and needs to be beefed up.

Sexual disorders. A huge unmet need exists for the pharmacotherapy of many sexual disorders that can have serious legal consequences (paraphilias) or quality-of-life repercussions (low sexual desire and orgasm disorders).

Continue to: A coordinated effort

A coordinated effort

It will take a massive collaboration among multiple stakeholders to launch the herculean process of addressing the unmet needs of all the above psychiatric disorders. This includes:

• the pharmaceutical industry (to provide the massive financial investment and R&D expertise)
• the federal government (to provide incentives)
• the FDA (to allow novel clinical trial designs)
• academic psychiatrists (to conduct research to discover the pathophysiology of psychiatric diseases)
• clinical psychiatrists (to provide consultations and advise about the clinical gaps in current psychopharmacological treatments)
• psychiatric patients (who are needed to volunteer for large-scale clinical trials).

This will be a veritable “psychiatric Manhattan Project” to advance the treatment of numerous psychiatric illnesses. The greatest benefit of discovering cures for disabling mental disorders is the evaporation of the virulent stigma that continues to plague our patients.

As for the political extremism that has corroded our society, it may be beyond pharmacologic redemption. An antidote to the “kool aid” has not yet been invented…

Let’s face it: The greatest unmet need in psychiatry is discovering a treatment for the infamous syndrome of toxic political extremism. Its ugly symptoms include blind hatred, visceral malice, bigotry, vandalism, hypocrisy, racism, hubris, intransigence, narcissism, demagoguery, mutual contempt, and intense schadenfreude.

This corrosive affliction has engulfed and polluted our society, and compromised our well-being and quality of life. Treating this malignant syndrome is beyond the reach of psychopharmacology!

Thus, we psychiatrists should focus on the mood, psychotic, anxiety, and addiction syndromes that we encounter daily in our hospitals, clinics, and private offices. They affect tens of millions of patients. We currently have many psychotropic medications for these conditions. When combined with psychotherapy, the resulting synergy can be magical and immensely gratifying. However, some of those agents have limited efficacy due to the extensive heterogeneity of syndromes such as schizophrenia or depression, which are often confounded with comorbidities. A perfect balance between efficacy, tolerability, and safety are often hard to come by in pharmacotherapy.

The most glaring psychopharmacologic unmet need is that 80% of DSM disorders still do not have a single FDA-approved (evidence-based) medication.¹ It will take decades, hundreds of billions of dollars, and the motivation of the often-maligned pharmaceutical industry (indispensable, because they are the only entity with the large R&D infrastructure to develop medications for psychiatry). Both academic and clinical psychiatrists must advise pharmaceutical companies about the unmet needs in our field and urge them to develop novel pharmacotherapies to address the gaps in the clinical care of psychiatric patients.

An inventory of unmet needs

With that in mind, here is a list of unmet needs I have been thinking about lately, and hoping that they will be resolved to help our patients achieve better clinical and functional outcomes.

Rapid-onset antipsychotics. The discovery that ketamine can rapidly convert refractory patients who are chronically depressed or suicidal to normal mood within a few hours shattered the dogma that weeks and months are needed for severe depression to improve, let alone achieve full remission. There is a similar dogma about psychosis requiring a protracted duration of antipsychotic treatment to attain significant impact. A rapid-acting antipsychotic agent would represent a major advance in psychiatry and its pharmaco-economic benefits would be substantial, given the high cost of inpatient hospitalization. Just as neurobiologic research guided the discovery of ketamine as a dramatic paradigm shift in treating depression, targeted research, especially focusing on glutamate pathways, may help identify a rapid-onset agent, whether oral, intranasal, IV, or even (why not) intrathecal. Research is known to enhance serendipity, which has been kind to psychiatry and has led to the discovery of several pharmacologic therapies in psychiatry, such as chlorpromazine, monoamine oxidase inhibitor antidepressants, and lithium.

Long-acting antidepressants and anxiolytics. This can be regarded as low-hanging fruit. Several technologies have been developed for long-acting formulations, yet they have been exploited mainly for antipsychotic medications. Some of these technologies can be employed to convert commonly used antidepressants (such as selective serotonin reuptake inhibitors) into long-acting antidepressants that can also reduce anxiety. Nonadherence among patients with depression is quite common, and relapses may lead to suicide attempts. The use of injectable, long-acting antidepressants can also reduce the incidence of overdoses because the patient will not have possession of potentially fatal pills.

Continue to: Long-acting mood stabilizers

Long-acting mood stabilizers. The rationale for long-acting mood stabilizers is the same as for long-acting antidepressants. Patients with bipolar disorder are known to stop taking their medications because they miss their “highs.” Some long-acting antipsychotics are approved for bipolar disorder, but these are often associated with adverse effects, such as metabolic dysregulation, extrapyramidal symptoms, and tardive dyskinesia. Mood stabilizers are essential for the bipolar spectrum.

A “real” treatment for alcohol use disorders that eliminates craving for alcohol. Alcoholism is associated with more than 100 medical complications and is one of the leading causes of disability in the world. It is frustrating that very few drug companies have focused on this widely prevalent brain disorder, which is also a common comorbid condition in many psychiatric syndromes.

Treatment-resistance pharmacotherapy solutions. All psychiatric syndromes are heterogeneous and contain ≥1 subgroups (biotypes) that fail to respond to what is considered the “standard” psychopharmacologic treatment (such as antipsychotics, antidepressants, mood stabilizers, or anti-obsessive medications). Technically, those so-called treatment-resistant subtypes need medications with a different mechanism of action. For example, clozapine for treatment-resistant schizophrenia and ketamine for treatment-resistant depression provide proof that treatment resistance is treatable but by a mechanism of action that is completely different from that of standard therapies, such as N-methyl-D-aspartate (NMDA) receptor modulation. And there is a need for more than one pharmacotherapy for treatment resistance because some patients do not respond to either clozapine or ketamine.

Negative symptoms of schizophrenia cause significant functional disability and are well known to be a major unmet need. Some promising data are emerging on agents such as pimavanserin, cariprazine, and roluperidone, which is encouraging, but nothing is approved yet.

Cognitive deficits of schizophrenia, both neurocognition and social cognition, are another major unmet need that impair function in many patients. Many attempts to develop a pharmacologic treatment for these serious cognitive impairments have been made, but several candidates that initially appeared promising have bitten the dust. A focus on modulating the glutamate NMDA receptor may eventually lead to a breakthrough, and that may also help patients with bipolar disorder and major depressive disorder, both of whom also have cognitive deficits in several domains, albeit less severe than those experienced by patients with schizophrenia.

Continue to: Personality disorders

Personality disorders, especially borderline personality disorder, are very challenging to treat pharmacologically despite their prevalence and serious disruption to people’s lives. Hardly any FDA clinical trials have been conducted on any personality disorder. It is an unmet need that all psychiatrists would love to see addressed. But the mythical notion that personality disorders are untreatable may be an impediment in the pursuit of novel pharmacotherapy for borderline, narcissistic, antisocial, or schizotypal personality disorders, and other disorders. Heart attacks and religious conversion often change the baseline personality dramatically.

Childhood disorders. Apart from attention-deficit/hyperactivity disorder (ADHD), very few childhood psychiatric disorders have an FDA-approved medication. Why do drug companies avoid conducting controlled clinical trials in children age <10 who have autism, spectrum disorders, conduct disorder, oppositional defiant disorder, and other disorders? Effective pharmacotherapy for these children can be regarded as a desirable early intervention that may short-circuit their progression to serious adult psychopathology.

Parsimonious psychopharmacology for the treatment of trans-diagnostic psychiatric disorders. Recent research strongly suggests there is a strong overlap among psychiatric conditions, genetically, clinically, and biologically.^2,3 For example, bipolar disorder is frequently accompanied by anxiety or substance use, patients with schizophrenia often experience anxiety, depression, or substance use, and ADHD has been found to share genes with autism.^4,5

Eating disorders. There are no truly efficacious pharmacologic treatments for anorexia or bulimia nervosa. Research in this area is thin, and needs to be beefed up.

Sexual disorders. A huge unmet need exists for the pharmacotherapy of many sexual disorders that can have serious legal consequences (paraphilias) or quality-of-life repercussions (low sexual desire and orgasm disorders).

Continue to: A coordinated effort

A coordinated effort

It will take a massive collaboration among multiple stakeholders to launch the herculean process of addressing the unmet needs of all the above psychiatric disorders. This includes:

• the pharmaceutical industry (to provide the massive financial investment and R&D expertise)
• the federal government (to provide incentives)
• the FDA (to allow novel clinical trial designs)
• academic psychiatrists (to conduct research to discover the pathophysiology of psychiatric diseases)
• clinical psychiatrists (to provide consultations and advise about the clinical gaps in current psychopharmacological treatments)
• psychiatric patients (who are needed to volunteer for large-scale clinical trials).

This will be a veritable “psychiatric Manhattan Project” to advance the treatment of numerous psychiatric illnesses. The greatest benefit of discovering cures for disabling mental disorders is the evaporation of the virulent stigma that continues to plague our patients.

As for the political extremism that has corroded our society, it may be beyond pharmacologic redemption. An antidote to the “kool aid” has not yet been invented…

A 53-year-old woman presents for evaluation of persistent abdominal pain over the past 6 months. She reports the pain is about a 7 out of 10, located in the right upper quadrant. The pain does not worsen with food and not relieved with bowel movements. She has no nausea or vomiting. She reports that the pain worsens when she is sitting or standing and is relieved by lying down. Her past medical history includes having had a cholecystectomy in 2016, having hypertension, and having type 2 diabetes mellitus.

The patient’s medications include metformin, lisinopril, and empagliflozin. Her blood pressure was 130/70, and her pulse was 80. An abdominal exam of her found tenderness to palpation in the right upper quadrant, and no rebound tenderness. Her labs found a white blood cell count of 5.4, a hematocrit of 44%, an erythrocyte sedimentation rate of 13, a C-reactive protein of 1.0, a bilirubin of .8, an alkaline phosphatase of 100, an aspartate aminotransferase of 30, and an alanine transaminase of 22.



What is the most appropriate next step?

A) Right side up oblique ultrasound.

B) Abdominal CT scan.

C) Upper endoscopy.

D) More detailed physical exam.



The correct answer here is D, a more detailed physical exam is needed. Given the positional nature of this patient’s abdominal pain, an evaluation for an abdominal wall cause is appropriate.

Abdominal wall pain as a cause of chronic abdominal pain is rarely considered, but it really should be. Costanza and colleagues looked at 2,709 patients referred to gastroenterologists for chronic abdominal pain.¹ Chronic abdominal wall pain was diagnosed in 137 patients, with the diagnosis unchanged in 97% of these patients after 4 years. Most of the patients were women (four to one), and the diagnosis was almost always unsuspected by the referring physician. Physical exam was helpful in suggesting the diagnosis of abdominal wall pain.

The use of Carnett sign can be helpful. A positive Carnett sign is when abdominal pain increases or remains unchanged with tensing abdomen or when the examiner palpates the tensed abdomen. Thompson and colleagues looked at the outcome of 72 patients with undiagnosed abdominal pain and a positive Carnett sign.² Despite multiple diagnostic tests and surgeries done on these patients, very few of them had serious underlying pathology.

Thompson and Frances published another study looking at 120 patients presenting to an ED with undiagnosed abdominal pain.³ Twenty-four of the patients had positive abdominal wall tenderness on exam, and of those, only 1 had intra-abdominal pathology.

In another study, 158 patients admitted to the hospital with abdominal pain were evaluated for the presence of abdominal wall pain.⁴ Fifty-three patients were diagnosed with appendicitis, and 5 had abdominal wall tenderness on exam. Thirty-eight patients had other intra-abdominal pathology, and none of those had abdominal wall tenderness on exam. Of the 67 patients in the study who had nonspecific abdominal pain, 19 had abdominal wall tenderness on exam.

Most physicians do not include evaluation for abdominal wall tenderness as part of their evaluation of patients with abdominal pain. I think looking for this is helpful and, if positive, may lead to a diagnosis, as well as reduce the likelihood of intra-abdominal diagnoses.
 

What can we do in regard to therapy for patients with an abdominal wall source of pain?

Many patients with abdominal wall pain have anterior cutaneous nerve entrapment syndrome (ACNES). Patient’s with this often have discrete areas of tenderness on exam, often on the lateral edge of the rectus sheath, frequently on the right side of the abdomen. Anesthetic injection at the point of tenderness provides immediate relief for patients with ACNES, and is helpful in confirming the diagnosis.

Boelens and colleagues did injections in 48 patients suspected of having ACNE, randomizing half to receive lidocaine and half to receive saline placebo.5The majority of the patients receiving lidocaine (54%) had a response, compared with 17% of placebo patients (P less than .007).

Greenbaum and colleagues studied 79 patients with chronic abdominal wall pain.⁶ In this study, 72 of 79 patients had greater than 50% pain relief with anesthetic injection and were followed for a mean of almost 14 months. Only four of these patients ended up having a visceral cause of pain.
 

Can using injections help pain from ACNES longer term?

Koop and colleagues looked at all published studies in regards to both immediate and longer-term pain relief with injections.⁷ Both lidocaine injections and injections with lidocaine plus steroids led to long-term pain relief (40%-50% of patients with multiple lidocaine injections and up to 80% with lidocaine plus steroid injections). I think that injections are certainly worth a try in patients with chronic abdominal wall pain.

Pearl

Consider chronic abdominal wall pain in your differential diagnoses for patients with chronic abdominal pain, and use Carnett sign to help with diagnosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Costanza CD et al. Clin Gastroenterol Hepatol. 2004 May;2(5):395-9.

2. Thomson WH et al. Br J Surg. 1991 Feb;78(2):223-5.

3. Thomson H, Francis DM. Lancet. 1977 Nov 19;2(8047):1053-4.

4. Gray DW et al. Ann R Coll Surg Engl. 1988 Jul;70(4):233-4.

5. Boelens OB et al. Br J Surg. 2013 Jan;100(2):217-21.

6. Greenbaum DS et al. Dig Dis Sci. 1994 Sep;39(9):1935-41.

7. Koop H et al. Dtsch Arztebl Int. 2016 Jan 29;113(4):51-7.


 

A 53-year-old woman presents for evaluation of persistent abdominal pain over the past 6 months. She reports the pain is about a 7 out of 10, located in the right upper quadrant. The pain does not worsen with food and not relieved with bowel movements. She has no nausea or vomiting. She reports that the pain worsens when she is sitting or standing and is relieved by lying down. Her past medical history includes having had a cholecystectomy in 2016, having hypertension, and having type 2 diabetes mellitus.

The patient’s medications include metformin, lisinopril, and empagliflozin. Her blood pressure was 130/70, and her pulse was 80. An abdominal exam of her found tenderness to palpation in the right upper quadrant, and no rebound tenderness. Her labs found a white blood cell count of 5.4, a hematocrit of 44%, an erythrocyte sedimentation rate of 13, a C-reactive protein of 1.0, a bilirubin of .8, an alkaline phosphatase of 100, an aspartate aminotransferase of 30, and an alanine transaminase of 22.



What is the most appropriate next step?

A) Right side up oblique ultrasound.

B) Abdominal CT scan.

C) Upper endoscopy.

D) More detailed physical exam.



The correct answer here is D, a more detailed physical exam is needed. Given the positional nature of this patient’s abdominal pain, an evaluation for an abdominal wall cause is appropriate.

Abdominal wall pain as a cause of chronic abdominal pain is rarely considered, but it really should be. Costanza and colleagues looked at 2,709 patients referred to gastroenterologists for chronic abdominal pain.¹ Chronic abdominal wall pain was diagnosed in 137 patients, with the diagnosis unchanged in 97% of these patients after 4 years. Most of the patients were women (four to one), and the diagnosis was almost always unsuspected by the referring physician. Physical exam was helpful in suggesting the diagnosis of abdominal wall pain.

The use of Carnett sign can be helpful. A positive Carnett sign is when abdominal pain increases or remains unchanged with tensing abdomen or when the examiner palpates the tensed abdomen. Thompson and colleagues looked at the outcome of 72 patients with undiagnosed abdominal pain and a positive Carnett sign.² Despite multiple diagnostic tests and surgeries done on these patients, very few of them had serious underlying pathology.

Thompson and Frances published another study looking at 120 patients presenting to an ED with undiagnosed abdominal pain.³ Twenty-four of the patients had positive abdominal wall tenderness on exam, and of those, only 1 had intra-abdominal pathology.

In another study, 158 patients admitted to the hospital with abdominal pain were evaluated for the presence of abdominal wall pain.⁴ Fifty-three patients were diagnosed with appendicitis, and 5 had abdominal wall tenderness on exam. Thirty-eight patients had other intra-abdominal pathology, and none of those had abdominal wall tenderness on exam. Of the 67 patients in the study who had nonspecific abdominal pain, 19 had abdominal wall tenderness on exam.

Most physicians do not include evaluation for abdominal wall tenderness as part of their evaluation of patients with abdominal pain. I think looking for this is helpful and, if positive, may lead to a diagnosis, as well as reduce the likelihood of intra-abdominal diagnoses.
 

What can we do in regard to therapy for patients with an abdominal wall source of pain?

Many patients with abdominal wall pain have anterior cutaneous nerve entrapment syndrome (ACNES). Patient’s with this often have discrete areas of tenderness on exam, often on the lateral edge of the rectus sheath, frequently on the right side of the abdomen. Anesthetic injection at the point of tenderness provides immediate relief for patients with ACNES, and is helpful in confirming the diagnosis.

Boelens and colleagues did injections in 48 patients suspected of having ACNE, randomizing half to receive lidocaine and half to receive saline placebo.5The majority of the patients receiving lidocaine (54%) had a response, compared with 17% of placebo patients (P less than .007).

Greenbaum and colleagues studied 79 patients with chronic abdominal wall pain.⁶ In this study, 72 of 79 patients had greater than 50% pain relief with anesthetic injection and were followed for a mean of almost 14 months. Only four of these patients ended up having a visceral cause of pain.
 

Can using injections help pain from ACNES longer term?

Koop and colleagues looked at all published studies in regards to both immediate and longer-term pain relief with injections.⁷ Both lidocaine injections and injections with lidocaine plus steroids led to long-term pain relief (40%-50% of patients with multiple lidocaine injections and up to 80% with lidocaine plus steroid injections). I think that injections are certainly worth a try in patients with chronic abdominal wall pain.

Pearl

Consider chronic abdominal wall pain in your differential diagnoses for patients with chronic abdominal pain, and use Carnett sign to help with diagnosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Costanza CD et al. Clin Gastroenterol Hepatol. 2004 May;2(5):395-9.

2. Thomson WH et al. Br J Surg. 1991 Feb;78(2):223-5.

3. Thomson H, Francis DM. Lancet. 1977 Nov 19;2(8047):1053-4.

4. Gray DW et al. Ann R Coll Surg Engl. 1988 Jul;70(4):233-4.

5. Boelens OB et al. Br J Surg. 2013 Jan;100(2):217-21.

6. Greenbaum DS et al. Dig Dis Sci. 1994 Sep;39(9):1935-41.

7. Koop H et al. Dtsch Arztebl Int. 2016 Jan 29;113(4):51-7.


 

A 53-year-old woman presents for evaluation of persistent abdominal pain over the past 6 months. She reports the pain is about a 7 out of 10, located in the right upper quadrant. The pain does not worsen with food and not relieved with bowel movements. She has no nausea or vomiting. She reports that the pain worsens when she is sitting or standing and is relieved by lying down. Her past medical history includes having had a cholecystectomy in 2016, having hypertension, and having type 2 diabetes mellitus.

The patient’s medications include metformin, lisinopril, and empagliflozin. Her blood pressure was 130/70, and her pulse was 80. An abdominal exam of her found tenderness to palpation in the right upper quadrant, and no rebound tenderness. Her labs found a white blood cell count of 5.4, a hematocrit of 44%, an erythrocyte sedimentation rate of 13, a C-reactive protein of 1.0, a bilirubin of .8, an alkaline phosphatase of 100, an aspartate aminotransferase of 30, and an alanine transaminase of 22.



What is the most appropriate next step?

A) Right side up oblique ultrasound.

B) Abdominal CT scan.

C) Upper endoscopy.

D) More detailed physical exam.



The correct answer here is D, a more detailed physical exam is needed. Given the positional nature of this patient’s abdominal pain, an evaluation for an abdominal wall cause is appropriate.

Abdominal wall pain as a cause of chronic abdominal pain is rarely considered, but it really should be. Costanza and colleagues looked at 2,709 patients referred to gastroenterologists for chronic abdominal pain.¹ Chronic abdominal wall pain was diagnosed in 137 patients, with the diagnosis unchanged in 97% of these patients after 4 years. Most of the patients were women (four to one), and the diagnosis was almost always unsuspected by the referring physician. Physical exam was helpful in suggesting the diagnosis of abdominal wall pain.

The use of Carnett sign can be helpful. A positive Carnett sign is when abdominal pain increases or remains unchanged with tensing abdomen or when the examiner palpates the tensed abdomen. Thompson and colleagues looked at the outcome of 72 patients with undiagnosed abdominal pain and a positive Carnett sign.² Despite multiple diagnostic tests and surgeries done on these patients, very few of them had serious underlying pathology.

Thompson and Frances published another study looking at 120 patients presenting to an ED with undiagnosed abdominal pain.³ Twenty-four of the patients had positive abdominal wall tenderness on exam, and of those, only 1 had intra-abdominal pathology.

In another study, 158 patients admitted to the hospital with abdominal pain were evaluated for the presence of abdominal wall pain.⁴ Fifty-three patients were diagnosed with appendicitis, and 5 had abdominal wall tenderness on exam. Thirty-eight patients had other intra-abdominal pathology, and none of those had abdominal wall tenderness on exam. Of the 67 patients in the study who had nonspecific abdominal pain, 19 had abdominal wall tenderness on exam.

Most physicians do not include evaluation for abdominal wall tenderness as part of their evaluation of patients with abdominal pain. I think looking for this is helpful and, if positive, may lead to a diagnosis, as well as reduce the likelihood of intra-abdominal diagnoses.
 

What can we do in regard to therapy for patients with an abdominal wall source of pain?

Many patients with abdominal wall pain have anterior cutaneous nerve entrapment syndrome (ACNES). Patient’s with this often have discrete areas of tenderness on exam, often on the lateral edge of the rectus sheath, frequently on the right side of the abdomen. Anesthetic injection at the point of tenderness provides immediate relief for patients with ACNES, and is helpful in confirming the diagnosis.

Boelens and colleagues did injections in 48 patients suspected of having ACNE, randomizing half to receive lidocaine and half to receive saline placebo.5The majority of the patients receiving lidocaine (54%) had a response, compared with 17% of placebo patients (P less than .007).

Greenbaum and colleagues studied 79 patients with chronic abdominal wall pain.⁶ In this study, 72 of 79 patients had greater than 50% pain relief with anesthetic injection and were followed for a mean of almost 14 months. Only four of these patients ended up having a visceral cause of pain.
 

Can using injections help pain from ACNES longer term?

Koop and colleagues looked at all published studies in regards to both immediate and longer-term pain relief with injections.⁷ Both lidocaine injections and injections with lidocaine plus steroids led to long-term pain relief (40%-50% of patients with multiple lidocaine injections and up to 80% with lidocaine plus steroid injections). I think that injections are certainly worth a try in patients with chronic abdominal wall pain.

Pearl

Consider chronic abdominal wall pain in your differential diagnoses for patients with chronic abdominal pain, and use Carnett sign to help with diagnosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Costanza CD et al. Clin Gastroenterol Hepatol. 2004 May;2(5):395-9.

2. Thomson WH et al. Br J Surg. 1991 Feb;78(2):223-5.

3. Thomson H, Francis DM. Lancet. 1977 Nov 19;2(8047):1053-4.

4. Gray DW et al. Ann R Coll Surg Engl. 1988 Jul;70(4):233-4.

5. Boelens OB et al. Br J Surg. 2013 Jan;100(2):217-21.

6. Greenbaum DS et al. Dig Dis Sci. 1994 Sep;39(9):1935-41.

7. Koop H et al. Dtsch Arztebl Int. 2016 Jan 29;113(4):51-7.


 

I have had the pleasure of working on the Society of Hospital Medicine’s signature Leadership Academies since 2010, and I enjoy working with hospital medicine leaders from around the country every year. I started as a hospital medicine leader in 2000 and served during the unprecedented growth of the field when it was “the most rapidly growing specialty in the history of medicine.”

Most businesses dream of having a year of double-digit growth; my department grew an average of 15% annually for more than 10 years. These unique experiences have taught me many lessons and afforded me the opportunity to watch many stars of hospital medicine rise, as well as to learn from several less-scrupulous leaders about the darker side of hospital politics.

One of the lessons I learned the hard way about hospital politics is striking the “Authority/Accountability balance” in your career. I shared this perspective at the SHM annual conference in 2018, at speaking engagements on the West Coast, and with my leadership group at the academies. I am sharing it with you because the feedback I have received has been very positive.

The Authority/Accountability balance is a tool for evaluating your current career trajectory and measuring if it is set up for success or failure. The essence is that your Authority and Accountability need to be balanced for you to be successful in your career, regardless of your station. Everybody from the hospitalist fresh out of residency to the CEO needs to have Authority and Accountability in balance to be successful. And as you use the tool to measure your own potential for success or failure, learn to apply it to those who report to you.

I believe the rising tide lifts all boats and the success of your subordinates, through mentoring and support, will add to your success. There is another, more cynical view of subordinates that can be identified using the Authority/Accountability balance, which I will address.
 

Authority

In this construct, “Authority” has a much broader meaning than just the ability to tell people what to do. The ability to tell people what to do is important but not sufficient for success in hospital politics.

Financial resources are essential for a successful Authority/Accountability balance – not only the hardware such as computers, telephones, pagers, and so on, but also clerical support, technical support, and analytic support so that you are getting high-quality data on the performance of the members of your hospital medicine group (HMG). These “soft” resources (clerical, technical, and analytical) are often overlooked as needs that HMG leaders must advocate for; I speak with many HMG leaders who remain under-resourced with “soft” assets. However, being appropriately resourced in these areas can be transformational for a group. Hospitalists don’t like doing clerical work, and if you don’t like a menial job assigned to you, you probably won’t do it very well. Having an unlicensed person dedicated to these clerical activities not only will cost less, but will ensure the job is done better.

Reporting structure is critically important, often overlooked, and historically misaligned in HMGs. When hospital medicine was starting in the late 1990s and early 2000s, rapidly growing hospitalist groups were typically led by young, early-career physicians who had chosen hospital medicine as a career. The problem was that they often lacked the seniority and connections at the executive level to advocate for their HMG. All too often the hospitalist group was tucked in under another department or division which, in turn, reported HMG updates and issues to the board of directors and the CEO.

A common reporting structure in the early days was that a senior member of the medical staff, or group, had once worked in the hospital and therefore “understood” the issues and challenges that the hospitalists were facing. It was up to this physician with seniority and connections to advocate for the hospitalists as they saw fit. The problem was that the hospital landscape was, and is, constantly evolving in innumerable ways. These “once removed” reporting structures for HMGs failed to get the required information on the rapidly changing, and evolving, hospitalist landscape to the desks of executives who had the financial and structural control to address the challenges that the hospitalists in the trenches were facing.

Numerous HMGs failed in the early days of hospital medicine because of this type of misaligned reporting structure. This is a lesson that should not be forgotten: Make sure your HMG leader has a seat at the table where executive decisions are made, including but not limited to the board of directors. To be in balance, you have to be “in the room where it happens.”
 

Accountability

The outcomes that you are responsible for need to be explicit, appropriately resourced with Authority, and clearly spelled out in your job description. Your job description is a document you should know, own, and revisit regularly with whomever you report to, in order to ensure success.

Once you have the Authority side of the equation appropriately resourced, setting outcomes that are a stretch, but still realistic and achievable within the scope of your position, is critical to your success. It is good to think about short-, medium-, and long-term goals, especially if you are in a leadership role. For example, one expectation you will have, regardless of your station, is that you keep up on your email and answer your phone. These are short-term goals that will often be included in your job description. However, taking on a new hospital contract and making sure that it has 24/7 hospitalist coverage, that all the hospitalists are meeting the geometric mean length of stay, and that all the physicians are having 15 encounters per day doesn’t happen immediately. Long-term goals, such as taking on a new hospital contract, are the big-picture stuff that can make or break the career of an HMG leader. Long-term goals also need to be delineated in the job description, along with specific time stamps and the resources you need to accomplish big ticket items – which are spelled out in the Authority side (that is, physician recruiter, secretary, background checks, and so on).

One of the classic misuses of Accountability is the “Fall Guy” scenario. The Fall Guy scenario is often used by cynical hospital and medical group executives to expand their influence while limiting their liability. In the Fall Guy scenario, the executive is surrounded with junior partners who are underpowered with Authority, and then the executive makes decisions for which the junior partners are Accountable. This allows the senior executive to make risky decisions on behalf of the hospital or medical group without the liability of being held accountable when the decision-making process fails. When the risky, and often ill-informed, decision fails, the junior partner who lacked the Authority to make the decision – but held the Accountability for it – becomes the Fall Guy for the failed endeavor. This is a critical outcome that the Authority/Accountability balance can help you avoid, if you use it wisely and properly.

If you find yourself in the Fall Guy position, it is time for a change. The Authority, the Accountability, or both need to change so that they are in better balance. Or your employer needs to change. Changing employers is an outcome worth avoiding, if at all possible. I have scrutinized thousands of resumes in my career, and frequent job changes always wave a red flag to prospective employers. However, changing jobs remains a crucial option if you are being set up for failure when Authority and Accountability are out of balance.

If you are unable to negotiate for the balance that will allow you to be successful with your current group, remember that HMG leaders are a prized commodity and in short supply. Leaving a group that has been your career is hard, but it is better to leave than stay in a position where you are set up for failure as the Fall Guy. Further, the most effective time to expand your Authority is when you are negotiating the terms of a new position. Changing positions is the nuclear option. However, it is better than becoming the Fall Guy, and a change can create opportunities that will accelerate your career and influence, if done right.

When I talk about Authority/Accountability balance, I always counter the Fall Guy with an ignominious historical figure: General George B. McClellan. General McClellan was the commander of the Army of the Potomac during the early years of the American Civil War. General McClellan had the industrial might of the Union north at his beck and call, as well as extraordinary resources for recruiting and retaining soldiers for his army. At every encounter with General Robert E. Lee’s Army of Northern Virginia, General McClellan outnumbered them, sometimes by more than two to one. Yet General McClellan was outfoxed repeatedly for the same reason: He failed to take decisive action.

Every time that McClellan failed, he blamed insufficient resources and told President Lincoln that he needed more troops and more equipment to be successful. In summary, while the Fall Guy scenario needs to be avoided, once you are adequately resourced, success requires taking decisive and strategic action, or you will suffer as did General McClellan. Failing to act when you are appropriately resourced can be just as damaging to your career and credibility as allowing yourself to become the Fall Guy.
 

Job description

Everybody has somebody that they report to, no matter how high up on the executive ladder they have climbed. Even the CEO must report to the board of directors. And that reporting structure usually involves periodic formal reviews. Your formal review is a good time to go over your job description, note what is relevant, remove what is irrelevant, and add new elements that have evolved in importance since your last review.

Job descriptions take many forms, but they always include a list of qualifications. If you have the job, you have the qualifications, so that is not likely to change. You may become more qualified for a higher-level position, but that is an entirely different discussion. I like to think of a well-written job description as including short-term and long-term goals. Short-term goals are usually the daily stuff that keeps operations running smoothly but garners little attention. Examples would include staying current on your emails, answering your phone, organizing meetings, and regularly attending various committees. Even some of these short-term goals can and will change over time. I always enjoyed quality oversight in my department, but as the department and my responsibilities grew, I realized I couldn’t do everything that I wanted to do. I needed to focus on the things only I could do and delegate those things that could be done by someone else, even though I wanted to continue doing them myself. I created a position for a clinical quality officer, and quality oversight moved off of my job description.

Long-term goals are the aspirational items, such as increasing market share, decreasing readmissions, improving patient satisfaction, and the like. Effective leaders are often focused on these aspirational, long-term goals, but they still must effectively execute their short-term goals. Stephen Covey outlines the dilemma with the “time management matrix” in his seminal work “The 7 Habits of Highly Effective People.” An in-depth discussion is beyond the scope of this article, but the time management matrix places tasks into one of four categories based on urgency and importance, and provides strategies for staying up on short-term goals while continually moving long-term goals forward.If you show up at your review with a list of accomplishments as well as an understanding of how the “time management matrix” affects your responsibilities, your boss will be impressed. It is also worth mentioning that Covey’s first habit is “Proactivity.” He uses the term Proactivity in a much more nuanced form than we typically think of, however. Simply put, Proactivity is the opposite of Reactivity, and it is another invaluable tool for success with those long-term goals that will help you make a name for yourself.

When you show up for your review, be it annual, biannual, or other, be prepared. Not only should you bring your job description and recommendations for how it should be adapted in the changing environment, but also bring examples of your accomplishments since the last review.

I talk with leaders frequently who are hardworking and diligent and hate bragging about their achievements; I get that. At the same time, if you don’t inform your superiors about your successes, there is no guarantee that they will hear about them or understand them in the appropriate context. Bragging about how great you are in the physician’s lounge is annoying; telling your boss about your accomplishments since the last review is critical to maintaining the momentum of past accomplishments. If you are not willing to toot your own horn, there is a very good chance that your horn will remain silent. I don’t think self-promotion comes easily to anyone, and it has to be done with a degree of humility and sensitivity; but it has to be done, so prepare for it.
 

Look out for yourself and others

We talk about teamwork and collaboration as hospitalists, and SHM is always underscoring the importance of teamwork and highlighting examples of successful teamwork in its many conferences and publications. Most hospital executives are focused on their own careers, however, and many have no reservations about damaging your career (your brand) if they think it will promote theirs. You have to look out for yourself and size up every leadership position you get into.

Physicians can expect their careers to last decades. The average hospital CEO has a tenure of less than 3.5 years, however, and when a new CEO is hired, almost half of chief financial, chief operating, and chief information officers are fired within 9 months. You may be focused on the long-term success of your organization as you plan your career, but many hospital administrators are interested only in short-term gains. It is similar to some members of Congress who are interested only in what they need to do now to win the next election and not in the long-term needs of the country. You should understand this disconnect when dealing with hospital executives, and how you and your credibility can become cannon fodder in their quest for short-term self-preservation.

You have to look out for and take care of yourself as you promote your group. With a better understanding of the Authority/Accountability balance, you have new tools to assess your chances of success and to advocate for yourself so that you and your group can be successful.

Despite my cynicism toward executives in the medical field, I personally advocate for supporting the career development of those around you and advise against furthering your career at the expense of others. Many unscrupulous executives will use this approach, surrounding themselves with Fall Guys, but my experience shows that this is not a sustainable strategy for success. It can lead to short-term gains, but eventually the piper must be paid. Moreover, the most successful medical executives and leaders that I have encountered have been those who genuinely cared about their subordinates, looked out for them, and selflessly promoted their careers.

In the age of social media, tearing others down seems to be the fastest way to get more “likes.” However, I strongly believe that you can’t build up your group, and our profession, just by tearing people down. Lending a helping hand may bring you less attention in the short term, but such action raises your stature, creates loyalty, and leads to sustainable success for the long run.
 

Dr. McIlraith is the founding chairman of the Hospital Medicine Department at Mercy Medical Group in Sacramento, Calif. He received the SHM Award for Outstanding Service in Hospital Medicine in 2016 and is currently a member of the SHM Practice Management and Awards Committees, as well as the SHM Critical Care Task Force.

Sources

Quinn R. HM Turns 20: A look at the evolution of hospital medicine. The Hospitalist. 2016 August. https://www.the-hospitalist.org/hospitalist/article/121525/hm-turns-20-look-evolution-hospital-medicine

Stephen R. Covey. The 7 Habits of Highly Effective People: Powerful Lessons in Personal Change. Simon & Schuster. 1989.

10 Statistics on CEO Turnover, Recruitment. Becker’s Hospital Review. 2020. https://www.beckershospitalreview.com/hospital-management-administration/10-statistics-on-ceo-turnover-recruitment.html

I have had the pleasure of working on the Society of Hospital Medicine’s signature Leadership Academies since 2010, and I enjoy working with hospital medicine leaders from around the country every year. I started as a hospital medicine leader in 2000 and served during the unprecedented growth of the field when it was “the most rapidly growing specialty in the history of medicine.”

Most businesses dream of having a year of double-digit growth; my department grew an average of 15% annually for more than 10 years. These unique experiences have taught me many lessons and afforded me the opportunity to watch many stars of hospital medicine rise, as well as to learn from several less-scrupulous leaders about the darker side of hospital politics.

One of the lessons I learned the hard way about hospital politics is striking the “Authority/Accountability balance” in your career. I shared this perspective at the SHM annual conference in 2018, at speaking engagements on the West Coast, and with my leadership group at the academies. I am sharing it with you because the feedback I have received has been very positive.

The Authority/Accountability balance is a tool for evaluating your current career trajectory and measuring if it is set up for success or failure. The essence is that your Authority and Accountability need to be balanced for you to be successful in your career, regardless of your station. Everybody from the hospitalist fresh out of residency to the CEO needs to have Authority and Accountability in balance to be successful. And as you use the tool to measure your own potential for success or failure, learn to apply it to those who report to you.

I believe the rising tide lifts all boats and the success of your subordinates, through mentoring and support, will add to your success. There is another, more cynical view of subordinates that can be identified using the Authority/Accountability balance, which I will address.
 

Authority

In this construct, “Authority” has a much broader meaning than just the ability to tell people what to do. The ability to tell people what to do is important but not sufficient for success in hospital politics.

Financial resources are essential for a successful Authority/Accountability balance – not only the hardware such as computers, telephones, pagers, and so on, but also clerical support, technical support, and analytic support so that you are getting high-quality data on the performance of the members of your hospital medicine group (HMG). These “soft” resources (clerical, technical, and analytical) are often overlooked as needs that HMG leaders must advocate for; I speak with many HMG leaders who remain under-resourced with “soft” assets. However, being appropriately resourced in these areas can be transformational for a group. Hospitalists don’t like doing clerical work, and if you don’t like a menial job assigned to you, you probably won’t do it very well. Having an unlicensed person dedicated to these clerical activities not only will cost less, but will ensure the job is done better.

Reporting structure is critically important, often overlooked, and historically misaligned in HMGs. When hospital medicine was starting in the late 1990s and early 2000s, rapidly growing hospitalist groups were typically led by young, early-career physicians who had chosen hospital medicine as a career. The problem was that they often lacked the seniority and connections at the executive level to advocate for their HMG. All too often the hospitalist group was tucked in under another department or division which, in turn, reported HMG updates and issues to the board of directors and the CEO.

A common reporting structure in the early days was that a senior member of the medical staff, or group, had once worked in the hospital and therefore “understood” the issues and challenges that the hospitalists were facing. It was up to this physician with seniority and connections to advocate for the hospitalists as they saw fit. The problem was that the hospital landscape was, and is, constantly evolving in innumerable ways. These “once removed” reporting structures for HMGs failed to get the required information on the rapidly changing, and evolving, hospitalist landscape to the desks of executives who had the financial and structural control to address the challenges that the hospitalists in the trenches were facing.

Numerous HMGs failed in the early days of hospital medicine because of this type of misaligned reporting structure. This is a lesson that should not be forgotten: Make sure your HMG leader has a seat at the table where executive decisions are made, including but not limited to the board of directors. To be in balance, you have to be “in the room where it happens.”
 

Accountability

The outcomes that you are responsible for need to be explicit, appropriately resourced with Authority, and clearly spelled out in your job description. Your job description is a document you should know, own, and revisit regularly with whomever you report to, in order to ensure success.

Once you have the Authority side of the equation appropriately resourced, setting outcomes that are a stretch, but still realistic and achievable within the scope of your position, is critical to your success. It is good to think about short-, medium-, and long-term goals, especially if you are in a leadership role. For example, one expectation you will have, regardless of your station, is that you keep up on your email and answer your phone. These are short-term goals that will often be included in your job description. However, taking on a new hospital contract and making sure that it has 24/7 hospitalist coverage, that all the hospitalists are meeting the geometric mean length of stay, and that all the physicians are having 15 encounters per day doesn’t happen immediately. Long-term goals, such as taking on a new hospital contract, are the big-picture stuff that can make or break the career of an HMG leader. Long-term goals also need to be delineated in the job description, along with specific time stamps and the resources you need to accomplish big ticket items – which are spelled out in the Authority side (that is, physician recruiter, secretary, background checks, and so on).

One of the classic misuses of Accountability is the “Fall Guy” scenario. The Fall Guy scenario is often used by cynical hospital and medical group executives to expand their influence while limiting their liability. In the Fall Guy scenario, the executive is surrounded with junior partners who are underpowered with Authority, and then the executive makes decisions for which the junior partners are Accountable. This allows the senior executive to make risky decisions on behalf of the hospital or medical group without the liability of being held accountable when the decision-making process fails. When the risky, and often ill-informed, decision fails, the junior partner who lacked the Authority to make the decision – but held the Accountability for it – becomes the Fall Guy for the failed endeavor. This is a critical outcome that the Authority/Accountability balance can help you avoid, if you use it wisely and properly.

If you find yourself in the Fall Guy position, it is time for a change. The Authority, the Accountability, or both need to change so that they are in better balance. Or your employer needs to change. Changing employers is an outcome worth avoiding, if at all possible. I have scrutinized thousands of resumes in my career, and frequent job changes always wave a red flag to prospective employers. However, changing jobs remains a crucial option if you are being set up for failure when Authority and Accountability are out of balance.

If you are unable to negotiate for the balance that will allow you to be successful with your current group, remember that HMG leaders are a prized commodity and in short supply. Leaving a group that has been your career is hard, but it is better to leave than stay in a position where you are set up for failure as the Fall Guy. Further, the most effective time to expand your Authority is when you are negotiating the terms of a new position. Changing positions is the nuclear option. However, it is better than becoming the Fall Guy, and a change can create opportunities that will accelerate your career and influence, if done right.

When I talk about Authority/Accountability balance, I always counter the Fall Guy with an ignominious historical figure: General George B. McClellan. General McClellan was the commander of the Army of the Potomac during the early years of the American Civil War. General McClellan had the industrial might of the Union north at his beck and call, as well as extraordinary resources for recruiting and retaining soldiers for his army. At every encounter with General Robert E. Lee’s Army of Northern Virginia, General McClellan outnumbered them, sometimes by more than two to one. Yet General McClellan was outfoxed repeatedly for the same reason: He failed to take decisive action.

Every time that McClellan failed, he blamed insufficient resources and told President Lincoln that he needed more troops and more equipment to be successful. In summary, while the Fall Guy scenario needs to be avoided, once you are adequately resourced, success requires taking decisive and strategic action, or you will suffer as did General McClellan. Failing to act when you are appropriately resourced can be just as damaging to your career and credibility as allowing yourself to become the Fall Guy.
 

Job description

Everybody has somebody that they report to, no matter how high up on the executive ladder they have climbed. Even the CEO must report to the board of directors. And that reporting structure usually involves periodic formal reviews. Your formal review is a good time to go over your job description, note what is relevant, remove what is irrelevant, and add new elements that have evolved in importance since your last review.

Job descriptions take many forms, but they always include a list of qualifications. If you have the job, you have the qualifications, so that is not likely to change. You may become more qualified for a higher-level position, but that is an entirely different discussion. I like to think of a well-written job description as including short-term and long-term goals. Short-term goals are usually the daily stuff that keeps operations running smoothly but garners little attention. Examples would include staying current on your emails, answering your phone, organizing meetings, and regularly attending various committees. Even some of these short-term goals can and will change over time. I always enjoyed quality oversight in my department, but as the department and my responsibilities grew, I realized I couldn’t do everything that I wanted to do. I needed to focus on the things only I could do and delegate those things that could be done by someone else, even though I wanted to continue doing them myself. I created a position for a clinical quality officer, and quality oversight moved off of my job description.

Long-term goals are the aspirational items, such as increasing market share, decreasing readmissions, improving patient satisfaction, and the like. Effective leaders are often focused on these aspirational, long-term goals, but they still must effectively execute their short-term goals. Stephen Covey outlines the dilemma with the “time management matrix” in his seminal work “The 7 Habits of Highly Effective People.” An in-depth discussion is beyond the scope of this article, but the time management matrix places tasks into one of four categories based on urgency and importance, and provides strategies for staying up on short-term goals while continually moving long-term goals forward.If you show up at your review with a list of accomplishments as well as an understanding of how the “time management matrix” affects your responsibilities, your boss will be impressed. It is also worth mentioning that Covey’s first habit is “Proactivity.” He uses the term Proactivity in a much more nuanced form than we typically think of, however. Simply put, Proactivity is the opposite of Reactivity, and it is another invaluable tool for success with those long-term goals that will help you make a name for yourself.

When you show up for your review, be it annual, biannual, or other, be prepared. Not only should you bring your job description and recommendations for how it should be adapted in the changing environment, but also bring examples of your accomplishments since the last review.

I talk with leaders frequently who are hardworking and diligent and hate bragging about their achievements; I get that. At the same time, if you don’t inform your superiors about your successes, there is no guarantee that they will hear about them or understand them in the appropriate context. Bragging about how great you are in the physician’s lounge is annoying; telling your boss about your accomplishments since the last review is critical to maintaining the momentum of past accomplishments. If you are not willing to toot your own horn, there is a very good chance that your horn will remain silent. I don’t think self-promotion comes easily to anyone, and it has to be done with a degree of humility and sensitivity; but it has to be done, so prepare for it.
 

Look out for yourself and others

We talk about teamwork and collaboration as hospitalists, and SHM is always underscoring the importance of teamwork and highlighting examples of successful teamwork in its many conferences and publications. Most hospital executives are focused on their own careers, however, and many have no reservations about damaging your career (your brand) if they think it will promote theirs. You have to look out for yourself and size up every leadership position you get into.

Physicians can expect their careers to last decades. The average hospital CEO has a tenure of less than 3.5 years, however, and when a new CEO is hired, almost half of chief financial, chief operating, and chief information officers are fired within 9 months. You may be focused on the long-term success of your organization as you plan your career, but many hospital administrators are interested only in short-term gains. It is similar to some members of Congress who are interested only in what they need to do now to win the next election and not in the long-term needs of the country. You should understand this disconnect when dealing with hospital executives, and how you and your credibility can become cannon fodder in their quest for short-term self-preservation.

You have to look out for and take care of yourself as you promote your group. With a better understanding of the Authority/Accountability balance, you have new tools to assess your chances of success and to advocate for yourself so that you and your group can be successful.

Despite my cynicism toward executives in the medical field, I personally advocate for supporting the career development of those around you and advise against furthering your career at the expense of others. Many unscrupulous executives will use this approach, surrounding themselves with Fall Guys, but my experience shows that this is not a sustainable strategy for success. It can lead to short-term gains, but eventually the piper must be paid. Moreover, the most successful medical executives and leaders that I have encountered have been those who genuinely cared about their subordinates, looked out for them, and selflessly promoted their careers.

In the age of social media, tearing others down seems to be the fastest way to get more “likes.” However, I strongly believe that you can’t build up your group, and our profession, just by tearing people down. Lending a helping hand may bring you less attention in the short term, but such action raises your stature, creates loyalty, and leads to sustainable success for the long run.
 

Dr. McIlraith is the founding chairman of the Hospital Medicine Department at Mercy Medical Group in Sacramento, Calif. He received the SHM Award for Outstanding Service in Hospital Medicine in 2016 and is currently a member of the SHM Practice Management and Awards Committees, as well as the SHM Critical Care Task Force.

Sources

Quinn R. HM Turns 20: A look at the evolution of hospital medicine. The Hospitalist. 2016 August. https://www.the-hospitalist.org/hospitalist/article/121525/hm-turns-20-look-evolution-hospital-medicine

Stephen R. Covey. The 7 Habits of Highly Effective People: Powerful Lessons in Personal Change. Simon & Schuster. 1989.

10 Statistics on CEO Turnover, Recruitment. Becker’s Hospital Review. 2020. https://www.beckershospitalreview.com/hospital-management-administration/10-statistics-on-ceo-turnover-recruitment.html

I have had the pleasure of working on the Society of Hospital Medicine’s signature Leadership Academies since 2010, and I enjoy working with hospital medicine leaders from around the country every year. I started as a hospital medicine leader in 2000 and served during the unprecedented growth of the field when it was “the most rapidly growing specialty in the history of medicine.”

Most businesses dream of having a year of double-digit growth; my department grew an average of 15% annually for more than 10 years. These unique experiences have taught me many lessons and afforded me the opportunity to watch many stars of hospital medicine rise, as well as to learn from several less-scrupulous leaders about the darker side of hospital politics.

One of the lessons I learned the hard way about hospital politics is striking the “Authority/Accountability balance” in your career. I shared this perspective at the SHM annual conference in 2018, at speaking engagements on the West Coast, and with my leadership group at the academies. I am sharing it with you because the feedback I have received has been very positive.

The Authority/Accountability balance is a tool for evaluating your current career trajectory and measuring if it is set up for success or failure. The essence is that your Authority and Accountability need to be balanced for you to be successful in your career, regardless of your station. Everybody from the hospitalist fresh out of residency to the CEO needs to have Authority and Accountability in balance to be successful. And as you use the tool to measure your own potential for success or failure, learn to apply it to those who report to you.

I believe the rising tide lifts all boats and the success of your subordinates, through mentoring and support, will add to your success. There is another, more cynical view of subordinates that can be identified using the Authority/Accountability balance, which I will address.
 

Authority

In this construct, “Authority” has a much broader meaning than just the ability to tell people what to do. The ability to tell people what to do is important but not sufficient for success in hospital politics.

Financial resources are essential for a successful Authority/Accountability balance – not only the hardware such as computers, telephones, pagers, and so on, but also clerical support, technical support, and analytic support so that you are getting high-quality data on the performance of the members of your hospital medicine group (HMG). These “soft” resources (clerical, technical, and analytical) are often overlooked as needs that HMG leaders must advocate for; I speak with many HMG leaders who remain under-resourced with “soft” assets. However, being appropriately resourced in these areas can be transformational for a group. Hospitalists don’t like doing clerical work, and if you don’t like a menial job assigned to you, you probably won’t do it very well. Having an unlicensed person dedicated to these clerical activities not only will cost less, but will ensure the job is done better.

Reporting structure is critically important, often overlooked, and historically misaligned in HMGs. When hospital medicine was starting in the late 1990s and early 2000s, rapidly growing hospitalist groups were typically led by young, early-career physicians who had chosen hospital medicine as a career. The problem was that they often lacked the seniority and connections at the executive level to advocate for their HMG. All too often the hospitalist group was tucked in under another department or division which, in turn, reported HMG updates and issues to the board of directors and the CEO.

A common reporting structure in the early days was that a senior member of the medical staff, or group, had once worked in the hospital and therefore “understood” the issues and challenges that the hospitalists were facing. It was up to this physician with seniority and connections to advocate for the hospitalists as they saw fit. The problem was that the hospital landscape was, and is, constantly evolving in innumerable ways. These “once removed” reporting structures for HMGs failed to get the required information on the rapidly changing, and evolving, hospitalist landscape to the desks of executives who had the financial and structural control to address the challenges that the hospitalists in the trenches were facing.

Numerous HMGs failed in the early days of hospital medicine because of this type of misaligned reporting structure. This is a lesson that should not be forgotten: Make sure your HMG leader has a seat at the table where executive decisions are made, including but not limited to the board of directors. To be in balance, you have to be “in the room where it happens.”
 

Accountability

The outcomes that you are responsible for need to be explicit, appropriately resourced with Authority, and clearly spelled out in your job description. Your job description is a document you should know, own, and revisit regularly with whomever you report to, in order to ensure success.

Once you have the Authority side of the equation appropriately resourced, setting outcomes that are a stretch, but still realistic and achievable within the scope of your position, is critical to your success. It is good to think about short-, medium-, and long-term goals, especially if you are in a leadership role. For example, one expectation you will have, regardless of your station, is that you keep up on your email and answer your phone. These are short-term goals that will often be included in your job description. However, taking on a new hospital contract and making sure that it has 24/7 hospitalist coverage, that all the hospitalists are meeting the geometric mean length of stay, and that all the physicians are having 15 encounters per day doesn’t happen immediately. Long-term goals, such as taking on a new hospital contract, are the big-picture stuff that can make or break the career of an HMG leader. Long-term goals also need to be delineated in the job description, along with specific time stamps and the resources you need to accomplish big ticket items – which are spelled out in the Authority side (that is, physician recruiter, secretary, background checks, and so on).

One of the classic misuses of Accountability is the “Fall Guy” scenario. The Fall Guy scenario is often used by cynical hospital and medical group executives to expand their influence while limiting their liability. In the Fall Guy scenario, the executive is surrounded with junior partners who are underpowered with Authority, and then the executive makes decisions for which the junior partners are Accountable. This allows the senior executive to make risky decisions on behalf of the hospital or medical group without the liability of being held accountable when the decision-making process fails. When the risky, and often ill-informed, decision fails, the junior partner who lacked the Authority to make the decision – but held the Accountability for it – becomes the Fall Guy for the failed endeavor. This is a critical outcome that the Authority/Accountability balance can help you avoid, if you use it wisely and properly.

If you find yourself in the Fall Guy position, it is time for a change. The Authority, the Accountability, or both need to change so that they are in better balance. Or your employer needs to change. Changing employers is an outcome worth avoiding, if at all possible. I have scrutinized thousands of resumes in my career, and frequent job changes always wave a red flag to prospective employers. However, changing jobs remains a crucial option if you are being set up for failure when Authority and Accountability are out of balance.

If you are unable to negotiate for the balance that will allow you to be successful with your current group, remember that HMG leaders are a prized commodity and in short supply. Leaving a group that has been your career is hard, but it is better to leave than stay in a position where you are set up for failure as the Fall Guy. Further, the most effective time to expand your Authority is when you are negotiating the terms of a new position. Changing positions is the nuclear option. However, it is better than becoming the Fall Guy, and a change can create opportunities that will accelerate your career and influence, if done right.

When I talk about Authority/Accountability balance, I always counter the Fall Guy with an ignominious historical figure: General George B. McClellan. General McClellan was the commander of the Army of the Potomac during the early years of the American Civil War. General McClellan had the industrial might of the Union north at his beck and call, as well as extraordinary resources for recruiting and retaining soldiers for his army. At every encounter with General Robert E. Lee’s Army of Northern Virginia, General McClellan outnumbered them, sometimes by more than two to one. Yet General McClellan was outfoxed repeatedly for the same reason: He failed to take decisive action.

Every time that McClellan failed, he blamed insufficient resources and told President Lincoln that he needed more troops and more equipment to be successful. In summary, while the Fall Guy scenario needs to be avoided, once you are adequately resourced, success requires taking decisive and strategic action, or you will suffer as did General McClellan. Failing to act when you are appropriately resourced can be just as damaging to your career and credibility as allowing yourself to become the Fall Guy.
 

Job description

Everybody has somebody that they report to, no matter how high up on the executive ladder they have climbed. Even the CEO must report to the board of directors. And that reporting structure usually involves periodic formal reviews. Your formal review is a good time to go over your job description, note what is relevant, remove what is irrelevant, and add new elements that have evolved in importance since your last review.

Job descriptions take many forms, but they always include a list of qualifications. If you have the job, you have the qualifications, so that is not likely to change. You may become more qualified for a higher-level position, but that is an entirely different discussion. I like to think of a well-written job description as including short-term and long-term goals. Short-term goals are usually the daily stuff that keeps operations running smoothly but garners little attention. Examples would include staying current on your emails, answering your phone, organizing meetings, and regularly attending various committees. Even some of these short-term goals can and will change over time. I always enjoyed quality oversight in my department, but as the department and my responsibilities grew, I realized I couldn’t do everything that I wanted to do. I needed to focus on the things only I could do and delegate those things that could be done by someone else, even though I wanted to continue doing them myself. I created a position for a clinical quality officer, and quality oversight moved off of my job description.

Long-term goals are the aspirational items, such as increasing market share, decreasing readmissions, improving patient satisfaction, and the like. Effective leaders are often focused on these aspirational, long-term goals, but they still must effectively execute their short-term goals. Stephen Covey outlines the dilemma with the “time management matrix” in his seminal work “The 7 Habits of Highly Effective People.” An in-depth discussion is beyond the scope of this article, but the time management matrix places tasks into one of four categories based on urgency and importance, and provides strategies for staying up on short-term goals while continually moving long-term goals forward.If you show up at your review with a list of accomplishments as well as an understanding of how the “time management matrix” affects your responsibilities, your boss will be impressed. It is also worth mentioning that Covey’s first habit is “Proactivity.” He uses the term Proactivity in a much more nuanced form than we typically think of, however. Simply put, Proactivity is the opposite of Reactivity, and it is another invaluable tool for success with those long-term goals that will help you make a name for yourself.

When you show up for your review, be it annual, biannual, or other, be prepared. Not only should you bring your job description and recommendations for how it should be adapted in the changing environment, but also bring examples of your accomplishments since the last review.

I talk with leaders frequently who are hardworking and diligent and hate bragging about their achievements; I get that. At the same time, if you don’t inform your superiors about your successes, there is no guarantee that they will hear about them or understand them in the appropriate context. Bragging about how great you are in the physician’s lounge is annoying; telling your boss about your accomplishments since the last review is critical to maintaining the momentum of past accomplishments. If you are not willing to toot your own horn, there is a very good chance that your horn will remain silent. I don’t think self-promotion comes easily to anyone, and it has to be done with a degree of humility and sensitivity; but it has to be done, so prepare for it.
 

Look out for yourself and others

We talk about teamwork and collaboration as hospitalists, and SHM is always underscoring the importance of teamwork and highlighting examples of successful teamwork in its many conferences and publications. Most hospital executives are focused on their own careers, however, and many have no reservations about damaging your career (your brand) if they think it will promote theirs. You have to look out for yourself and size up every leadership position you get into.

Physicians can expect their careers to last decades. The average hospital CEO has a tenure of less than 3.5 years, however, and when a new CEO is hired, almost half of chief financial, chief operating, and chief information officers are fired within 9 months. You may be focused on the long-term success of your organization as you plan your career, but many hospital administrators are interested only in short-term gains. It is similar to some members of Congress who are interested only in what they need to do now to win the next election and not in the long-term needs of the country. You should understand this disconnect when dealing with hospital executives, and how you and your credibility can become cannon fodder in their quest for short-term self-preservation.

You have to look out for and take care of yourself as you promote your group. With a better understanding of the Authority/Accountability balance, you have new tools to assess your chances of success and to advocate for yourself so that you and your group can be successful.

Despite my cynicism toward executives in the medical field, I personally advocate for supporting the career development of those around you and advise against furthering your career at the expense of others. Many unscrupulous executives will use this approach, surrounding themselves with Fall Guys, but my experience shows that this is not a sustainable strategy for success. It can lead to short-term gains, but eventually the piper must be paid. Moreover, the most successful medical executives and leaders that I have encountered have been those who genuinely cared about their subordinates, looked out for them, and selflessly promoted their careers.

In the age of social media, tearing others down seems to be the fastest way to get more “likes.” However, I strongly believe that you can’t build up your group, and our profession, just by tearing people down. Lending a helping hand may bring you less attention in the short term, but such action raises your stature, creates loyalty, and leads to sustainable success for the long run.
 

Dr. McIlraith is the founding chairman of the Hospital Medicine Department at Mercy Medical Group in Sacramento, Calif. He received the SHM Award for Outstanding Service in Hospital Medicine in 2016 and is currently a member of the SHM Practice Management and Awards Committees, as well as the SHM Critical Care Task Force.

Sources

Quinn R. HM Turns 20: A look at the evolution of hospital medicine. The Hospitalist. 2016 August. https://www.the-hospitalist.org/hospitalist/article/121525/hm-turns-20-look-evolution-hospital-medicine

Stephen R. Covey. The 7 Habits of Highly Effective People: Powerful Lessons in Personal Change. Simon & Schuster. 1989.

10 Statistics on CEO Turnover, Recruitment. Becker’s Hospital Review. 2020. https://www.beckershospitalreview.com/hospital-management-administration/10-statistics-on-ceo-turnover-recruitment.html

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Dear colleagues and friends,

Charles Kahi, MD, MS, AGAF, professor of medicine, Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.

IBD can be treated with diet alone

Inflammatory bowel diseases (IBD), comprising Crohn’s disease and ulcerative colitis, have emerged as global diseases. The past 3 decades have seen a rising incidence of these diseases not just in the Western hemisphere, where their prevalence has been well recognized, but also in regions of the world such as Asia and South America where they were previously rare. Whereas several possible factors have been proposed to explain this rising incidence and globalization of disease with varying degrees of supportive evidence, one of the most likely factors is a changing diet. Over the same period that the disease incidence and prevalence have risen, diets worldwide have converged with several common trends observed across countries and continents. These include reductions in dietary fiber, fruits, and vegetables, and increased intake of processed food, animal protein, fats, and sugary drinks, all of which have been linked epidemiologically to Crohn’s disease.

Treatment of Crohn’s disease and ulcerative colitis over the past 2 decades has focused on the immunologic dysfunction observed in these patients. Successful treatment has relied on suppressing immune responses either broadly or through targeted suppression of specific immunologic pathways. By and large, whereas these approaches have enabled us to make significant progress in reducing disease-related morbidity, success has been moderate at best, with fewer than half of patients in any clinical trial achieving remission at the end of a year. Thus, this approach alone may not be sufficient for most patients with IBD.

Treatment of IBD with diet was long considered out of the mainstream and confined to the realm of anecdotes and message boards. Despite most patients believing that diet played a role in development of IBD and onset of flares and that dietary modification was helpful in relieving symptoms, physicians – who for the most part were not trained in these approaches – were not believers, and probably rightly so in the absence of any supporting data.¹ However, the parallel emergence of three bodies of literature has now brought diet back into the mainstream of IBD care (such that not a single IBD conference goes by without at least a session or two on diet). First, large prospective cohorts from Europe and North America provided robust evidence linking long-term adult dietary patterns to disease incidence in adult-onset IBD, which supports many important case-control observations made over the past 2 decades.² Second, and perhaps most important, we began understanding the role of the microbiome in the development of these diseases and recognizing its centrality to bowel inflammation. One of the key determinants of the microbiome is diet, exerting both short-term and long-term influences on the microbial structure. While microbial changes are by no means the only mechanism through which diet can influence intestinal inflammation, they are among the most important, with broad effects across many dietary components. These findings provided a robust scientific basis for investigating the role of diet. Third, while still far from the high-quality (and expensive) set-up of investigational trials of pharmacologic therapies, dietary therapy studies have also evolved to randomized controlled trial designs and investigation of mechanism-driven dietary combinations. Together, I think these three recent advances, in addition to the wealth of existing literature and anecdotal experience, have been important in moving diet (back) into the IBD mainstream.

So what evidence is there that diet is effective in the treatment of IBD? Randomized controlled trials published more than a decade ago demonstrated that exclusive enteral nutrition, wherein all table foods are eliminated from a diet and the patient relies on an elemental diet alone for nutrition, was effective in not just inducing clinical remission but also improving inflammatory biomarkers.³ With results replicated in several trials, exclusive enteral nutrition is, in many parts of the world, one of the first-line treatments for pediatric Crohn’s disease. That this has not been translated to longer-term maintenance therapy is not necessarily an indicator of lack of durable efficacy, but reflects the challenges of maintaining such a restrictive diet long term while living an active, normal life. However, more recent rigorous studies have demonstrated that the effects of exclusive enteral nutrition can be mimicked either by a selected, less-restrictive diet (such as CD-TREAT⁴), which is more sustainable, or by combining partial enteral nutrition with an elimination diet that is quite diverse (such as CDED⁵). The latter two are considerably more promising as longer-term dietary treatments for Crohn’s disease with durable efficacy in open-label studies and randomized trials.

What are my final arguments for diet being used as a treatment for IBD? With the exception of very restrictive ones, diets are generally safe. Of course, patients on restricted diets need monitoring for nutritional deficiencies, but this monitoring is likely less intense than that needed for many of our immunosuppressive therapies. Dietary therapies are not associated with an increase in risk of infections or malignancy (unlike our traditional immunosuppressive therapies), and consequently are much more likely to be accepted by our patients than what we are currently offering. In addition, the existing treatments are expensive and consequently difficult to sustain globally with the increasing burden of these diseases. On the other hand, as eating and dietary choices are a routine part of day-to-day life, dietary therapies are not likely to be associated with any excess costs.

Therefore, treating IBD with diet alone is supported by epidemiologic, mechanistic, and clinical evidence and is a safe, effective, and inexpensive alternative for our patients.
 

References

1. Zallot C et al. Inflamm Bowel Dis. 2013 Jan;19(1):66-72.

2. Sasson AN et al. Clin Gastroenterol Hepatol. 2019 Dec 5;S1542-3565(19)31394-1.

3. Wall CL et al. World J Gastroenterol. 2013;19:7652-60.

4. Svolos V et al. Gastroenterology. 2019;156:1354-67.e6.

5. Levine A et al. Gastroenterology. 2019;157:440-50.e8.

Dr. Ananthakrishnan is a gastroenterologist in the division of gastroenterology, Crohn’s and Colitis Center, Massachusetts General Hospital and Harvard Medical School, Boston. He is supported by funding from the Crohn’s and Colitis Foundation and the Chleck Family Foundation.

IBD can be treated with diet alone – No, it cannot!

The cause of IBD is not completely understood, but we believe something in our environment triggers a dysregulated immune response in individuals with a genetic predisposition to IBD. Among the environmental triggers commonly recognized, diet is considered an important trigger through its ability to affect the composition and health of the gut microbiome and host barrier function. Epidemiologic data support this assumption. Westernization of diet has been associated with the increasing incidence of IBD across the globe and in immigrants who move from developing countries to an industrialized country. Observational studies have shown diets higher in meat and polyunsaturated fatty acids and omega-6 fatty acids are associated with a higher risk for IBD, whereas diets high in fruits, vegetables, and other sources of dietary fiber have a lower risk of IBD.

A growing body of evidence supports the impact food can have on gut health, specifically in mouse IBD models, but it is challenging to translate findings from animal studies into dietary interventions for IBD patients. Mouse studies help us understand the mechanistic basis of how diet may affect IBD, but randomized clinical trials establishing their role in IBD are lacking. This is not surprising as dietary studies are challenging, particularly if done in a robust manner, given the difficulties of ensuring and measuring dietary compliance.

Exclusive enteral nutrition (EEN) has been studied the most rigorously of all diets in IBD and has demonstrated the greatest benefit, compared with other diet studies in IBD. EEN requires the intake of elemental, semi-elemental, or polymeric formulas to meet all nutritional requirements without additional intake of food for 6-8 weeks. Studies have been performed mostly in pediatric populations and have shown effectiveness in induction of remission with reduction in inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, and even mucosal healing. EEN has not worked out as well for adult populations, because of the poor tolerability of exclusive intake of enteral formulas. Because of this limitation, studies of partial enteral nutrition have been performed that generally allow some food intake in addition to the enteral nutrition. When compared with EEN or anti–tumor necrosis factor–alpha therapy, partial enteral nutrition is a less-effective treatment of Crohn’s disease; however, partial enteral nutrition does appear to improve clinical symptoms.

Beyond EEN, there are many diets that have been considered for the treatment of IBD, including the specific carbohydrate diet (SCD), Crohn’s disease exclusion diet, autoimmune diet, low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols), Paleolithic diet, Mediterranean diet, and the semi-vegetarian diet, to name a few. Of these, only the SCD and Crohn’s disease exclusion diets have shown improvement in clinical remission and reduction in inflammatory markers.

The SCD diet is based on the theory that malabsorption of disaccharide and polysaccharide carbohydrates leads to bacterial overgrowth and host barrier dysfunction. This diet eliminates grains, dairy, processed meats, and certain vegetables such as potatoes, yams, and legumes. Small uncontrolled studies have shown improvement in symptoms and endoscopy findings. However, this restrictive diet is nearly impossible to follow long term. The Crohn’s disease exclusion diet is a whole foods diet avoiding all processed foods, animal fats, dairy, and gluten. Small studies of this diet have also shown improvement in clinical symptoms and inflammatory markers.

The plethora of studies and reports of the therapeutic effect of diet on IBD provide some promise of the benefit dietary modifications can bring to our IBD patients. However, most dietary studies are underpowered, lack a control arm, and do not include endoscopic endpoints. The current body of evidence remains insufficient to support the use of diet alone for the treatment of IBD. We need randomized clinical controlled trials that are held to the same rigor as those of our approved medical treatments for IBD. Although such trials are challenging, we’ve seen groups rise to the task to carry out more robust dietary studies in the IBD population, and we await the results of several ongoing trials.

IBD is a challenging disease to live with and often leaves our patients feeling out of control. Dietary choices provide an avenue for patients to have some control of their health. However, current evidence does not support the prescription of dietary interventions alone to treat IBD, particularly when we have known, effective therapies. While I am not ready to prescribe diet as a stand-alone treatment for IBD, I make a point to discuss the role diet may play in helping our patients achieve optimal health. As health care providers, it is our responsibility to provide holistic care to our patients, which includes promotion of a healthy diet, absent processed foods and added sugars. Healthy lifestyle choices combined with effective medical and surgical treatments offer our patients the best shot at sustained disease control.
 

References

1. Hou JK et al. Am J Gastroenterol. 2011;106(4):563-73.

2. Zachos M et al. Cochrane Database Syst Rev. 2007(1):CD000542.

3. Lee D et al. Inflamm Bowel Dis. 2015;21(8):1786-93.

4. Obih C et al. Nutrition. 2016;32(4):418-25.

5. Sigall Boneh R et al. J Crohns Colitis. 2017;11(10):1205-12.

Dr. Raffals is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. She has no financial conflicts of interest relevant to this paper.

Dear colleagues and friends,

Charles Kahi, MD, MS, AGAF, professor of medicine, Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.

IBD can be treated with diet alone

Inflammatory bowel diseases (IBD), comprising Crohn’s disease and ulcerative colitis, have emerged as global diseases. The past 3 decades have seen a rising incidence of these diseases not just in the Western hemisphere, where their prevalence has been well recognized, but also in regions of the world such as Asia and South America where they were previously rare. Whereas several possible factors have been proposed to explain this rising incidence and globalization of disease with varying degrees of supportive evidence, one of the most likely factors is a changing diet. Over the same period that the disease incidence and prevalence have risen, diets worldwide have converged with several common trends observed across countries and continents. These include reductions in dietary fiber, fruits, and vegetables, and increased intake of processed food, animal protein, fats, and sugary drinks, all of which have been linked epidemiologically to Crohn’s disease.

Treatment of Crohn’s disease and ulcerative colitis over the past 2 decades has focused on the immunologic dysfunction observed in these patients. Successful treatment has relied on suppressing immune responses either broadly or through targeted suppression of specific immunologic pathways. By and large, whereas these approaches have enabled us to make significant progress in reducing disease-related morbidity, success has been moderate at best, with fewer than half of patients in any clinical trial achieving remission at the end of a year. Thus, this approach alone may not be sufficient for most patients with IBD.

Treatment of IBD with diet was long considered out of the mainstream and confined to the realm of anecdotes and message boards. Despite most patients believing that diet played a role in development of IBD and onset of flares and that dietary modification was helpful in relieving symptoms, physicians – who for the most part were not trained in these approaches – were not believers, and probably rightly so in the absence of any supporting data.¹ However, the parallel emergence of three bodies of literature has now brought diet back into the mainstream of IBD care (such that not a single IBD conference goes by without at least a session or two on diet). First, large prospective cohorts from Europe and North America provided robust evidence linking long-term adult dietary patterns to disease incidence in adult-onset IBD, which supports many important case-control observations made over the past 2 decades.² Second, and perhaps most important, we began understanding the role of the microbiome in the development of these diseases and recognizing its centrality to bowel inflammation. One of the key determinants of the microbiome is diet, exerting both short-term and long-term influences on the microbial structure. While microbial changes are by no means the only mechanism through which diet can influence intestinal inflammation, they are among the most important, with broad effects across many dietary components. These findings provided a robust scientific basis for investigating the role of diet. Third, while still far from the high-quality (and expensive) set-up of investigational trials of pharmacologic therapies, dietary therapy studies have also evolved to randomized controlled trial designs and investigation of mechanism-driven dietary combinations. Together, I think these three recent advances, in addition to the wealth of existing literature and anecdotal experience, have been important in moving diet (back) into the IBD mainstream.

So what evidence is there that diet is effective in the treatment of IBD? Randomized controlled trials published more than a decade ago demonstrated that exclusive enteral nutrition, wherein all table foods are eliminated from a diet and the patient relies on an elemental diet alone for nutrition, was effective in not just inducing clinical remission but also improving inflammatory biomarkers.³ With results replicated in several trials, exclusive enteral nutrition is, in many parts of the world, one of the first-line treatments for pediatric Crohn’s disease. That this has not been translated to longer-term maintenance therapy is not necessarily an indicator of lack of durable efficacy, but reflects the challenges of maintaining such a restrictive diet long term while living an active, normal life. However, more recent rigorous studies have demonstrated that the effects of exclusive enteral nutrition can be mimicked either by a selected, less-restrictive diet (such as CD-TREAT⁴), which is more sustainable, or by combining partial enteral nutrition with an elimination diet that is quite diverse (such as CDED⁵). The latter two are considerably more promising as longer-term dietary treatments for Crohn’s disease with durable efficacy in open-label studies and randomized trials.

What are my final arguments for diet being used as a treatment for IBD? With the exception of very restrictive ones, diets are generally safe. Of course, patients on restricted diets need monitoring for nutritional deficiencies, but this monitoring is likely less intense than that needed for many of our immunosuppressive therapies. Dietary therapies are not associated with an increase in risk of infections or malignancy (unlike our traditional immunosuppressive therapies), and consequently are much more likely to be accepted by our patients than what we are currently offering. In addition, the existing treatments are expensive and consequently difficult to sustain globally with the increasing burden of these diseases. On the other hand, as eating and dietary choices are a routine part of day-to-day life, dietary therapies are not likely to be associated with any excess costs.

Therefore, treating IBD with diet alone is supported by epidemiologic, mechanistic, and clinical evidence and is a safe, effective, and inexpensive alternative for our patients.
 

References

1. Zallot C et al. Inflamm Bowel Dis. 2013 Jan;19(1):66-72.

2. Sasson AN et al. Clin Gastroenterol Hepatol. 2019 Dec 5;S1542-3565(19)31394-1.

3. Wall CL et al. World J Gastroenterol. 2013;19:7652-60.

4. Svolos V et al. Gastroenterology. 2019;156:1354-67.e6.

5. Levine A et al. Gastroenterology. 2019;157:440-50.e8.

Dr. Ananthakrishnan is a gastroenterologist in the division of gastroenterology, Crohn’s and Colitis Center, Massachusetts General Hospital and Harvard Medical School, Boston. He is supported by funding from the Crohn’s and Colitis Foundation and the Chleck Family Foundation.

IBD can be treated with diet alone – No, it cannot!

The cause of IBD is not completely understood, but we believe something in our environment triggers a dysregulated immune response in individuals with a genetic predisposition to IBD. Among the environmental triggers commonly recognized, diet is considered an important trigger through its ability to affect the composition and health of the gut microbiome and host barrier function. Epidemiologic data support this assumption. Westernization of diet has been associated with the increasing incidence of IBD across the globe and in immigrants who move from developing countries to an industrialized country. Observational studies have shown diets higher in meat and polyunsaturated fatty acids and omega-6 fatty acids are associated with a higher risk for IBD, whereas diets high in fruits, vegetables, and other sources of dietary fiber have a lower risk of IBD.

A growing body of evidence supports the impact food can have on gut health, specifically in mouse IBD models, but it is challenging to translate findings from animal studies into dietary interventions for IBD patients. Mouse studies help us understand the mechanistic basis of how diet may affect IBD, but randomized clinical trials establishing their role in IBD are lacking. This is not surprising as dietary studies are challenging, particularly if done in a robust manner, given the difficulties of ensuring and measuring dietary compliance.

Exclusive enteral nutrition (EEN) has been studied the most rigorously of all diets in IBD and has demonstrated the greatest benefit, compared with other diet studies in IBD. EEN requires the intake of elemental, semi-elemental, or polymeric formulas to meet all nutritional requirements without additional intake of food for 6-8 weeks. Studies have been performed mostly in pediatric populations and have shown effectiveness in induction of remission with reduction in inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, and even mucosal healing. EEN has not worked out as well for adult populations, because of the poor tolerability of exclusive intake of enteral formulas. Because of this limitation, studies of partial enteral nutrition have been performed that generally allow some food intake in addition to the enteral nutrition. When compared with EEN or anti–tumor necrosis factor–alpha therapy, partial enteral nutrition is a less-effective treatment of Crohn’s disease; however, partial enteral nutrition does appear to improve clinical symptoms.

Beyond EEN, there are many diets that have been considered for the treatment of IBD, including the specific carbohydrate diet (SCD), Crohn’s disease exclusion diet, autoimmune diet, low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols), Paleolithic diet, Mediterranean diet, and the semi-vegetarian diet, to name a few. Of these, only the SCD and Crohn’s disease exclusion diets have shown improvement in clinical remission and reduction in inflammatory markers.

The SCD diet is based on the theory that malabsorption of disaccharide and polysaccharide carbohydrates leads to bacterial overgrowth and host barrier dysfunction. This diet eliminates grains, dairy, processed meats, and certain vegetables such as potatoes, yams, and legumes. Small uncontrolled studies have shown improvement in symptoms and endoscopy findings. However, this restrictive diet is nearly impossible to follow long term. The Crohn’s disease exclusion diet is a whole foods diet avoiding all processed foods, animal fats, dairy, and gluten. Small studies of this diet have also shown improvement in clinical symptoms and inflammatory markers.

The plethora of studies and reports of the therapeutic effect of diet on IBD provide some promise of the benefit dietary modifications can bring to our IBD patients. However, most dietary studies are underpowered, lack a control arm, and do not include endoscopic endpoints. The current body of evidence remains insufficient to support the use of diet alone for the treatment of IBD. We need randomized clinical controlled trials that are held to the same rigor as those of our approved medical treatments for IBD. Although such trials are challenging, we’ve seen groups rise to the task to carry out more robust dietary studies in the IBD population, and we await the results of several ongoing trials.

IBD is a challenging disease to live with and often leaves our patients feeling out of control. Dietary choices provide an avenue for patients to have some control of their health. However, current evidence does not support the prescription of dietary interventions alone to treat IBD, particularly when we have known, effective therapies. While I am not ready to prescribe diet as a stand-alone treatment for IBD, I make a point to discuss the role diet may play in helping our patients achieve optimal health. As health care providers, it is our responsibility to provide holistic care to our patients, which includes promotion of a healthy diet, absent processed foods and added sugars. Healthy lifestyle choices combined with effective medical and surgical treatments offer our patients the best shot at sustained disease control.
 

References

1. Hou JK et al. Am J Gastroenterol. 2011;106(4):563-73.

2. Zachos M et al. Cochrane Database Syst Rev. 2007(1):CD000542.

3. Lee D et al. Inflamm Bowel Dis. 2015;21(8):1786-93.

4. Obih C et al. Nutrition. 2016;32(4):418-25.

5. Sigall Boneh R et al. J Crohns Colitis. 2017;11(10):1205-12.

Dr. Raffals is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. She has no financial conflicts of interest relevant to this paper.

Dear colleagues and friends,

Charles Kahi, MD, MS, AGAF, professor of medicine, Indiana University, Indianapolis. He is also an associate editor for GI & Hepatology News.

IBD can be treated with diet alone

Inflammatory bowel diseases (IBD), comprising Crohn’s disease and ulcerative colitis, have emerged as global diseases. The past 3 decades have seen a rising incidence of these diseases not just in the Western hemisphere, where their prevalence has been well recognized, but also in regions of the world such as Asia and South America where they were previously rare. Whereas several possible factors have been proposed to explain this rising incidence and globalization of disease with varying degrees of supportive evidence, one of the most likely factors is a changing diet. Over the same period that the disease incidence and prevalence have risen, diets worldwide have converged with several common trends observed across countries and continents. These include reductions in dietary fiber, fruits, and vegetables, and increased intake of processed food, animal protein, fats, and sugary drinks, all of which have been linked epidemiologically to Crohn’s disease.

Treatment of Crohn’s disease and ulcerative colitis over the past 2 decades has focused on the immunologic dysfunction observed in these patients. Successful treatment has relied on suppressing immune responses either broadly or through targeted suppression of specific immunologic pathways. By and large, whereas these approaches have enabled us to make significant progress in reducing disease-related morbidity, success has been moderate at best, with fewer than half of patients in any clinical trial achieving remission at the end of a year. Thus, this approach alone may not be sufficient for most patients with IBD.

Treatment of IBD with diet was long considered out of the mainstream and confined to the realm of anecdotes and message boards. Despite most patients believing that diet played a role in development of IBD and onset of flares and that dietary modification was helpful in relieving symptoms, physicians – who for the most part were not trained in these approaches – were not believers, and probably rightly so in the absence of any supporting data.¹ However, the parallel emergence of three bodies of literature has now brought diet back into the mainstream of IBD care (such that not a single IBD conference goes by without at least a session or two on diet). First, large prospective cohorts from Europe and North America provided robust evidence linking long-term adult dietary patterns to disease incidence in adult-onset IBD, which supports many important case-control observations made over the past 2 decades.² Second, and perhaps most important, we began understanding the role of the microbiome in the development of these diseases and recognizing its centrality to bowel inflammation. One of the key determinants of the microbiome is diet, exerting both short-term and long-term influences on the microbial structure. While microbial changes are by no means the only mechanism through which diet can influence intestinal inflammation, they are among the most important, with broad effects across many dietary components. These findings provided a robust scientific basis for investigating the role of diet. Third, while still far from the high-quality (and expensive) set-up of investigational trials of pharmacologic therapies, dietary therapy studies have also evolved to randomized controlled trial designs and investigation of mechanism-driven dietary combinations. Together, I think these three recent advances, in addition to the wealth of existing literature and anecdotal experience, have been important in moving diet (back) into the IBD mainstream.

So what evidence is there that diet is effective in the treatment of IBD? Randomized controlled trials published more than a decade ago demonstrated that exclusive enteral nutrition, wherein all table foods are eliminated from a diet and the patient relies on an elemental diet alone for nutrition, was effective in not just inducing clinical remission but also improving inflammatory biomarkers.³ With results replicated in several trials, exclusive enteral nutrition is, in many parts of the world, one of the first-line treatments for pediatric Crohn’s disease. That this has not been translated to longer-term maintenance therapy is not necessarily an indicator of lack of durable efficacy, but reflects the challenges of maintaining such a restrictive diet long term while living an active, normal life. However, more recent rigorous studies have demonstrated that the effects of exclusive enteral nutrition can be mimicked either by a selected, less-restrictive diet (such as CD-TREAT⁴), which is more sustainable, or by combining partial enteral nutrition with an elimination diet that is quite diverse (such as CDED⁵). The latter two are considerably more promising as longer-term dietary treatments for Crohn’s disease with durable efficacy in open-label studies and randomized trials.

What are my final arguments for diet being used as a treatment for IBD? With the exception of very restrictive ones, diets are generally safe. Of course, patients on restricted diets need monitoring for nutritional deficiencies, but this monitoring is likely less intense than that needed for many of our immunosuppressive therapies. Dietary therapies are not associated with an increase in risk of infections or malignancy (unlike our traditional immunosuppressive therapies), and consequently are much more likely to be accepted by our patients than what we are currently offering. In addition, the existing treatments are expensive and consequently difficult to sustain globally with the increasing burden of these diseases. On the other hand, as eating and dietary choices are a routine part of day-to-day life, dietary therapies are not likely to be associated with any excess costs.

Therefore, treating IBD with diet alone is supported by epidemiologic, mechanistic, and clinical evidence and is a safe, effective, and inexpensive alternative for our patients.
 

References

1. Zallot C et al. Inflamm Bowel Dis. 2013 Jan;19(1):66-72.

2. Sasson AN et al. Clin Gastroenterol Hepatol. 2019 Dec 5;S1542-3565(19)31394-1.

3. Wall CL et al. World J Gastroenterol. 2013;19:7652-60.

4. Svolos V et al. Gastroenterology. 2019;156:1354-67.e6.

5. Levine A et al. Gastroenterology. 2019;157:440-50.e8.

Dr. Ananthakrishnan is a gastroenterologist in the division of gastroenterology, Crohn’s and Colitis Center, Massachusetts General Hospital and Harvard Medical School, Boston. He is supported by funding from the Crohn’s and Colitis Foundation and the Chleck Family Foundation.

IBD can be treated with diet alone – No, it cannot!

The cause of IBD is not completely understood, but we believe something in our environment triggers a dysregulated immune response in individuals with a genetic predisposition to IBD. Among the environmental triggers commonly recognized, diet is considered an important trigger through its ability to affect the composition and health of the gut microbiome and host barrier function. Epidemiologic data support this assumption. Westernization of diet has been associated with the increasing incidence of IBD across the globe and in immigrants who move from developing countries to an industrialized country. Observational studies have shown diets higher in meat and polyunsaturated fatty acids and omega-6 fatty acids are associated with a higher risk for IBD, whereas diets high in fruits, vegetables, and other sources of dietary fiber have a lower risk of IBD.

A growing body of evidence supports the impact food can have on gut health, specifically in mouse IBD models, but it is challenging to translate findings from animal studies into dietary interventions for IBD patients. Mouse studies help us understand the mechanistic basis of how diet may affect IBD, but randomized clinical trials establishing their role in IBD are lacking. This is not surprising as dietary studies are challenging, particularly if done in a robust manner, given the difficulties of ensuring and measuring dietary compliance.

Exclusive enteral nutrition (EEN) has been studied the most rigorously of all diets in IBD and has demonstrated the greatest benefit, compared with other diet studies in IBD. EEN requires the intake of elemental, semi-elemental, or polymeric formulas to meet all nutritional requirements without additional intake of food for 6-8 weeks. Studies have been performed mostly in pediatric populations and have shown effectiveness in induction of remission with reduction in inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin, and even mucosal healing. EEN has not worked out as well for adult populations, because of the poor tolerability of exclusive intake of enteral formulas. Because of this limitation, studies of partial enteral nutrition have been performed that generally allow some food intake in addition to the enteral nutrition. When compared with EEN or anti–tumor necrosis factor–alpha therapy, partial enteral nutrition is a less-effective treatment of Crohn’s disease; however, partial enteral nutrition does appear to improve clinical symptoms.

Beyond EEN, there are many diets that have been considered for the treatment of IBD, including the specific carbohydrate diet (SCD), Crohn’s disease exclusion diet, autoimmune diet, low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols), Paleolithic diet, Mediterranean diet, and the semi-vegetarian diet, to name a few. Of these, only the SCD and Crohn’s disease exclusion diets have shown improvement in clinical remission and reduction in inflammatory markers.

The SCD diet is based on the theory that malabsorption of disaccharide and polysaccharide carbohydrates leads to bacterial overgrowth and host barrier dysfunction. This diet eliminates grains, dairy, processed meats, and certain vegetables such as potatoes, yams, and legumes. Small uncontrolled studies have shown improvement in symptoms and endoscopy findings. However, this restrictive diet is nearly impossible to follow long term. The Crohn’s disease exclusion diet is a whole foods diet avoiding all processed foods, animal fats, dairy, and gluten. Small studies of this diet have also shown improvement in clinical symptoms and inflammatory markers.

The plethora of studies and reports of the therapeutic effect of diet on IBD provide some promise of the benefit dietary modifications can bring to our IBD patients. However, most dietary studies are underpowered, lack a control arm, and do not include endoscopic endpoints. The current body of evidence remains insufficient to support the use of diet alone for the treatment of IBD. We need randomized clinical controlled trials that are held to the same rigor as those of our approved medical treatments for IBD. Although such trials are challenging, we’ve seen groups rise to the task to carry out more robust dietary studies in the IBD population, and we await the results of several ongoing trials.

IBD is a challenging disease to live with and often leaves our patients feeling out of control. Dietary choices provide an avenue for patients to have some control of their health. However, current evidence does not support the prescription of dietary interventions alone to treat IBD, particularly when we have known, effective therapies. While I am not ready to prescribe diet as a stand-alone treatment for IBD, I make a point to discuss the role diet may play in helping our patients achieve optimal health. As health care providers, it is our responsibility to provide holistic care to our patients, which includes promotion of a healthy diet, absent processed foods and added sugars. Healthy lifestyle choices combined with effective medical and surgical treatments offer our patients the best shot at sustained disease control.
 

References

1. Hou JK et al. Am J Gastroenterol. 2011;106(4):563-73.

2. Zachos M et al. Cochrane Database Syst Rev. 2007(1):CD000542.

3. Lee D et al. Inflamm Bowel Dis. 2015;21(8):1786-93.

4. Obih C et al. Nutrition. 2016;32(4):418-25.

5. Sigall Boneh R et al. J Crohns Colitis. 2017;11(10):1205-12.

Dr. Raffals is a gastroenterologist in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. She has no financial conflicts of interest relevant to this paper.

Between 23,000 and 46,000 U.S. children live with chronic hepatitis C virus with a prevalence of 0.17% anti–hepatitis C virus (HCV) antibody positivity in those aged 6-11 years and 0.39% among children aged 12-19 years. In the United States, genotype 1 is most frequent, followed by genotypes 2 and 3. About 99% of cases result from vertical transmission; transfusion-related cases have not been observed in recent decades.Only viremic mothers are at risk of transmission as those who have spontaneously cleared HCV viremia or have been treated successfully do not risk transmission. Maternal HCV viral load appears to be a risk factor for HCV transmission, however transmission is reported at all levels of viremia.

In conjunction with the opioid epidemics, the prevalence of HCV infection has increased over the last decade. The Centers for Disease Control and Prevention reported that, between 2009 and 2014, the prevalence of HCV infection increased from 1.8 to 3.4 per 1,000 live births. They identified substantial state-to-state variation with the highest rate in West Virginia (22.6 per 1,000 live births), and the lowest in Hawaii (0.7 per 1,000 live births). The implications are clear that increasing numbers of newborns are exposed to HCV and, if transmission rates are between 1% and 5%, 80-400 U.S. infants each year acquire HCV infection.
 

HCV in children

HCV in children is almost always associated with persistent transaminitis. Chronic infection is defined as the persistence of HCV RNA for at least 6 months, and clearance of HCV infection is determined by the persistent disappearance of HCV RNA. Regardless of infection status, an infant may have detectable maternal anti-HCV antibody in serum until 18 months of age, resulting from passive transfer. In addition, prolonged infection can lead to cirrhosis, hepatocellular carcinoma, or decompensated liver disease. Potential extrahepatic manifestations including reduced physical and psychosocial health also are linked to chronic HCV. Autoimmune disease also has been reported in children with HCV. As well, the stigma of HCV elicits fear in school and child care settings that is a result of public misunderstanding regarding routes of hepatitis C transmission. No restriction of regular childhood activities is required in the daily life of HCV-infected children.

Taken together, increasing rates of HCV infection in pregnant women, increasing numbers of exposed and infected infants annually, potential for both short- and long-term morbidity, and curative nontoxic treatment, the paradigm for early identification and treatment at age 3 years is changing.
 

Screening for HCV

There is considerable discussion about which strategy for screening of at-risk infants is more appropriate. Some groups advocate for HCV-RNA testing within the first year of life. Proponents argue the use of a highly sensitive RNA assay early in life has potential to increase detection of infected infants while a negative result allows the conclusion the infant is not infected. Advocates hypothesize that early identification has potential to improve continued follow-up.

Opponents argue that early testing does not change the need for repeat testing after 18 months to confirm diagnosis. They also argue that HCV RNA is more expensive than an antibody-based testing; and treatment will not begin prior to age 3 as there is still opportunity for viremia to spontaneously clear.
 

Direct acting agents licensed

Ledipasvir/sofosbuvir (Harvoni) was initially demonstrated as curative for genotype 1, 4, 5, or 6 infection in a phase 2, multicenter, open-label study of 100 adolescents with genotype 1 treated for 12 weeks. Sustained virologic response (SVR) was documented in 98% of participants.The regimen was safe and well tolerated in this population, and the adult dosage formulation resulted in pharmacokinetic characteristics similar to those observed in adults. Two clinical trials supported the efficacy of ledipasvir/sofosbuvir in the pediatric population aged 3-11 years. This regimen also is recommended for interferon-experienced (± ribavirin, with or without an HCV protease inhibitor) children and adolescents aged 3 years or older with genotype 1 or 4. A 12-week course is recommended for patients without cirrhosis; 24 weeks is recommended for those with compensated cirrhosis. The combination of ledipasvir/sofosbuvir is the only treatment option for children aged 3-6 years with genotype 1, 4, 5, or 6 infection.

The efficacy of sofosbuvir/velpatasvir (Epclusa) once daily for 12 weeks was first evaluated in an open-label trial among children aged 6 years and older with genotype 1, 2, 3, 4, or 6 infection, without cirrhosis or with compensated cirrhosis. Subsequently, the “cocktail” was evaluated in children aged 6-12 years, with 76% genotype 1, 3% genotype 2, 15% genotype 3, and 6% genotype 4. SVR12 rates were 93% (50/54) in children with genotype 1, 91% (10/11) in those with genotype 3, and 100% in participants with genotype 2 (2/2) or genotype 4 (4/4). Sofosbuvir/velpatasvir was approved in March 2020 by the Food and Drug Administration for pediatric patients aged 6 years and older. Given its pangenotypic activity, safety, and efficacy, sofosbuvir/velpatasvir is currently recommended as a first choice for HCV treatment in children and adolescents aged at least 6 years.

The daily fixed-dose combination of glecaprevir/pibrentasvir (Mavyret) was approved in April 2019 for adolescents aged 12-17 years, and weighing at least 45 kg.Treatment is for 8 weeks, and includes treatment-naive patients without cirrhosis or those with compensated cirrhosis. SVR12 rates for Mavyret have ranged from 91% to 100 % across clinic trials. FDA approval and HCV guideline treatment recommendations for direct-acting antiviral (DAA)–experienced adolescents are based on clinical trial data from adults. Given its pangenotypic activity, safety, and efficacy record in adult patients, glecaprevir/pibrentasvir is recommended as a first choice for adolescent HCV treatment. Glecaprevir/pibrentasvir once approved for children less than 3 years of age will be safe and efficacious as a pangenotypic treatment option in children with chronic HCV infection.
 

Current recommendations

Tools for identifying HCV infected infants as early as a few months of age are available, yet studies demonstrate that a minority of at-risk children are tested for HCV using either an HCV polymerase chain reaction strategy early in life or an anti-HCV antibody strategy after 18 months of age.

Therapy with direct-acting agents is now licensed to those aged 3 years and offers the potential for cure, eliminating concern for possible progression after prolonged infection. Such therapy offers the potential to eliminate the stigma faced by many children as well as the hepatic and extrahepatic manifestations observed in children. Medication formulation and the child’s abilities to take the medication needs to be considered when prescribing DAAs. It is important to assess if the child can successfully swallow pills. Currently, Harvoni is the only medication that comes in both pellet and pill formulations. The dose is based on weight. The pellets need to be given in a small amount of nonacidic food; they cannot be chewed.

All children with chronic HCV infection are candidates for treatment. When significant fibrosis and/or cirrhosis is present treatment should not be delayed once the child is age 3 years; when only transaminitis is present, treatment can be delayed. In our experience, parents are eager to complete treatment before starting kindergarten.

Liver biopsy for obtaining liver tissue for histopathologic examination is not routinely indicated in children with chronic HCV infection but should be evaluated case by case. Noninvasive tests of hepatic fibrosis have been used in children, these include serologic markers (i.e., FibroSure) and radiologic tests such as ultrasound-based transient elastography (i.e., Fibroscan). Validation for pediatric patients is variable for the different serologic tests. Studies have shown that Fibroscan using the M probe is feasible for a wide range of ages, but poor patient cooperation may make measurement difficult.

Further details regarding dosing and choice of formulation is available at https://www.hcvguidelines.org/unique-populations/children.

Dr. Sabharwal is assistant professor of pediatrics at Boston University and attending physician in pediatric infectious diseases at Boston Medical Center. Ms. Moloney is an instructor in pediatrics at Boston University and a pediatric nurse practitioner in pediatric infectious diseases at Boston Medicine Center. Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician at Boston Medical Center. Boston Medical Center received funding from AbbVie for study of Harvoni in Children 3 years of age and older. Email them at pdnews@mdedge.com.

References

MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):470-3. Hepatol Commun. 2017 March 23. doi: 10.1002/hep4.1028. Hepatology. 2020 Feb;71(2):422-30. Lancet Gastroenterol Hepatol. 2019 Apr 11. doi: 10.1016/S2468-1253(19)30046-9. Arch Dis Child. 2006 Sep;91(9):781-5. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):123-31.

Between 23,000 and 46,000 U.S. children live with chronic hepatitis C virus with a prevalence of 0.17% anti–hepatitis C virus (HCV) antibody positivity in those aged 6-11 years and 0.39% among children aged 12-19 years. In the United States, genotype 1 is most frequent, followed by genotypes 2 and 3. About 99% of cases result from vertical transmission; transfusion-related cases have not been observed in recent decades.Only viremic mothers are at risk of transmission as those who have spontaneously cleared HCV viremia or have been treated successfully do not risk transmission. Maternal HCV viral load appears to be a risk factor for HCV transmission, however transmission is reported at all levels of viremia.

In conjunction with the opioid epidemics, the prevalence of HCV infection has increased over the last decade. The Centers for Disease Control and Prevention reported that, between 2009 and 2014, the prevalence of HCV infection increased from 1.8 to 3.4 per 1,000 live births. They identified substantial state-to-state variation with the highest rate in West Virginia (22.6 per 1,000 live births), and the lowest in Hawaii (0.7 per 1,000 live births). The implications are clear that increasing numbers of newborns are exposed to HCV and, if transmission rates are between 1% and 5%, 80-400 U.S. infants each year acquire HCV infection.
 

HCV in children

HCV in children is almost always associated with persistent transaminitis. Chronic infection is defined as the persistence of HCV RNA for at least 6 months, and clearance of HCV infection is determined by the persistent disappearance of HCV RNA. Regardless of infection status, an infant may have detectable maternal anti-HCV antibody in serum until 18 months of age, resulting from passive transfer. In addition, prolonged infection can lead to cirrhosis, hepatocellular carcinoma, or decompensated liver disease. Potential extrahepatic manifestations including reduced physical and psychosocial health also are linked to chronic HCV. Autoimmune disease also has been reported in children with HCV. As well, the stigma of HCV elicits fear in school and child care settings that is a result of public misunderstanding regarding routes of hepatitis C transmission. No restriction of regular childhood activities is required in the daily life of HCV-infected children.

Taken together, increasing rates of HCV infection in pregnant women, increasing numbers of exposed and infected infants annually, potential for both short- and long-term morbidity, and curative nontoxic treatment, the paradigm for early identification and treatment at age 3 years is changing.
 

Screening for HCV

There is considerable discussion about which strategy for screening of at-risk infants is more appropriate. Some groups advocate for HCV-RNA testing within the first year of life. Proponents argue the use of a highly sensitive RNA assay early in life has potential to increase detection of infected infants while a negative result allows the conclusion the infant is not infected. Advocates hypothesize that early identification has potential to improve continued follow-up.

Opponents argue that early testing does not change the need for repeat testing after 18 months to confirm diagnosis. They also argue that HCV RNA is more expensive than an antibody-based testing; and treatment will not begin prior to age 3 as there is still opportunity for viremia to spontaneously clear.
 

Direct acting agents licensed

Ledipasvir/sofosbuvir (Harvoni) was initially demonstrated as curative for genotype 1, 4, 5, or 6 infection in a phase 2, multicenter, open-label study of 100 adolescents with genotype 1 treated for 12 weeks. Sustained virologic response (SVR) was documented in 98% of participants.The regimen was safe and well tolerated in this population, and the adult dosage formulation resulted in pharmacokinetic characteristics similar to those observed in adults. Two clinical trials supported the efficacy of ledipasvir/sofosbuvir in the pediatric population aged 3-11 years. This regimen also is recommended for interferon-experienced (± ribavirin, with or without an HCV protease inhibitor) children and adolescents aged 3 years or older with genotype 1 or 4. A 12-week course is recommended for patients without cirrhosis; 24 weeks is recommended for those with compensated cirrhosis. The combination of ledipasvir/sofosbuvir is the only treatment option for children aged 3-6 years with genotype 1, 4, 5, or 6 infection.

The efficacy of sofosbuvir/velpatasvir (Epclusa) once daily for 12 weeks was first evaluated in an open-label trial among children aged 6 years and older with genotype 1, 2, 3, 4, or 6 infection, without cirrhosis or with compensated cirrhosis. Subsequently, the “cocktail” was evaluated in children aged 6-12 years, with 76% genotype 1, 3% genotype 2, 15% genotype 3, and 6% genotype 4. SVR12 rates were 93% (50/54) in children with genotype 1, 91% (10/11) in those with genotype 3, and 100% in participants with genotype 2 (2/2) or genotype 4 (4/4). Sofosbuvir/velpatasvir was approved in March 2020 by the Food and Drug Administration for pediatric patients aged 6 years and older. Given its pangenotypic activity, safety, and efficacy, sofosbuvir/velpatasvir is currently recommended as a first choice for HCV treatment in children and adolescents aged at least 6 years.

The daily fixed-dose combination of glecaprevir/pibrentasvir (Mavyret) was approved in April 2019 for adolescents aged 12-17 years, and weighing at least 45 kg.Treatment is for 8 weeks, and includes treatment-naive patients without cirrhosis or those with compensated cirrhosis. SVR12 rates for Mavyret have ranged from 91% to 100 % across clinic trials. FDA approval and HCV guideline treatment recommendations for direct-acting antiviral (DAA)–experienced adolescents are based on clinical trial data from adults. Given its pangenotypic activity, safety, and efficacy record in adult patients, glecaprevir/pibrentasvir is recommended as a first choice for adolescent HCV treatment. Glecaprevir/pibrentasvir once approved for children less than 3 years of age will be safe and efficacious as a pangenotypic treatment option in children with chronic HCV infection.
 

Current recommendations

Tools for identifying HCV infected infants as early as a few months of age are available, yet studies demonstrate that a minority of at-risk children are tested for HCV using either an HCV polymerase chain reaction strategy early in life or an anti-HCV antibody strategy after 18 months of age.

Therapy with direct-acting agents is now licensed to those aged 3 years and offers the potential for cure, eliminating concern for possible progression after prolonged infection. Such therapy offers the potential to eliminate the stigma faced by many children as well as the hepatic and extrahepatic manifestations observed in children. Medication formulation and the child’s abilities to take the medication needs to be considered when prescribing DAAs. It is important to assess if the child can successfully swallow pills. Currently, Harvoni is the only medication that comes in both pellet and pill formulations. The dose is based on weight. The pellets need to be given in a small amount of nonacidic food; they cannot be chewed.

All children with chronic HCV infection are candidates for treatment. When significant fibrosis and/or cirrhosis is present treatment should not be delayed once the child is age 3 years; when only transaminitis is present, treatment can be delayed. In our experience, parents are eager to complete treatment before starting kindergarten.

Liver biopsy for obtaining liver tissue for histopathologic examination is not routinely indicated in children with chronic HCV infection but should be evaluated case by case. Noninvasive tests of hepatic fibrosis have been used in children, these include serologic markers (i.e., FibroSure) and radiologic tests such as ultrasound-based transient elastography (i.e., Fibroscan). Validation for pediatric patients is variable for the different serologic tests. Studies have shown that Fibroscan using the M probe is feasible for a wide range of ages, but poor patient cooperation may make measurement difficult.

Further details regarding dosing and choice of formulation is available at https://www.hcvguidelines.org/unique-populations/children.

Dr. Sabharwal is assistant professor of pediatrics at Boston University and attending physician in pediatric infectious diseases at Boston Medical Center. Ms. Moloney is an instructor in pediatrics at Boston University and a pediatric nurse practitioner in pediatric infectious diseases at Boston Medicine Center. Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician at Boston Medical Center. Boston Medical Center received funding from AbbVie for study of Harvoni in Children 3 years of age and older. Email them at pdnews@mdedge.com.

References

MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):470-3. Hepatol Commun. 2017 March 23. doi: 10.1002/hep4.1028. Hepatology. 2020 Feb;71(2):422-30. Lancet Gastroenterol Hepatol. 2019 Apr 11. doi: 10.1016/S2468-1253(19)30046-9. Arch Dis Child. 2006 Sep;91(9):781-5. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):123-31.

Between 23,000 and 46,000 U.S. children live with chronic hepatitis C virus with a prevalence of 0.17% anti–hepatitis C virus (HCV) antibody positivity in those aged 6-11 years and 0.39% among children aged 12-19 years. In the United States, genotype 1 is most frequent, followed by genotypes 2 and 3. About 99% of cases result from vertical transmission; transfusion-related cases have not been observed in recent decades.Only viremic mothers are at risk of transmission as those who have spontaneously cleared HCV viremia or have been treated successfully do not risk transmission. Maternal HCV viral load appears to be a risk factor for HCV transmission, however transmission is reported at all levels of viremia.

In conjunction with the opioid epidemics, the prevalence of HCV infection has increased over the last decade. The Centers for Disease Control and Prevention reported that, between 2009 and 2014, the prevalence of HCV infection increased from 1.8 to 3.4 per 1,000 live births. They identified substantial state-to-state variation with the highest rate in West Virginia (22.6 per 1,000 live births), and the lowest in Hawaii (0.7 per 1,000 live births). The implications are clear that increasing numbers of newborns are exposed to HCV and, if transmission rates are between 1% and 5%, 80-400 U.S. infants each year acquire HCV infection.
 

HCV in children

HCV in children is almost always associated with persistent transaminitis. Chronic infection is defined as the persistence of HCV RNA for at least 6 months, and clearance of HCV infection is determined by the persistent disappearance of HCV RNA. Regardless of infection status, an infant may have detectable maternal anti-HCV antibody in serum until 18 months of age, resulting from passive transfer. In addition, prolonged infection can lead to cirrhosis, hepatocellular carcinoma, or decompensated liver disease. Potential extrahepatic manifestations including reduced physical and psychosocial health also are linked to chronic HCV. Autoimmune disease also has been reported in children with HCV. As well, the stigma of HCV elicits fear in school and child care settings that is a result of public misunderstanding regarding routes of hepatitis C transmission. No restriction of regular childhood activities is required in the daily life of HCV-infected children.

Taken together, increasing rates of HCV infection in pregnant women, increasing numbers of exposed and infected infants annually, potential for both short- and long-term morbidity, and curative nontoxic treatment, the paradigm for early identification and treatment at age 3 years is changing.
 

Screening for HCV

There is considerable discussion about which strategy for screening of at-risk infants is more appropriate. Some groups advocate for HCV-RNA testing within the first year of life. Proponents argue the use of a highly sensitive RNA assay early in life has potential to increase detection of infected infants while a negative result allows the conclusion the infant is not infected. Advocates hypothesize that early identification has potential to improve continued follow-up.

Opponents argue that early testing does not change the need for repeat testing after 18 months to confirm diagnosis. They also argue that HCV RNA is more expensive than an antibody-based testing; and treatment will not begin prior to age 3 as there is still opportunity for viremia to spontaneously clear.
 

Direct acting agents licensed

Ledipasvir/sofosbuvir (Harvoni) was initially demonstrated as curative for genotype 1, 4, 5, or 6 infection in a phase 2, multicenter, open-label study of 100 adolescents with genotype 1 treated for 12 weeks. Sustained virologic response (SVR) was documented in 98% of participants.The regimen was safe and well tolerated in this population, and the adult dosage formulation resulted in pharmacokinetic characteristics similar to those observed in adults. Two clinical trials supported the efficacy of ledipasvir/sofosbuvir in the pediatric population aged 3-11 years. This regimen also is recommended for interferon-experienced (± ribavirin, with or without an HCV protease inhibitor) children and adolescents aged 3 years or older with genotype 1 or 4. A 12-week course is recommended for patients without cirrhosis; 24 weeks is recommended for those with compensated cirrhosis. The combination of ledipasvir/sofosbuvir is the only treatment option for children aged 3-6 years with genotype 1, 4, 5, or 6 infection.

The efficacy of sofosbuvir/velpatasvir (Epclusa) once daily for 12 weeks was first evaluated in an open-label trial among children aged 6 years and older with genotype 1, 2, 3, 4, or 6 infection, without cirrhosis or with compensated cirrhosis. Subsequently, the “cocktail” was evaluated in children aged 6-12 years, with 76% genotype 1, 3% genotype 2, 15% genotype 3, and 6% genotype 4. SVR12 rates were 93% (50/54) in children with genotype 1, 91% (10/11) in those with genotype 3, and 100% in participants with genotype 2 (2/2) or genotype 4 (4/4). Sofosbuvir/velpatasvir was approved in March 2020 by the Food and Drug Administration for pediatric patients aged 6 years and older. Given its pangenotypic activity, safety, and efficacy, sofosbuvir/velpatasvir is currently recommended as a first choice for HCV treatment in children and adolescents aged at least 6 years.

The daily fixed-dose combination of glecaprevir/pibrentasvir (Mavyret) was approved in April 2019 for adolescents aged 12-17 years, and weighing at least 45 kg.Treatment is for 8 weeks, and includes treatment-naive patients without cirrhosis or those with compensated cirrhosis. SVR12 rates for Mavyret have ranged from 91% to 100 % across clinic trials. FDA approval and HCV guideline treatment recommendations for direct-acting antiviral (DAA)–experienced adolescents are based on clinical trial data from adults. Given its pangenotypic activity, safety, and efficacy record in adult patients, glecaprevir/pibrentasvir is recommended as a first choice for adolescent HCV treatment. Glecaprevir/pibrentasvir once approved for children less than 3 years of age will be safe and efficacious as a pangenotypic treatment option in children with chronic HCV infection.
 

Current recommendations

Tools for identifying HCV infected infants as early as a few months of age are available, yet studies demonstrate that a minority of at-risk children are tested for HCV using either an HCV polymerase chain reaction strategy early in life or an anti-HCV antibody strategy after 18 months of age.

Therapy with direct-acting agents is now licensed to those aged 3 years and offers the potential for cure, eliminating concern for possible progression after prolonged infection. Such therapy offers the potential to eliminate the stigma faced by many children as well as the hepatic and extrahepatic manifestations observed in children. Medication formulation and the child’s abilities to take the medication needs to be considered when prescribing DAAs. It is important to assess if the child can successfully swallow pills. Currently, Harvoni is the only medication that comes in both pellet and pill formulations. The dose is based on weight. The pellets need to be given in a small amount of nonacidic food; they cannot be chewed.

All children with chronic HCV infection are candidates for treatment. When significant fibrosis and/or cirrhosis is present treatment should not be delayed once the child is age 3 years; when only transaminitis is present, treatment can be delayed. In our experience, parents are eager to complete treatment before starting kindergarten.

Liver biopsy for obtaining liver tissue for histopathologic examination is not routinely indicated in children with chronic HCV infection but should be evaluated case by case. Noninvasive tests of hepatic fibrosis have been used in children, these include serologic markers (i.e., FibroSure) and radiologic tests such as ultrasound-based transient elastography (i.e., Fibroscan). Validation for pediatric patients is variable for the different serologic tests. Studies have shown that Fibroscan using the M probe is feasible for a wide range of ages, but poor patient cooperation may make measurement difficult.

Further details regarding dosing and choice of formulation is available at https://www.hcvguidelines.org/unique-populations/children.

Dr. Sabharwal is assistant professor of pediatrics at Boston University and attending physician in pediatric infectious diseases at Boston Medical Center. Ms. Moloney is an instructor in pediatrics at Boston University and a pediatric nurse practitioner in pediatric infectious diseases at Boston Medicine Center. Dr. Pelton is professor of pediatrics and epidemiology at Boston University and public health and senior attending physician at Boston Medical Center. Boston Medical Center received funding from AbbVie for study of Harvoni in Children 3 years of age and older. Email them at pdnews@mdedge.com.

References

MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):470-3. Hepatol Commun. 2017 March 23. doi: 10.1002/hep4.1028. Hepatology. 2020 Feb;71(2):422-30. Lancet Gastroenterol Hepatol. 2019 Apr 11. doi: 10.1016/S2468-1253(19)30046-9. Arch Dis Child. 2006 Sep;91(9):781-5. J Pediatr Gastroenterol Nutr. 2010 Feb;50(2):123-31.