Background: A previous study has shown that patients with acute COPD exacerbations had little difference in rate of clinical cure with placebo or antibiotics when CRP is less than 40 mg/L.

Setting: 86 general medical practices in the United Kingdom from January 2015 through September 2017.

Synopsis: More than 600 patients who presented to a primary care physician with an acute COPD exacerbation were randomized to point of care CRP testing vs. usual care. Clinicians in the CRP testing group were provided with a point-of-care testing unit along with an algorithm for results. If the CRP was greater than 40 mg/L, antibiotics were thought to be beneficial; but they were urged not to prescribe antibiotics if the level was less than 20 mg/L. For levels between 20 mg/L and 40 mg/L, it was suggested that antibiotics might be beneficial if the sputum is purulent.

The primary outcomes were patient-reported use of antibiotics for an acute COPD exacerbation within 4 weeks of randomization along with measurement of COPD-related health status on the Clinical COPD Questionnaire at 2 weeks of randomization. Fewer antibiotics were prescribed in the CRP testing group over the usual care group (57% vs. 77%). The adjusted mean difference in the Clinical COPD Questionnaire total score at 2 weeks was –0.19 points, in favor of the CRP-guided group.

Bottom line: The use of point-of-care testing CRP as an adjunctive guide to antibiotic use in acute COPD exacerbations may lower the amount of antibiotic prescribing without compromising clinical outcomes.

Citation: Butler CC et al. C-reactive protein testing to guide antibiotics prescribing for COPD exacerbations. N Engl J Med. 2019 Jul 11; 381:111-120.

Dr. Choksi is a hospitalist and associate professor of internal medicine at Saint Louis University, where she is assistant dean of admissions. She is president of the SHM St. Louis Chapter.

Background: A previous study has shown that patients with acute COPD exacerbations had little difference in rate of clinical cure with placebo or antibiotics when CRP is less than 40 mg/L.

Setting: 86 general medical practices in the United Kingdom from January 2015 through September 2017.

Synopsis: More than 600 patients who presented to a primary care physician with an acute COPD exacerbation were randomized to point of care CRP testing vs. usual care. Clinicians in the CRP testing group were provided with a point-of-care testing unit along with an algorithm for results. If the CRP was greater than 40 mg/L, antibiotics were thought to be beneficial; but they were urged not to prescribe antibiotics if the level was less than 20 mg/L. For levels between 20 mg/L and 40 mg/L, it was suggested that antibiotics might be beneficial if the sputum is purulent.

The primary outcomes were patient-reported use of antibiotics for an acute COPD exacerbation within 4 weeks of randomization along with measurement of COPD-related health status on the Clinical COPD Questionnaire at 2 weeks of randomization. Fewer antibiotics were prescribed in the CRP testing group over the usual care group (57% vs. 77%). The adjusted mean difference in the Clinical COPD Questionnaire total score at 2 weeks was –0.19 points, in favor of the CRP-guided group.

Bottom line: The use of point-of-care testing CRP as an adjunctive guide to antibiotic use in acute COPD exacerbations may lower the amount of antibiotic prescribing without compromising clinical outcomes.

Citation: Butler CC et al. C-reactive protein testing to guide antibiotics prescribing for COPD exacerbations. N Engl J Med. 2019 Jul 11; 381:111-120.

Dr. Choksi is a hospitalist and associate professor of internal medicine at Saint Louis University, where she is assistant dean of admissions. She is president of the SHM St. Louis Chapter.

Background: A previous study has shown that patients with acute COPD exacerbations had little difference in rate of clinical cure with placebo or antibiotics when CRP is less than 40 mg/L.

Setting: 86 general medical practices in the United Kingdom from January 2015 through September 2017.

Synopsis: More than 600 patients who presented to a primary care physician with an acute COPD exacerbation were randomized to point of care CRP testing vs. usual care. Clinicians in the CRP testing group were provided with a point-of-care testing unit along with an algorithm for results. If the CRP was greater than 40 mg/L, antibiotics were thought to be beneficial; but they were urged not to prescribe antibiotics if the level was less than 20 mg/L. For levels between 20 mg/L and 40 mg/L, it was suggested that antibiotics might be beneficial if the sputum is purulent.

The primary outcomes were patient-reported use of antibiotics for an acute COPD exacerbation within 4 weeks of randomization along with measurement of COPD-related health status on the Clinical COPD Questionnaire at 2 weeks of randomization. Fewer antibiotics were prescribed in the CRP testing group over the usual care group (57% vs. 77%). The adjusted mean difference in the Clinical COPD Questionnaire total score at 2 weeks was –0.19 points, in favor of the CRP-guided group.

Bottom line: The use of point-of-care testing CRP as an adjunctive guide to antibiotic use in acute COPD exacerbations may lower the amount of antibiotic prescribing without compromising clinical outcomes.

Citation: Butler CC et al. C-reactive protein testing to guide antibiotics prescribing for COPD exacerbations. N Engl J Med. 2019 Jul 11; 381:111-120.

Dr. Choksi is a hospitalist and associate professor of internal medicine at Saint Louis University, where she is assistant dean of admissions. She is president of the SHM St. Louis Chapter.

As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).

While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.

However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
 

1. Participation in the vaccine trials by minority populations

With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.¹ Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.

Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.² Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.³

The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.

In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.

Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.

While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
 

2. Equitable allocation and distribution of vaccine for minority populations

Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.

The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
 

3. Immunization uptake by minority populations

Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.

According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.³ This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.^4-9

On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.¹⁰ Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.

When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.¹¹ It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.¹² Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
 

Role of hospitalists

Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.

Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.¹³ However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.

We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf

2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219

3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/

4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.

5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.

6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.

7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.

8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.

9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.

10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.

11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22

12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).

13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later

As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).

While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.

However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
 

1. Participation in the vaccine trials by minority populations

With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.¹ Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.

Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.² Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.³

The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.

In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.

Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.

While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
 

2. Equitable allocation and distribution of vaccine for minority populations

Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.

The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
 

3. Immunization uptake by minority populations

Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.

According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.³ This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.^4-9

On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.¹⁰ Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.

When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.¹¹ It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.¹² Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
 

Role of hospitalists

Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.

Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.¹³ However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.

We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf

2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219

3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/

4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.

5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.

6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.

7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.

8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.

9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.

10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.

11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22

12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).

13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later

As COVID-19 cases soared to new daily highs across the United States, November 2020 brought some exciting and promising vaccine efficacy results. Currently, the United States has four COVID-19 vaccines in phase 3 trials: the Moderna vaccine (mRNA-1273), the Oxford/AstraZeneca vaccine (AZD1222), Pfizer/BioNTech’s (BNT162), and the Johnson & Johnson vaccine (JNJ-78436735).

While Pfizer/ BioNTech and Moderna received fast-track designation by the Food and Drug Administration, AZD1222 and JNJ-78436735 trials were resumed after a temporary hold. Pfizer/BioNTech and Moderna have also submitted an emergency-use authorization application to the FDA after favorable results from a completed phase 3 clinical trial. The results so far seem promising, with Oxford/AstraZeneca’s combined analysis from different dosing regimens resulting in an average efficacy of 70%. Pfizer/ BioNTech and Moderna have each reported vaccines that are 90% and 95% effective respectively in trials.

However, even with a safe and effective vaccine, there must be an equal emphasis on a successful coronavirus vaccine program’s three pillars in the communities that are the hardest hit: participation in the vaccine trials by minority populations, equitable allocation and distribution of vaccine for minority populations, and immunization uptake by minority populations.
 

1. Participation in the vaccine trials by minority populations

With a great emphasis on the inclusion of diverse populations, the Moderna vaccine clinical trials gained participation by racial and ethnic minorities. As of Oct. 21, 2020, the Moderna vaccine trial participants were 10% African American, 20% Hispanic, 4% Asian, 63% White, and 3% other.¹ Pharmaceutical giant Pfizer also had approximately 42% of overall – and 45% of U.S. – participants from diverse backgrounds. The proportional registration of racially and ethnically diverse participants in other vaccine trials is also anticipated to be challenging.

Though there has been an improvement in minority participation in COVID-19 vaccine trials, it is still below the ideal representation when compared with U.S. census data.² Ideally, participants in a clinical trial should represent the U.S. population to get a full picture of a medical product’s risks and benefits. However, recruitment rates in clinical trials have remained low among minorities for various reasons. Historically, African Americans make up only 5% of participants in U.S. clinical trials, while they represent 13% of the country’s general population; likewise, Hispanics are also underrepresented.³

The legacy of distrust in the medical system is deep-rooted and is one of the most substantial barriers to clinical trial participation. A plethora of unethical trials and experiments on the African American population have left a lasting impact. The most infamous and widely known was the “Tuskegee Study,” conducted by the United States Public Health Service to “observe the natural history of untreated syphilis” in Black populations. In the study, performed without informed consent, Black men with latent or late syphilis received no treatment, even after penicillin was discovered as a safe and reliable cure for syphilis. This human experimentation lasted for 40 years, resulting in 128 male patients who died from syphilis or its complications, 40 of their spouses infected, and 19 of their children with acquired congenital syphilis.

In another case, the father of modern gynecology, J. Marion Sims, allegedly performed experimental surgeries on enslaved Black women without consent. For more than 4 decades, North Carolina’s statewide eugenics program forcibly sterilized almost 7,600 people, many of whom were Black. Another story of exploitation involves Henrietta Lacks, whose cancer cells are the source of the HeLa cell line, responsible for some of the most important medical advances of all time. Though her cells were commercialized and generated millions for medical researchers, neither Ms. Lacks nor her family knew the cell cultures existed until more than 20 years after her death from cervical cancer. Many years later, victims and families of the Tuskegee experiment, individuals sterilized by the Eugenics Board of North Carolina, and the family of Henrietta Lacks received compensation, and Sims’s statue was taken down in 2018. Not too long ago, many criticized the FDA’s “Exception from Informed Consent policy” for compromising patients’ exercise of autonomy, and concern for overrepresenting African Americans in the U.S. EFIC trials.

Racial disparities in medical treatment and unconscious biases among providers are among the reasons for mistrust and lack of trial participation by minority populations today. Francis Collins, director of the National Institutes of Health, said that recent social upheaval sparked by the death of George Floyd has likely added to feelings of mistrust between minority groups and government or pharmaceutical companies. “Yet we need their participation if this is going to have a meaningful outcome,” he said.

While “Operation Warp Speed” is committed to developing and delivering a COVID-19 vaccine rapidly while adhering to safety and efficacy standards, the challenges to enrolling people from racial and ethnic minorities in trials have been a concern. The political partisanship and ever-shifting stances on widespread COVID-19 testing, use of facemasks, endorsement of unproven drugs for the disease, and accusations against the FDA for delaying human trials for the vaccine have contributed to the skepticism as well. Tremendous pressure for a rushed vaccine with unrealistic timelines, recent holds on AZD1222 and JNJ-78436735 as well as the AZD1222 dosage error during trials have also raised skepticism of the safety and efficacy of vaccine trials.
 

2. Equitable allocation and distribution of vaccine for minority populations

Enrollment in clinical trials is just a beginning; a more significant challenge would be the vaccine’s uptake when available to the general public. We still lack a consensus on whether it is lawful for race to be an explicit criterion for priority distribution of the COVID-19 vaccine. Recently the Centers for Disease Control and Prevention suggested that the vaccine amount allotted to jurisdictions might be based on critical populations recommended for vaccination by the Advisory Committee on Immunization Practices with input from the National Academies of Sciences, Engineering, and Medicine.

The NASEM framework lays out four-phased vaccine distribution approaches, emphasizing social equity by prioritizing vaccines for geographic areas identified through CDC’s social vulnerability index (SVI) or another more specific index. SVI has been a robust composite marker of minority status and language, household composition and transportation, and housing and disability, and predicted COVID-19 case counts in the United States in several studies. The National Academy of Medicine has also recommended racial minorities receive priority vaccination because they have been hard hit and are “worse off” socioeconomically.
 

3. Immunization uptake by minority populations

Though minority participation is crucial in developing the vaccine, more transparency, open discussions on ethical distribution, and awareness of side effects are required before vaccine approval or emergency-use authorization. Companies behind the four major COVID-19 vaccines in development have released their trials’ protocols, details on vaccine efficacy, and each product’s makeup to increase acceptance of the vaccine.

According to a recent Pew research study, about half of U.S. adults (51%) now say they would definitely or probably get a vaccine to prevent COVID-19 if it were available today. Nearly as many (49%) say they definitely or probably would not get vaccinated at this time. Intent to get a COVID-19 vaccine has fallen from 72% in May 2020, a 21–percentage point drop, and Black adults were much less likely to say they would get a vaccine than other Americans.³ This is concerning as previous studies have shown that race and ethnicity can influence immune responses to vaccination. There is evidence of racial and ethnic differences in immune response following rubella vaccination, Hib–tetanus toxoid conjugate vaccine, antibody responses to the influenza A virus components of IIV3 or 4, and immune responses after measles vaccination.^4-9

On the other hand, significant differences in reporting rates of adverse events after human papillomavirus vaccinations were found in different race and ethnicity groups in the Vaccine Adverse Event Reporting System.¹⁰ Thus, there is ample evidence that race and ethnicity affect responsiveness to a vaccine. Inequity in participation in a clinical trial may lead to an ineffective or one with a suboptimal response or even an unsafe vaccine.

When we look at other immunization programs, according to various surveys in recent years, non-Hispanic Blacks have lower annual vaccination rates for flu, pneumonia, and human papillomavirus vaccinations nationally, compared with non-Hispanic White adults.¹¹ It is a cause of concern as a proportion of the population must be vaccinated to reach “community immunity” or “herd immunity” from vaccination. Depending on varying biological, environmental, and sociobehavioral factors, the threshold for COVID-19 herd immunity may be between 55% and 82% of the population.¹² Hence, neither a vaccine trial nor an immunization program can succeed without participation from all communities and age groups.
 

Role of hospitalists

Hospitalists, who give immunizations as part of the hospital inpatient quality reporting program, are uniquely placed in this pandemic. Working on the front lines, we may encounter questions, concerns, rejections, and discussions about the pros and cons of the COVID-19 vaccine from patients.

Investigators at Children’s National Hospital and George Washington University, both in Washington, recently recommended three steps physicians and others can take now to ensure more people get the COVID-19 vaccine when it is available. Engaging frontline health professionals was one of the suggested steps to encourage more people to get the vaccine.¹³ However, it is imperative to understand that vaccine hesitancy might be an issue for health care providers as well, if concerns for scientific standards and involvement of diverse populations are not addressed.

We are only starting to develop a safe and effective immunization program. We must bring more to unrepresented communities than just vaccine trials. Information, education, availability, and access to the vaccines will make for a successful COVID-19 immunization program.

Dr. Saigal is a hospitalist and clinical assistant professor of medicine in the division of hospital medicine at the Ohio State University Wexner Medical Center, Columbus.

References

1. Moderna. COVE study. 2020 Oct 21. https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf

2. U.S. Census Bureau. Quick facts: Population estimates, July 1, 2019. https://www.census.gov/quickfacts/fact/table/US/PST045219

3. Pew Research Center. U.S. Public Now Divided Over Whether To Get COVID-19 Vaccine. 2020 Sep 17. https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/

4. Haralambieva IH et al. Associations between race sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946-53.

5. McQuillan GM et al. Seroprevalence of measles antibody in the U.S. population 1999-2004. J Infect Dis. 2007;196:1459–64. doi: 10.1086/522866.

6. Christy C et al. Effect of gender race and parental education on immunogenicity and reported reactogenicity of acellular and whole-cell pertussis vaccines. Pediatrics. 1995;96:584-7.

7. Poland GA et al. Measles antibody seroprevalence rates among immunized Inuit Innu and Caucasian subjects. Vaccine. 1999;17:1525-31.

8. Greenberg DP et al. Immunogenicity of Haemophilus influenzae type b tetanus toxoid conjugate vaccine in young infants. The Kaiser-UCLA Vaccine Study Group. J Infect Dis. 1994;170:76-81.

9. Kurupati R et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct prevaccination gene expression profiles in blood. Oncotarget. 2016;7(39):62898-911.

10. Huang J et al. Characterization of the differential adverse event rates by race/ethnicity groups for HPV vaccine by integrating data from different sources. Front Pharmacol. 2018;9:539.

11. https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=4&lvlid=22

12. Sanche S et al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7).

13. American Medical Association. How to ready patients now so they’ll get a COVID-19 vaccine later. 2020 May 27. https://www.ama-assn.org/delivering-care/public-health/how-ready-patients-now-so-they-ll-get-covid-19-vaccine-later

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

The news on children and COVID-19 for Thanksgiving week does not provide a lot of room for thankfulness.

“The number of new child COVID-19 cases reported this week, nearly 154,000, is the highest weekly increase since the pandemic began,” the American Academy of Pediatrics and the Children’s Hospital Association said in their latest weekly report.

For those not counting, the week ending Nov. 26 was the fifth in a row to show “the highest weekly increase since the pandemic began,” based on data the AAP and CHA have been collecting from 49 state health departments (New York does not report ages), as well as the District of Columbia, New York City, Puerto Rico, and Guam.

The 153,608 new cases bring the total number of COVID-19 cases in children to almost 1.34 million in those jurisdictions, which is 12% of the total number of cases (11.2 million) among all ages. For just the week ending Nov. 26, children represented 13.7% of all new cases in the United States, down from 14.1% the previous week, according to the AAP/CHA data.

Among the states reporting child cases, Florida has the lowest cumulative proportion of child cases, 6.4%, but the state is using an age range of 0-14 years (no other state goes lower than 17 years). New Jersey and Texas are next at 6.9%, although Texas “reported age for only 6% of total confirmed cases,” the AAP and CHA noted.

There are 35 states above the national number of 12.0%, the highest being Wyoming at 23.3%, followed by Tennessee at 18.3% and South Carolina at 18.2%. The two southern states are the only ones to use an age range of 0-20 years for child cases, the two groups said in this week’s report, which did not include the usual data on testing, hospitalization, and mortality because of the holiday.

[email protected]

Alcohol withdrawal syndrome (AWS) occurs when an individual who is alcohol-dependent suddenly stops or significantly reduces his/her alcohol intake.¹ Symptoms of AWS, which can be fatal, include anxiety, restlessness, seizures, confusion, and delirium.¹ Because benzodiazepines have been proven effective in improving symptoms of AWS, they are considered the first-line treatment, but they also carry the risk of abuse, psychomotor sedation, cognitive impairment, and interactions with alcohol.¹

Non-benzodiazepine anticonvulsants (NBACs) such as valproic acid (VPA) and carbamazepine may offer benefit as alternatives or adjuncts to benzodiazepines.¹ Many NBACs affect the functioning of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters,² which are particularly dysregulated in patients with AWS. Because NBACs help stabilize this imbalance, they may be useful for managing AWS and preventing relapse without the risks associated with benzodiazepines.²

Valproic acid: A better choice than carbamazepine

Compared with other NBACs, VPA and carbamazepine have been studied more extensively for treating patients with AWS, and their clinical effectiveness has been well documented.¹ For mild-to-moderate AWS, VPA and carbamazepine may be as effective as benzodiazepines in reducing the severity of symptoms, and more potent for preventing withdrawal seizures.¹

Increasing data suggests that compared with VPA, adjunctive treatment with carbamazepine for AWS may be more frequently associated with intolerable adverse effects such as ataxia, orthostatic hypotension, vertigo, nausea, and vomiting.¹ The rapid onset of AWS requires rapid-acting pharmacotherapy.¹ In attempting to rapidly achieve the desired plasma concentrations of carbamazepine, clinicians may risk inducing adverse effects. Compared with carbamazepine, VPA is associated with faster symptom resolution, a shorter duration of pharmacologic treatment, fewer transfers to the ICU, fewer withdrawal seizures, and a more favorable adverse effect profile.¹ Likely due to its shorter half-life, VPA delivers its therapeutic effects without producing significant adverse effects.¹

Early and aggressive treatment of AWS is needed to block kindling,³ which is characterized by the worsening of withdrawal symptoms each time an individual attempts to quit drinking alcohol. Compared with carbamazepine, VPA may be more helpful for blocking kindling.³

More data is needed

Due to ethical concerns, few studies have compared anticonvulsant medications with placebo for treating AWS.² Most studies examining NBACs for AWS have either used the anticonvulsant as an adjunct to a benzodiazepine to examine improvement in withdrawal symptoms, or compared the anticonvulsant with placebo or another intervention to assess the amount of a benzodiazepine required for safe detoxification.^2,4 Additionally, most studies examining NBACs have been short, and few followed patients after the active medication period, which limits our knowledge of the long-term effectiveness of NBACs.² Before NBACs can replace benzodiazepines for managing AWS, further evidence from clinical trials is needed to assess their efficiency as a stand-alone treatment.

Alcohol withdrawal syndrome (AWS) occurs when an individual who is alcohol-dependent suddenly stops or significantly reduces his/her alcohol intake.¹ Symptoms of AWS, which can be fatal, include anxiety, restlessness, seizures, confusion, and delirium.¹ Because benzodiazepines have been proven effective in improving symptoms of AWS, they are considered the first-line treatment, but they also carry the risk of abuse, psychomotor sedation, cognitive impairment, and interactions with alcohol.¹

Non-benzodiazepine anticonvulsants (NBACs) such as valproic acid (VPA) and carbamazepine may offer benefit as alternatives or adjuncts to benzodiazepines.¹ Many NBACs affect the functioning of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters,² which are particularly dysregulated in patients with AWS. Because NBACs help stabilize this imbalance, they may be useful for managing AWS and preventing relapse without the risks associated with benzodiazepines.²

Valproic acid: A better choice than carbamazepine

Compared with other NBACs, VPA and carbamazepine have been studied more extensively for treating patients with AWS, and their clinical effectiveness has been well documented.¹ For mild-to-moderate AWS, VPA and carbamazepine may be as effective as benzodiazepines in reducing the severity of symptoms, and more potent for preventing withdrawal seizures.¹

Increasing data suggests that compared with VPA, adjunctive treatment with carbamazepine for AWS may be more frequently associated with intolerable adverse effects such as ataxia, orthostatic hypotension, vertigo, nausea, and vomiting.¹ The rapid onset of AWS requires rapid-acting pharmacotherapy.¹ In attempting to rapidly achieve the desired plasma concentrations of carbamazepine, clinicians may risk inducing adverse effects. Compared with carbamazepine, VPA is associated with faster symptom resolution, a shorter duration of pharmacologic treatment, fewer transfers to the ICU, fewer withdrawal seizures, and a more favorable adverse effect profile.¹ Likely due to its shorter half-life, VPA delivers its therapeutic effects without producing significant adverse effects.¹

Early and aggressive treatment of AWS is needed to block kindling,³ which is characterized by the worsening of withdrawal symptoms each time an individual attempts to quit drinking alcohol. Compared with carbamazepine, VPA may be more helpful for blocking kindling.³

More data is needed

Due to ethical concerns, few studies have compared anticonvulsant medications with placebo for treating AWS.² Most studies examining NBACs for AWS have either used the anticonvulsant as an adjunct to a benzodiazepine to examine improvement in withdrawal symptoms, or compared the anticonvulsant with placebo or another intervention to assess the amount of a benzodiazepine required for safe detoxification.^2,4 Additionally, most studies examining NBACs have been short, and few followed patients after the active medication period, which limits our knowledge of the long-term effectiveness of NBACs.² Before NBACs can replace benzodiazepines for managing AWS, further evidence from clinical trials is needed to assess their efficiency as a stand-alone treatment.

Alcohol withdrawal syndrome (AWS) occurs when an individual who is alcohol-dependent suddenly stops or significantly reduces his/her alcohol intake.¹ Symptoms of AWS, which can be fatal, include anxiety, restlessness, seizures, confusion, and delirium.¹ Because benzodiazepines have been proven effective in improving symptoms of AWS, they are considered the first-line treatment, but they also carry the risk of abuse, psychomotor sedation, cognitive impairment, and interactions with alcohol.¹

Non-benzodiazepine anticonvulsants (NBACs) such as valproic acid (VPA) and carbamazepine may offer benefit as alternatives or adjuncts to benzodiazepines.¹ Many NBACs affect the functioning of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters,² which are particularly dysregulated in patients with AWS. Because NBACs help stabilize this imbalance, they may be useful for managing AWS and preventing relapse without the risks associated with benzodiazepines.²

Valproic acid: A better choice than carbamazepine

Compared with other NBACs, VPA and carbamazepine have been studied more extensively for treating patients with AWS, and their clinical effectiveness has been well documented.¹ For mild-to-moderate AWS, VPA and carbamazepine may be as effective as benzodiazepines in reducing the severity of symptoms, and more potent for preventing withdrawal seizures.¹

Increasing data suggests that compared with VPA, adjunctive treatment with carbamazepine for AWS may be more frequently associated with intolerable adverse effects such as ataxia, orthostatic hypotension, vertigo, nausea, and vomiting.¹ The rapid onset of AWS requires rapid-acting pharmacotherapy.¹ In attempting to rapidly achieve the desired plasma concentrations of carbamazepine, clinicians may risk inducing adverse effects. Compared with carbamazepine, VPA is associated with faster symptom resolution, a shorter duration of pharmacologic treatment, fewer transfers to the ICU, fewer withdrawal seizures, and a more favorable adverse effect profile.¹ Likely due to its shorter half-life, VPA delivers its therapeutic effects without producing significant adverse effects.¹

Early and aggressive treatment of AWS is needed to block kindling,³ which is characterized by the worsening of withdrawal symptoms each time an individual attempts to quit drinking alcohol. Compared with carbamazepine, VPA may be more helpful for blocking kindling.³

More data is needed

Due to ethical concerns, few studies have compared anticonvulsant medications with placebo for treating AWS.² Most studies examining NBACs for AWS have either used the anticonvulsant as an adjunct to a benzodiazepine to examine improvement in withdrawal symptoms, or compared the anticonvulsant with placebo or another intervention to assess the amount of a benzodiazepine required for safe detoxification.^2,4 Additionally, most studies examining NBACs have been short, and few followed patients after the active medication period, which limits our knowledge of the long-term effectiveness of NBACs.² Before NBACs can replace benzodiazepines for managing AWS, further evidence from clinical trials is needed to assess their efficiency as a stand-alone treatment.

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

A federal advisory panel recommends that health care workers and residents of long-term care facilities be the first to receive a COVID-19 vaccine when one is authorized for use by the Food and Drug Administration.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.

The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.

“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.

Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.

“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.

“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”

CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.

But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.

She added: “I have no reservations for health care workers taking this vaccine.”
 

Prioritization could change

The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.

“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.

He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.

A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.

“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.

ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
 

Staggered immunization subprioritization urged

The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.

“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.

The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.

Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.

Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.

The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.

ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.

This article first appeared on Medscape.com.

Editor’s note: Psychiatry Leaders’ Perspectives is a new department in Current Psychiatry in which we interview a prominent psychiatrist about the strengths, weaknesses, opportunities, and threats facing the field of psychiatry.

In this first Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Dilip V. Jeste, MD. Dr. Jeste is Senior Associate Dean for Healthy Aging and Senior Care, Estelle and Edgar Levi Memorial Chair in Aging, Director of the Sam and Rose Stein Institute for Research on Aging, Distinguished Professor of Psychiatry and Neurosciences, University of California San Diego; and Co-Director of the UC San Diego-IBM Center on Artificial Intelligence for Healthy Living. His main areas of research include schizophrenia, neuro­psychiatric interventions, and successful aging. He served as the 139th President of the American Psychiatric Association (APA) and also is a past president of the American Association for Geriatric Psychiatry, the West Coast College of Biological Psychiatry, and founding president of International College of Geriatric Psychoneuropharmacology.

Dr. Aftab: The focus of your term as president of the APA was on “positive psychiatry.” You are also one of the world’s foremost experts in this area. How successful have you been in your mission to promote positive psychiatry, and how has your message been received?

Dr. Jeste: Let me start with a little bit of background about why I got into positive psychiatry. As a geriatric psychiatrist, my research work has brought me face to face with the paradox of aging: although physical health declines with age, mental health and well-being improve on average. This is the case not just for individuals in the community but also for individuals with serious mental illnesses. That got me into thinking more and more about the ways in which we can bring positive change in the lives of patients. When I became the president of the APA, one of my main tasks was to finalize and publish the DSM-5, which rightly focuses on the disorders we treat, but it also provided me with an opportunity to highlight the side of psychiatry that focuses on the positive aspects of our own and our patients’ lives, such as wisdom, resilience, meaning, and social connectedness.

As is the case with any new idea, there is a lot of resistance in the beginning and this will always be the case. However, I would say that positive psychiatry has been received very well. We now have an APA Caucus and a World Psychiatric Association Section on positive psychiatry. Our book, Positive Psychiatry, turned out to be one of the best sellers for American Psychiatric Publishing! Every year, there are symposia on positive psychiatry and papers and books from other countries. Overall, the reception has been very promising.

Dr. Aftab: Thank you for this interesting background, Dr. Jeste. Now let me ask you about the current state of psychiatry. What do you see as some of the strengths of our profession?

Dr. Jeste: Psychiatry’s unique strength is our skill in promoting adaptive behavior change, with a focus on positive factors such as resilience, wisdom, optimism, social engagement, improved health, and longevity. If you look at the research literature, the effect sizes of factors such as optimism, resilience, and social engagement are equal to or greater than interventions such as statins, smoking cessation, and exercise. Cardiothoracic surgeons and radiologists can’t help people increase their resilience, optimism, and social engagement, but psychiatrists can. Behavior change is our expertise. When people are suicidal, we give them hope; we help depressed individuals become active, productive, and happy. We treat people with schizophrenia and bipolar disorder, reduce their psychopathological behaviors, and improve their everyday functioning.

Continue to: Dr. Aftab

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Jeste: Unfortunately, there are a lot of restrictions posed by the current reimbursement system. As a result, psychiatrists spend most of their time prescribing medications in clinical practice. I have nothing against psychopharmacology, but we also need to focus on important aspects of our lives, such as lifestyle, cognitive attitudes, self-care, and social engagement. We need to go beyond symptom reduction. A prominent example is loneliness, which is a major risk factor for morbidity and mortality; the treatment for loneliness is not increasing social network, it’s actually changing one’s perception of and ability to enhance appropriate socialization. Who can do that? Psychiatrists! But we don’t do that right now because the health insurance system doesn’t reimburse psychiatrists to do that.

Dr. Aftab: What is your perception of the threats that psychiatry faces? You had to fend off a variety of challenges during your year as APA president, such as issues surrounding revision of DSM-5. How has that experience shaped your assessment?

Dr. Jeste: I was honored to oversee the finalization and publication of DSM-5 as the president of the APA, even though I lost a lot of sleep working on it! What I found was that there was a lot of antagonism in the media, as well as among several advocacy groups, about the DSM. The misperception was that psychiatry and the APA were trying to expand diagnoses so that the drug companies could sell medications to more people, and psychiatry would benefit from this because of its relationship with the industry. That was actually not the case at all. What I tried to do was to understand where these groups were coming from, and to treat them as collaborators and partners, not as enemies. One thing I am particularly proud of is that we established the Summit Group for DSM-5, which brought together perspectives of the various stakeholders, and our communication both within and outside of the APA improved significantly. It’s gratifying to note that much of the controversy in the media died down after DSM-5 was published. The often-critical New York Times wrote that while DSM-5 is far from perfect, it is the best we have today clinically, and I’m very proud of the work we did on it.

Dr. Aftab: What sort of opportunities lie ahead for psychiatry? What do you envision for the future of the field?

Continue to: Dr. Jeste

Dr. Jeste: As a neuroscientist, I’m excited about the new developments in brain science. Our understanding of the neurobiologic basis of mental illnesses is slowly but surely increasing. I’m also very heartened by all the research going on with regard to the prevention of mental illnesses. I think we will be able to reduce the risk of many psychiatric disorders in the future. This is an exciting time for the field, and psychiatry is going to look very different 20 years from now!

Dr. Aftab: Some people think there’s a conflict between a neuroscientific and psychosocial understanding of psychiatry. How do you think the 2 relate to each other?

Dr. Jeste: The reality, I think, is that there is no conflict. Ultimately, the mind is a function of the brain, and the mind operates within a society. Neuroscientists are also realizing the importance of psychosocial aspects, and there is a growing social neuroscience, looking at the neurobiology of things such as loneliness, social isolation, and wisdom. The effects of psychosocial interventions such as meditation and long-term cognitive-behavioral therapy on the brain are now indisputable. I like to say that psychosocial interventions are often more biological in their effects than the drugs!

Dr. Aftab: Any words of wisdom for psychiatry trainees and early career psychiatrists?

Dr. Jeste: First of all, I congratulate them for going into psychiatry, which is rapidly advancing and is the field of the future. Looking at new developments, such as in artificial intelligence, I wish I could be a young person again just getting into psychiatry! The role of psychiatrists is also evolving, and psychiatrists will become leaders of multidisciplinary teams. I would advise trainees and early career psychiatrists not to get frustrated by issues such as insurance reimbursements; these obstacles will pass. Society is becoming far more conscious of the importance of mental health to our well-being. So I see a reason to be optimistic. I would also mention that the younger generation has a lot to teach the older generation while at the same time benefitting from the wisdom they have to offer. One of the best things we can promote is intergenerational activity, both within and outside of our profession.

Editor’s note: Psychiatry Leaders’ Perspectives is a new department in Current Psychiatry in which we interview a prominent psychiatrist about the strengths, weaknesses, opportunities, and threats facing the field of psychiatry.

In this first Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Dilip V. Jeste, MD. Dr. Jeste is Senior Associate Dean for Healthy Aging and Senior Care, Estelle and Edgar Levi Memorial Chair in Aging, Director of the Sam and Rose Stein Institute for Research on Aging, Distinguished Professor of Psychiatry and Neurosciences, University of California San Diego; and Co-Director of the UC San Diego-IBM Center on Artificial Intelligence for Healthy Living. His main areas of research include schizophrenia, neuro­psychiatric interventions, and successful aging. He served as the 139th President of the American Psychiatric Association (APA) and also is a past president of the American Association for Geriatric Psychiatry, the West Coast College of Biological Psychiatry, and founding president of International College of Geriatric Psychoneuropharmacology.

Dr. Aftab: The focus of your term as president of the APA was on “positive psychiatry.” You are also one of the world’s foremost experts in this area. How successful have you been in your mission to promote positive psychiatry, and how has your message been received?

Dr. Jeste: Let me start with a little bit of background about why I got into positive psychiatry. As a geriatric psychiatrist, my research work has brought me face to face with the paradox of aging: although physical health declines with age, mental health and well-being improve on average. This is the case not just for individuals in the community but also for individuals with serious mental illnesses. That got me into thinking more and more about the ways in which we can bring positive change in the lives of patients. When I became the president of the APA, one of my main tasks was to finalize and publish the DSM-5, which rightly focuses on the disorders we treat, but it also provided me with an opportunity to highlight the side of psychiatry that focuses on the positive aspects of our own and our patients’ lives, such as wisdom, resilience, meaning, and social connectedness.

As is the case with any new idea, there is a lot of resistance in the beginning and this will always be the case. However, I would say that positive psychiatry has been received very well. We now have an APA Caucus and a World Psychiatric Association Section on positive psychiatry. Our book, Positive Psychiatry, turned out to be one of the best sellers for American Psychiatric Publishing! Every year, there are symposia on positive psychiatry and papers and books from other countries. Overall, the reception has been very promising.

Dr. Aftab: Thank you for this interesting background, Dr. Jeste. Now let me ask you about the current state of psychiatry. What do you see as some of the strengths of our profession?

Dr. Jeste: Psychiatry’s unique strength is our skill in promoting adaptive behavior change, with a focus on positive factors such as resilience, wisdom, optimism, social engagement, improved health, and longevity. If you look at the research literature, the effect sizes of factors such as optimism, resilience, and social engagement are equal to or greater than interventions such as statins, smoking cessation, and exercise. Cardiothoracic surgeons and radiologists can’t help people increase their resilience, optimism, and social engagement, but psychiatrists can. Behavior change is our expertise. When people are suicidal, we give them hope; we help depressed individuals become active, productive, and happy. We treat people with schizophrenia and bipolar disorder, reduce their psychopathological behaviors, and improve their everyday functioning.

Continue to: Dr. Aftab

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Jeste: Unfortunately, there are a lot of restrictions posed by the current reimbursement system. As a result, psychiatrists spend most of their time prescribing medications in clinical practice. I have nothing against psychopharmacology, but we also need to focus on important aspects of our lives, such as lifestyle, cognitive attitudes, self-care, and social engagement. We need to go beyond symptom reduction. A prominent example is loneliness, which is a major risk factor for morbidity and mortality; the treatment for loneliness is not increasing social network, it’s actually changing one’s perception of and ability to enhance appropriate socialization. Who can do that? Psychiatrists! But we don’t do that right now because the health insurance system doesn’t reimburse psychiatrists to do that.

Dr. Aftab: What is your perception of the threats that psychiatry faces? You had to fend off a variety of challenges during your year as APA president, such as issues surrounding revision of DSM-5. How has that experience shaped your assessment?

Dr. Jeste: I was honored to oversee the finalization and publication of DSM-5 as the president of the APA, even though I lost a lot of sleep working on it! What I found was that there was a lot of antagonism in the media, as well as among several advocacy groups, about the DSM. The misperception was that psychiatry and the APA were trying to expand diagnoses so that the drug companies could sell medications to more people, and psychiatry would benefit from this because of its relationship with the industry. That was actually not the case at all. What I tried to do was to understand where these groups were coming from, and to treat them as collaborators and partners, not as enemies. One thing I am particularly proud of is that we established the Summit Group for DSM-5, which brought together perspectives of the various stakeholders, and our communication both within and outside of the APA improved significantly. It’s gratifying to note that much of the controversy in the media died down after DSM-5 was published. The often-critical New York Times wrote that while DSM-5 is far from perfect, it is the best we have today clinically, and I’m very proud of the work we did on it.

Dr. Aftab: What sort of opportunities lie ahead for psychiatry? What do you envision for the future of the field?

Continue to: Dr. Jeste

Dr. Jeste: As a neuroscientist, I’m excited about the new developments in brain science. Our understanding of the neurobiologic basis of mental illnesses is slowly but surely increasing. I’m also very heartened by all the research going on with regard to the prevention of mental illnesses. I think we will be able to reduce the risk of many psychiatric disorders in the future. This is an exciting time for the field, and psychiatry is going to look very different 20 years from now!

Dr. Aftab: Some people think there’s a conflict between a neuroscientific and psychosocial understanding of psychiatry. How do you think the 2 relate to each other?

Dr. Jeste: The reality, I think, is that there is no conflict. Ultimately, the mind is a function of the brain, and the mind operates within a society. Neuroscientists are also realizing the importance of psychosocial aspects, and there is a growing social neuroscience, looking at the neurobiology of things such as loneliness, social isolation, and wisdom. The effects of psychosocial interventions such as meditation and long-term cognitive-behavioral therapy on the brain are now indisputable. I like to say that psychosocial interventions are often more biological in their effects than the drugs!

Dr. Aftab: Any words of wisdom for psychiatry trainees and early career psychiatrists?

Dr. Jeste: First of all, I congratulate them for going into psychiatry, which is rapidly advancing and is the field of the future. Looking at new developments, such as in artificial intelligence, I wish I could be a young person again just getting into psychiatry! The role of psychiatrists is also evolving, and psychiatrists will become leaders of multidisciplinary teams. I would advise trainees and early career psychiatrists not to get frustrated by issues such as insurance reimbursements; these obstacles will pass. Society is becoming far more conscious of the importance of mental health to our well-being. So I see a reason to be optimistic. I would also mention that the younger generation has a lot to teach the older generation while at the same time benefitting from the wisdom they have to offer. One of the best things we can promote is intergenerational activity, both within and outside of our profession.

Editor’s note: Psychiatry Leaders’ Perspectives is a new department in Current Psychiatry in which we interview a prominent psychiatrist about the strengths, weaknesses, opportunities, and threats facing the field of psychiatry.

In this first Psychiatry Leaders’ Perspectives, Awais Aftab, MD, interviewed Dilip V. Jeste, MD. Dr. Jeste is Senior Associate Dean for Healthy Aging and Senior Care, Estelle and Edgar Levi Memorial Chair in Aging, Director of the Sam and Rose Stein Institute for Research on Aging, Distinguished Professor of Psychiatry and Neurosciences, University of California San Diego; and Co-Director of the UC San Diego-IBM Center on Artificial Intelligence for Healthy Living. His main areas of research include schizophrenia, neuro­psychiatric interventions, and successful aging. He served as the 139th President of the American Psychiatric Association (APA) and also is a past president of the American Association for Geriatric Psychiatry, the West Coast College of Biological Psychiatry, and founding president of International College of Geriatric Psychoneuropharmacology.

Dr. Aftab: The focus of your term as president of the APA was on “positive psychiatry.” You are also one of the world’s foremost experts in this area. How successful have you been in your mission to promote positive psychiatry, and how has your message been received?

Dr. Jeste: Let me start with a little bit of background about why I got into positive psychiatry. As a geriatric psychiatrist, my research work has brought me face to face with the paradox of aging: although physical health declines with age, mental health and well-being improve on average. This is the case not just for individuals in the community but also for individuals with serious mental illnesses. That got me into thinking more and more about the ways in which we can bring positive change in the lives of patients. When I became the president of the APA, one of my main tasks was to finalize and publish the DSM-5, which rightly focuses on the disorders we treat, but it also provided me with an opportunity to highlight the side of psychiatry that focuses on the positive aspects of our own and our patients’ lives, such as wisdom, resilience, meaning, and social connectedness.

As is the case with any new idea, there is a lot of resistance in the beginning and this will always be the case. However, I would say that positive psychiatry has been received very well. We now have an APA Caucus and a World Psychiatric Association Section on positive psychiatry. Our book, Positive Psychiatry, turned out to be one of the best sellers for American Psychiatric Publishing! Every year, there are symposia on positive psychiatry and papers and books from other countries. Overall, the reception has been very promising.

Dr. Aftab: Thank you for this interesting background, Dr. Jeste. Now let me ask you about the current state of psychiatry. What do you see as some of the strengths of our profession?

Dr. Jeste: Psychiatry’s unique strength is our skill in promoting adaptive behavior change, with a focus on positive factors such as resilience, wisdom, optimism, social engagement, improved health, and longevity. If you look at the research literature, the effect sizes of factors such as optimism, resilience, and social engagement are equal to or greater than interventions such as statins, smoking cessation, and exercise. Cardiothoracic surgeons and radiologists can’t help people increase their resilience, optimism, and social engagement, but psychiatrists can. Behavior change is our expertise. When people are suicidal, we give them hope; we help depressed individuals become active, productive, and happy. We treat people with schizophrenia and bipolar disorder, reduce their psychopathological behaviors, and improve their everyday functioning.

Continue to: Dr. Aftab

Dr. Aftab: Are there ways in which the status quo in psychiatry falls short of the ideal? What are our areas of relative weakness?

Dr. Jeste: Unfortunately, there are a lot of restrictions posed by the current reimbursement system. As a result, psychiatrists spend most of their time prescribing medications in clinical practice. I have nothing against psychopharmacology, but we also need to focus on important aspects of our lives, such as lifestyle, cognitive attitudes, self-care, and social engagement. We need to go beyond symptom reduction. A prominent example is loneliness, which is a major risk factor for morbidity and mortality; the treatment for loneliness is not increasing social network, it’s actually changing one’s perception of and ability to enhance appropriate socialization. Who can do that? Psychiatrists! But we don’t do that right now because the health insurance system doesn’t reimburse psychiatrists to do that.

Dr. Aftab: What is your perception of the threats that psychiatry faces? You had to fend off a variety of challenges during your year as APA president, such as issues surrounding revision of DSM-5. How has that experience shaped your assessment?

Dr. Jeste: I was honored to oversee the finalization and publication of DSM-5 as the president of the APA, even though I lost a lot of sleep working on it! What I found was that there was a lot of antagonism in the media, as well as among several advocacy groups, about the DSM. The misperception was that psychiatry and the APA were trying to expand diagnoses so that the drug companies could sell medications to more people, and psychiatry would benefit from this because of its relationship with the industry. That was actually not the case at all. What I tried to do was to understand where these groups were coming from, and to treat them as collaborators and partners, not as enemies. One thing I am particularly proud of is that we established the Summit Group for DSM-5, which brought together perspectives of the various stakeholders, and our communication both within and outside of the APA improved significantly. It’s gratifying to note that much of the controversy in the media died down after DSM-5 was published. The often-critical New York Times wrote that while DSM-5 is far from perfect, it is the best we have today clinically, and I’m very proud of the work we did on it.

Dr. Aftab: What sort of opportunities lie ahead for psychiatry? What do you envision for the future of the field?

Continue to: Dr. Jeste

Dr. Jeste: As a neuroscientist, I’m excited about the new developments in brain science. Our understanding of the neurobiologic basis of mental illnesses is slowly but surely increasing. I’m also very heartened by all the research going on with regard to the prevention of mental illnesses. I think we will be able to reduce the risk of many psychiatric disorders in the future. This is an exciting time for the field, and psychiatry is going to look very different 20 years from now!

Dr. Aftab: Some people think there’s a conflict between a neuroscientific and psychosocial understanding of psychiatry. How do you think the 2 relate to each other?

Dr. Jeste: The reality, I think, is that there is no conflict. Ultimately, the mind is a function of the brain, and the mind operates within a society. Neuroscientists are also realizing the importance of psychosocial aspects, and there is a growing social neuroscience, looking at the neurobiology of things such as loneliness, social isolation, and wisdom. The effects of psychosocial interventions such as meditation and long-term cognitive-behavioral therapy on the brain are now indisputable. I like to say that psychosocial interventions are often more biological in their effects than the drugs!

Dr. Aftab: Any words of wisdom for psychiatry trainees and early career psychiatrists?

Dr. Jeste: First of all, I congratulate them for going into psychiatry, which is rapidly advancing and is the field of the future. Looking at new developments, such as in artificial intelligence, I wish I could be a young person again just getting into psychiatry! The role of psychiatrists is also evolving, and psychiatrists will become leaders of multidisciplinary teams. I would advise trainees and early career psychiatrists not to get frustrated by issues such as insurance reimbursements; these obstacles will pass. Society is becoming far more conscious of the importance of mental health to our well-being. So I see a reason to be optimistic. I would also mention that the younger generation has a lot to teach the older generation while at the same time benefitting from the wisdom they have to offer. One of the best things we can promote is intergenerational activity, both within and outside of our profession.

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies in adults with drug-resistant epilepsy.

Just as in children with epilepsy, ketogenic diet therapies can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group said.

Novel in adult neurology

Ketogenic diet therapies are high-fat, low-carbohydrate, and adequate-protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, ketogenic diet therapies remain novel in adult neurology.

Furthermore, while there are established guidelines for ketogenic diet therapies to reduce seizures in children, there were no formal recommendations for adults, until now.

Drawing on the experience of experts at 20 centers using ketogenic diet therapies in more than 2,100 adults with epilepsy in 10 countries, Dr. Cervenka and an international team developed recommendations on use of ketogenic diet therapies in adults.

The panel noted, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, ketogenic diet therapies should be part of the repertoire of available options.”

Ketogenic diet therapies are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they said. These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome, genetic generalized epilepsies, and focal epilepsies caused by underlying migrational disorders and resistant to antiseizure medication.

However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel said.
 

A focus on compliance

Experts at nearly all of the centers report using two or more ketogenic diet therapies. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment. More than half of the centers (58%) use medium-chain triglyceride oil in combination with another ketogenic diet therapy to boost ketone body production.

The most important factors influencing the choice of ketogenic diet therapy are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).

The panel recommended that ketogenic diet therapies be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.

“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Dr. Cervenka.

The panel recommended providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction.

“In pediatric practice, positive responders typically remain on a ketogenic diet therapy for 2 years before considering weaning. Ketogenic diet therapy in adults is not time-limited. However, a minimum of 3 months of ketogenic diet therapy is recommended before any judgment of response is made,” the panel advised.

The panel pointed out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults. However, they added that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to ketogenic diet therapy use.”
 

Beyond epilepsy

The guidelines also call for pre–ketogenic diet therapy biochemical studies to screen adults for preexisting abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.

They also noted that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.

Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.

The guidelines also call for ketone monitoring (blood beta-hydroxybutyrate or urine amino acids) during the early months of ketogenic diet therapy as an objective indication of compliance and biochemical response.

Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.

Adults on a ketogenic diet therapy should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.

The panel said emerging evidence also supports the use of ketogenic diet therapies in other adult neurologic disorders such as migraine, Parkinson’s disease, dementia, and multiple sclerosis.

However, the panel said further evidence is needed to guide recommendations on use of ketogenic diet therapies in other neurologic conditions.

The research had no targeted funding. Dr. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, the Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.

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

Finally, 2020 is coming to an end, but the agony its viral pandemic inflicted on the entire world population will continue for a long time. And much as we would like to forget its damaging effects, it will surely be etched into our brains for the rest of our lives. The children who suffered the pain of the coronavirus disease 2019 (COVID-19) pandemic will endure its emotional scars for the rest of the 21st century.

Reading about the plagues of the past doesn’t come close to experiencing it and suffering through it. COVID-19 will continue to have ripple effects on every aspect of life on this planet, on individuals and on societies all over the world, especially on the biopsychosocial well-being of billions of humans around the globe.

Unprecedented disruptions

Think of the unprecedented disruptions inflicted by the trauma of the COVID-19 pandemic on our neural circuits. One of the wonders of the human brain is its continuous remodeling due to experiential neuroplasticity, and the formation of dendritic spines that immediately encode the memories of every experience. The turmoil of 2020 and its virulent pandemic will be forever etched into our collective brains, especially in our hippocampi and amygdalae. The impact on the developing brains of our children and grandchildren could be profound and may induce epigenetic changes that trigger psychopathology in the future.^1,2

As with the dinosaurs, the 2020 pandemic is like a “viral asteroid” that left devastation on our social fabric and psychological well-being in its wake. We now have deep empathy with our 1918 ancestors and their tribulations, although so far, in the United States the proportion of people infected with COVID-19 (3% as of mid-November 2020³) is dwarfed by the proportion infected with the influenza virus a century ago (30%). As of mid-November 2020, the number of global COVID-19 deaths (1.3 million³) was a tiny fraction of the 1918 influenza pandemic deaths (50 million worldwide and 675,000 in the United States⁴). Amazingly, researchers did not even know whether the killer germ was a virus or a bacterium until 1930, and it then took another 75 years to decode the genome of the influenza virus in 2005. In contrast, it took only a few short weeks to decode the genome of the virus that causes COVID-19 (severe acute respiratory syndrome-related coronavirus 2), and to begin developing multiple vaccines “at warp speed.” No vaccine or therapies were ever developed for victims of the 1918 pandemic.

An abundance of articles has been published about the pandemic since it ambushed us early in 2020, including many in Current Psychiatry.^5-21 But these publications don’t do justice to the emotional toll of living through the pandemic and witnessing its multi­farious repercussions (Table). It was truly bizarre and shocking for us to see our society and all its components literally come to a standstill, forcing the population to stop working, reducing us to simply “existing” inside our homes, with no socializing, traveling, or interacting. More unbearable than the sudden emptiness and paralysis was the unremitting fear, laced with a profound uncertainty of what was to come or when it would end.

Most psychiatrists are familiar with the Holmes and Rahe Stress Scale,²² which contains 43 life events that cumulatively can progressively increase the odds of physical illness. It is likely that most of the world’s population will score very high on the Holmes and Rahe Stress Scale, which would predict an increased risk of medical illness, even after the pandemic subsides.

Exacerbating the situation is that hospitals and clinics had to shut down most of their operations to focus their resources on treating patients with COVID-19 in ICUs. This halted all routine screenings for cancer and heart, kidney, liver, lung, or brain diseases. In addition, diagnostic or therapeutic procedures such as endoscopies, colonoscopies, angiograms, or biopsies abruptly stopped, resulting in a surge of non–COVID-19 medical disorders and mortality as reported in several articles across many specialties.²³ Going forward, in addition to COVID-19 morbidity and mortality, there is a significant likelihood of an increase in myriad medical disorders. The COVID-19 pandemic is obviously inflicting both direct and indirect casualties as it stretches into the next year and perhaps longer. The only hope for the community of nations is the rapid arrival of evidence-based treatments and vaccine(s).

Continue to: A progression of relentless stress

A progression of relentless stress

At the core of this pandemic is relentless stress. When it began in early 2020, the pandemic ignited an acute stress reaction due to the fear of death and the oddness of being isolated at home. Aggravating the acute stress was the realization that life as we knew it suddenly disappeared and all business or social activities had come to a screeching halt. It was almost surreal when streets usually bustling with human activity (such as Times Square in New York or Michigan Avenue in Chicago) became completely deserted and eerily silent. In addition, more stress was generated from watching television or scrolling through social media and being inundated with morbid and frightening news and updates about the number of individuals who became infected or died, and the official projections of tens of thousands or even hundreds of thousands of fatalities. Further intensifying the stress was hearing that there was a shortage of personal protective equipment (even masks), a lack of ventilators, and the absence of any medications to fight the overwhelming viral infection. Especially stressed were the front-line physicians and nurses, who heroically transcended their fears to save their patients’ lives. The sight of refrigerated trucks serving as temporary morgues outside hospital doors was chilling. The world became a macabre place where people died in hospitals without any relative to hold their hands or comfort them, and then were buried quickly without any formal funerals due to mandatory social distancing. The inability of families to grieve for their loved ones added another poignant layer of sadness and distress to the survivors who were unable to bid their loved ones goodbye. This was a jarring example of adding insult to injury.

With the protraction of the exceptional changes imposed by the pandemic, the acute stress reaction transmuted into posttraumatic stress disorder (PTSD) on a wide scale. Millions of previously healthy individuals began to succumb to the symptoms of PTSD (irritability, hypervigilance, intrusive thoughts, avoidance, insomnia, and bad dreams). The heaviest burden was inflicted on our patients, across all ages, with preexisting psychiatric conditions, who comprise approximately 25% of the population per the classic Epidemiological Catchment Area (ECA) study.²⁴ These vulnerable patients, whom we see in our clinics and hospitals every day, had a significant exacerbation of their psychopathology, including anxiety, depression, psychosis, binge eating disorder, obsessive-compulsive disorder, alcohol and substance use disorders, child abuse, and intimate partner violence.^25,26 The saving grace was the rapid adoption of telepsychiatry, which our psychiatric patients rapidly accepted. Many of them found it more convenient than dressing and driving and parking at the clinic. It also enabled psychiatrists to obtain useful collateral information from family members or partners.

If something good comes from this catastrophic social stress that emotionally hobbled the entire population, it would be the dilution of the stigma of mental illness because everyone has become more empathic due to their personal experience. Optimistically, this may also help expedite true health care parity for psychiatric brain disorders. And perhaps the government may see the need to train more psychiatrists and fund a higher number of residency stipends to all training programs.

Quo vadis COVID-19?

So, looking through the dense fog of the pandemic fatigue, what will 2021 bring us? Will waves of COVID-19 lead to pandemic exhaustion? Will the frayed public mental health care system be able to handle the surge of frayed nerves? Will social distancing intensify the widespread emotional disquietude? Will the children be able to manifest resilience and avoid disabling psychiatric disorders? Will the survivors of COVID-19 infections suffer from post–COVD-19 neuropsychiatric and other medical sequelae? Will efficacious therapies and vaccines emerge to blunt the spread of the virus? Will we all be able to gather in stadiums and arenas to enjoy sporting events, shows, and concerts? Will eating at our favorite restaurants become routine again? Will engaged couples be able to organize well-attended weddings and receptions? Will airplanes and hotels be fully booked again? Importantly, will all children and college students be able to resume their education in person and socialize ad lib? Will we be able to shed our masks and hug each other hello and goodbye? Will scientific journals and social media cover a wide array of topics again as before? Will the number of deaths dwindle to zero, and will we return to worrying mainly about the usual seasonal flu? Will everyone be able to leave home and go to work again?

I hope that the thick dust of this 2020 viral asteroid will settle in 2021, and that “normalcy” is eventually restored to our lives, allowing us to deal with other ongoing stresses such as social unrest and political hyperpartisanship.

Finally, 2020 is coming to an end, but the agony its viral pandemic inflicted on the entire world population will continue for a long time. And much as we would like to forget its damaging effects, it will surely be etched into our brains for the rest of our lives. The children who suffered the pain of the coronavirus disease 2019 (COVID-19) pandemic will endure its emotional scars for the rest of the 21st century.

Reading about the plagues of the past doesn’t come close to experiencing it and suffering through it. COVID-19 will continue to have ripple effects on every aspect of life on this planet, on individuals and on societies all over the world, especially on the biopsychosocial well-being of billions of humans around the globe.

Unprecedented disruptions

Think of the unprecedented disruptions inflicted by the trauma of the COVID-19 pandemic on our neural circuits. One of the wonders of the human brain is its continuous remodeling due to experiential neuroplasticity, and the formation of dendritic spines that immediately encode the memories of every experience. The turmoil of 2020 and its virulent pandemic will be forever etched into our collective brains, especially in our hippocampi and amygdalae. The impact on the developing brains of our children and grandchildren could be profound and may induce epigenetic changes that trigger psychopathology in the future.^1,2

As with the dinosaurs, the 2020 pandemic is like a “viral asteroid” that left devastation on our social fabric and psychological well-being in its wake. We now have deep empathy with our 1918 ancestors and their tribulations, although so far, in the United States the proportion of people infected with COVID-19 (3% as of mid-November 2020³) is dwarfed by the proportion infected with the influenza virus a century ago (30%). As of mid-November 2020, the number of global COVID-19 deaths (1.3 million³) was a tiny fraction of the 1918 influenza pandemic deaths (50 million worldwide and 675,000 in the United States⁴). Amazingly, researchers did not even know whether the killer germ was a virus or a bacterium until 1930, and it then took another 75 years to decode the genome of the influenza virus in 2005. In contrast, it took only a few short weeks to decode the genome of the virus that causes COVID-19 (severe acute respiratory syndrome-related coronavirus 2), and to begin developing multiple vaccines “at warp speed.” No vaccine or therapies were ever developed for victims of the 1918 pandemic.

An abundance of articles has been published about the pandemic since it ambushed us early in 2020, including many in Current Psychiatry.^5-21 But these publications don’t do justice to the emotional toll of living through the pandemic and witnessing its multi­farious repercussions (Table). It was truly bizarre and shocking for us to see our society and all its components literally come to a standstill, forcing the population to stop working, reducing us to simply “existing” inside our homes, with no socializing, traveling, or interacting. More unbearable than the sudden emptiness and paralysis was the unremitting fear, laced with a profound uncertainty of what was to come or when it would end.

Most psychiatrists are familiar with the Holmes and Rahe Stress Scale,²² which contains 43 life events that cumulatively can progressively increase the odds of physical illness. It is likely that most of the world’s population will score very high on the Holmes and Rahe Stress Scale, which would predict an increased risk of medical illness, even after the pandemic subsides.

Exacerbating the situation is that hospitals and clinics had to shut down most of their operations to focus their resources on treating patients with COVID-19 in ICUs. This halted all routine screenings for cancer and heart, kidney, liver, lung, or brain diseases. In addition, diagnostic or therapeutic procedures such as endoscopies, colonoscopies, angiograms, or biopsies abruptly stopped, resulting in a surge of non–COVID-19 medical disorders and mortality as reported in several articles across many specialties.²³ Going forward, in addition to COVID-19 morbidity and mortality, there is a significant likelihood of an increase in myriad medical disorders. The COVID-19 pandemic is obviously inflicting both direct and indirect casualties as it stretches into the next year and perhaps longer. The only hope for the community of nations is the rapid arrival of evidence-based treatments and vaccine(s).

Continue to: A progression of relentless stress

A progression of relentless stress

At the core of this pandemic is relentless stress. When it began in early 2020, the pandemic ignited an acute stress reaction due to the fear of death and the oddness of being isolated at home. Aggravating the acute stress was the realization that life as we knew it suddenly disappeared and all business or social activities had come to a screeching halt. It was almost surreal when streets usually bustling with human activity (such as Times Square in New York or Michigan Avenue in Chicago) became completely deserted and eerily silent. In addition, more stress was generated from watching television or scrolling through social media and being inundated with morbid and frightening news and updates about the number of individuals who became infected or died, and the official projections of tens of thousands or even hundreds of thousands of fatalities. Further intensifying the stress was hearing that there was a shortage of personal protective equipment (even masks), a lack of ventilators, and the absence of any medications to fight the overwhelming viral infection. Especially stressed were the front-line physicians and nurses, who heroically transcended their fears to save their patients’ lives. The sight of refrigerated trucks serving as temporary morgues outside hospital doors was chilling. The world became a macabre place where people died in hospitals without any relative to hold their hands or comfort them, and then were buried quickly without any formal funerals due to mandatory social distancing. The inability of families to grieve for their loved ones added another poignant layer of sadness and distress to the survivors who were unable to bid their loved ones goodbye. This was a jarring example of adding insult to injury.

With the protraction of the exceptional changes imposed by the pandemic, the acute stress reaction transmuted into posttraumatic stress disorder (PTSD) on a wide scale. Millions of previously healthy individuals began to succumb to the symptoms of PTSD (irritability, hypervigilance, intrusive thoughts, avoidance, insomnia, and bad dreams). The heaviest burden was inflicted on our patients, across all ages, with preexisting psychiatric conditions, who comprise approximately 25% of the population per the classic Epidemiological Catchment Area (ECA) study.²⁴ These vulnerable patients, whom we see in our clinics and hospitals every day, had a significant exacerbation of their psychopathology, including anxiety, depression, psychosis, binge eating disorder, obsessive-compulsive disorder, alcohol and substance use disorders, child abuse, and intimate partner violence.^25,26 The saving grace was the rapid adoption of telepsychiatry, which our psychiatric patients rapidly accepted. Many of them found it more convenient than dressing and driving and parking at the clinic. It also enabled psychiatrists to obtain useful collateral information from family members or partners.

If something good comes from this catastrophic social stress that emotionally hobbled the entire population, it would be the dilution of the stigma of mental illness because everyone has become more empathic due to their personal experience. Optimistically, this may also help expedite true health care parity for psychiatric brain disorders. And perhaps the government may see the need to train more psychiatrists and fund a higher number of residency stipends to all training programs.

Quo vadis COVID-19?

So, looking through the dense fog of the pandemic fatigue, what will 2021 bring us? Will waves of COVID-19 lead to pandemic exhaustion? Will the frayed public mental health care system be able to handle the surge of frayed nerves? Will social distancing intensify the widespread emotional disquietude? Will the children be able to manifest resilience and avoid disabling psychiatric disorders? Will the survivors of COVID-19 infections suffer from post–COVD-19 neuropsychiatric and other medical sequelae? Will efficacious therapies and vaccines emerge to blunt the spread of the virus? Will we all be able to gather in stadiums and arenas to enjoy sporting events, shows, and concerts? Will eating at our favorite restaurants become routine again? Will engaged couples be able to organize well-attended weddings and receptions? Will airplanes and hotels be fully booked again? Importantly, will all children and college students be able to resume their education in person and socialize ad lib? Will we be able to shed our masks and hug each other hello and goodbye? Will scientific journals and social media cover a wide array of topics again as before? Will the number of deaths dwindle to zero, and will we return to worrying mainly about the usual seasonal flu? Will everyone be able to leave home and go to work again?

I hope that the thick dust of this 2020 viral asteroid will settle in 2021, and that “normalcy” is eventually restored to our lives, allowing us to deal with other ongoing stresses such as social unrest and political hyperpartisanship.

Finally, 2020 is coming to an end, but the agony its viral pandemic inflicted on the entire world population will continue for a long time. And much as we would like to forget its damaging effects, it will surely be etched into our brains for the rest of our lives. The children who suffered the pain of the coronavirus disease 2019 (COVID-19) pandemic will endure its emotional scars for the rest of the 21st century.

Reading about the plagues of the past doesn’t come close to experiencing it and suffering through it. COVID-19 will continue to have ripple effects on every aspect of life on this planet, on individuals and on societies all over the world, especially on the biopsychosocial well-being of billions of humans around the globe.

Unprecedented disruptions

Think of the unprecedented disruptions inflicted by the trauma of the COVID-19 pandemic on our neural circuits. One of the wonders of the human brain is its continuous remodeling due to experiential neuroplasticity, and the formation of dendritic spines that immediately encode the memories of every experience. The turmoil of 2020 and its virulent pandemic will be forever etched into our collective brains, especially in our hippocampi and amygdalae. The impact on the developing brains of our children and grandchildren could be profound and may induce epigenetic changes that trigger psychopathology in the future.^1,2

As with the dinosaurs, the 2020 pandemic is like a “viral asteroid” that left devastation on our social fabric and psychological well-being in its wake. We now have deep empathy with our 1918 ancestors and their tribulations, although so far, in the United States the proportion of people infected with COVID-19 (3% as of mid-November 2020³) is dwarfed by the proportion infected with the influenza virus a century ago (30%). As of mid-November 2020, the number of global COVID-19 deaths (1.3 million³) was a tiny fraction of the 1918 influenza pandemic deaths (50 million worldwide and 675,000 in the United States⁴). Amazingly, researchers did not even know whether the killer germ was a virus or a bacterium until 1930, and it then took another 75 years to decode the genome of the influenza virus in 2005. In contrast, it took only a few short weeks to decode the genome of the virus that causes COVID-19 (severe acute respiratory syndrome-related coronavirus 2), and to begin developing multiple vaccines “at warp speed.” No vaccine or therapies were ever developed for victims of the 1918 pandemic.

An abundance of articles has been published about the pandemic since it ambushed us early in 2020, including many in Current Psychiatry.^5-21 But these publications don’t do justice to the emotional toll of living through the pandemic and witnessing its multi­farious repercussions (Table). It was truly bizarre and shocking for us to see our society and all its components literally come to a standstill, forcing the population to stop working, reducing us to simply “existing” inside our homes, with no socializing, traveling, or interacting. More unbearable than the sudden emptiness and paralysis was the unremitting fear, laced with a profound uncertainty of what was to come or when it would end.

Most psychiatrists are familiar with the Holmes and Rahe Stress Scale,²² which contains 43 life events that cumulatively can progressively increase the odds of physical illness. It is likely that most of the world’s population will score very high on the Holmes and Rahe Stress Scale, which would predict an increased risk of medical illness, even after the pandemic subsides.

Exacerbating the situation is that hospitals and clinics had to shut down most of their operations to focus their resources on treating patients with COVID-19 in ICUs. This halted all routine screenings for cancer and heart, kidney, liver, lung, or brain diseases. In addition, diagnostic or therapeutic procedures such as endoscopies, colonoscopies, angiograms, or biopsies abruptly stopped, resulting in a surge of non–COVID-19 medical disorders and mortality as reported in several articles across many specialties.²³ Going forward, in addition to COVID-19 morbidity and mortality, there is a significant likelihood of an increase in myriad medical disorders. The COVID-19 pandemic is obviously inflicting both direct and indirect casualties as it stretches into the next year and perhaps longer. The only hope for the community of nations is the rapid arrival of evidence-based treatments and vaccine(s).

Continue to: A progression of relentless stress

A progression of relentless stress

At the core of this pandemic is relentless stress. When it began in early 2020, the pandemic ignited an acute stress reaction due to the fear of death and the oddness of being isolated at home. Aggravating the acute stress was the realization that life as we knew it suddenly disappeared and all business or social activities had come to a screeching halt. It was almost surreal when streets usually bustling with human activity (such as Times Square in New York or Michigan Avenue in Chicago) became completely deserted and eerily silent. In addition, more stress was generated from watching television or scrolling through social media and being inundated with morbid and frightening news and updates about the number of individuals who became infected or died, and the official projections of tens of thousands or even hundreds of thousands of fatalities. Further intensifying the stress was hearing that there was a shortage of personal protective equipment (even masks), a lack of ventilators, and the absence of any medications to fight the overwhelming viral infection. Especially stressed were the front-line physicians and nurses, who heroically transcended their fears to save their patients’ lives. The sight of refrigerated trucks serving as temporary morgues outside hospital doors was chilling. The world became a macabre place where people died in hospitals without any relative to hold their hands or comfort them, and then were buried quickly without any formal funerals due to mandatory social distancing. The inability of families to grieve for their loved ones added another poignant layer of sadness and distress to the survivors who were unable to bid their loved ones goodbye. This was a jarring example of adding insult to injury.

With the protraction of the exceptional changes imposed by the pandemic, the acute stress reaction transmuted into posttraumatic stress disorder (PTSD) on a wide scale. Millions of previously healthy individuals began to succumb to the symptoms of PTSD (irritability, hypervigilance, intrusive thoughts, avoidance, insomnia, and bad dreams). The heaviest burden was inflicted on our patients, across all ages, with preexisting psychiatric conditions, who comprise approximately 25% of the population per the classic Epidemiological Catchment Area (ECA) study.²⁴ These vulnerable patients, whom we see in our clinics and hospitals every day, had a significant exacerbation of their psychopathology, including anxiety, depression, psychosis, binge eating disorder, obsessive-compulsive disorder, alcohol and substance use disorders, child abuse, and intimate partner violence.^25,26 The saving grace was the rapid adoption of telepsychiatry, which our psychiatric patients rapidly accepted. Many of them found it more convenient than dressing and driving and parking at the clinic. It also enabled psychiatrists to obtain useful collateral information from family members or partners.

If something good comes from this catastrophic social stress that emotionally hobbled the entire population, it would be the dilution of the stigma of mental illness because everyone has become more empathic due to their personal experience. Optimistically, this may also help expedite true health care parity for psychiatric brain disorders. And perhaps the government may see the need to train more psychiatrists and fund a higher number of residency stipends to all training programs.

Quo vadis COVID-19?

So, looking through the dense fog of the pandemic fatigue, what will 2021 bring us? Will waves of COVID-19 lead to pandemic exhaustion? Will the frayed public mental health care system be able to handle the surge of frayed nerves? Will social distancing intensify the widespread emotional disquietude? Will the children be able to manifest resilience and avoid disabling psychiatric disorders? Will the survivors of COVID-19 infections suffer from post–COVD-19 neuropsychiatric and other medical sequelae? Will efficacious therapies and vaccines emerge to blunt the spread of the virus? Will we all be able to gather in stadiums and arenas to enjoy sporting events, shows, and concerts? Will eating at our favorite restaurants become routine again? Will engaged couples be able to organize well-attended weddings and receptions? Will airplanes and hotels be fully booked again? Importantly, will all children and college students be able to resume their education in person and socialize ad lib? Will we be able to shed our masks and hug each other hello and goodbye? Will scientific journals and social media cover a wide array of topics again as before? Will the number of deaths dwindle to zero, and will we return to worrying mainly about the usual seasonal flu? Will everyone be able to leave home and go to work again?

I hope that the thick dust of this 2020 viral asteroid will settle in 2021, and that “normalcy” is eventually restored to our lives, allowing us to deal with other ongoing stresses such as social unrest and political hyperpartisanship.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

I am a retired advanced practice psychiatric nurse who has lived and worked on “both sides of the door.” This wording is paraphrased from psychologist and therapist Lauren Slater, PhD, who wrote about a time she went to McLean Hospital in Belmont, Massachusetts, as a therapist after staying there as a patient years earlier: “And now I am standing on the other—the wrong, I mean the right side of the door and I ring the buzzer.”¹ Here I tell my story of the physical and emotional effects of my mental illness and treatment.

Onset of bipolar disorder. My bipolar illness started with a bout of depression in 1963 at age 13, which resulted in a low-key summer of often staying inside. I received no medication, and no one sent me for evaluation. In the fall, I went back to school and finished the year without incident. I continued as a quiet, shy kid through high school in the late 1960s. In my senior year, I decided to take an overload of difficult courses and run on the varsity cross-country team. The amount and intensity of these activities were too much. This resulted in my first manic episode, which started during a weekend visit to a college I hoped to attend. I became excitable, grandiose, and had delusions. A day later, I returned home, and my parents had me admitted to a psychiatric hospital, where I remained for 3 months.

At first, my diagnosis was unclear, and initially no one considered what at the time was called manic depression. At that point, I was unaware of my extensive family psychiatric history. My pharmacologic treatment consisted of chlorpromazine, trifluoperazine, and procyclidine. I returned home just before Christmas and barely finished my senior year of high school. A good college accepted me. But during the orientation, I was asked to leave because I experienced a second manic episode. After 4 more psychiatric hospitalizations, I finally stabilized.

During one of my hospitalizations, I had the good fortune to be interviewed by Dr. Thomas Detre. During this interview, I talked expansively about Don Quixote, Aldonza, and Sancho Panza. Dr. Detre diagnosed me with manic depression, and suggested that I see Dr. Christiaan van der Velde, who was researching lithium carbonate.² In 1970, I was hospitalized at Norwich State Hospital in Preston, Connecticut and was started on lithium, even though it had not yet been FDA-approved. I responded well to lithium monotherapy.

An extensive family history. Having bipolar disorder was not something I would discuss with others because I felt ashamed. I commonly hid my medication during college, especially from my roommates or other friends. By then, I had learned a little about my family’s psychiatric history, but I knew few specifics. Over time, I became aware of a dense familial cluster of affective illness going back several generations. My maternal grandmother was hospitalized for depression in 1921 after her husband suddenly died during her fourth pregnancy. She became bereft and suicidal because she had no one to support her 4 children. During my grandmother’s hospitalization, her sister and sister’s husband took care of her children. My grandmother remained hospitalized until she died in 1943. At that time, no medications were available to treat her illness. Over the next 2 generations, 2 of her 4 children and 6 of her 12 grandchildren (including me) developed bipolar disorder.

A career and family. In 1970, I started to work as a nursing assistant, then as a nursing technician for 1.5 years in a specialty hospital in New England. In 1973, I began nursing school at a junior college. I received my RN in 1975, a BS in nursing in 1979, and an MS in psychiatric nursing in 1982. I worked steadily as a psychiatric nurse in both inpatient and outpatient settings from 1975 until I retired in 2019.

In the early 1980s, I married my first wife and had 2 wonderful children. During our courtship in 1981 and 1982, I became hypomanic, which perhaps made me more outgoing and sociable. In 1985, after my father required open heart surgery, I had a manic episode that lasted 1 week. Over the next 20 years, although I was not happy with my marriage, I remained euthymic and productive at work. My marriage ended in 2012.

Continue to: By the end of 2012...

By the end of 2012, I had been taking lithium continuously for 42 years. My laboratory tests showed peak lithium levels between 0.6 and 1.2 mmol/L. I remained otherwise healthy, as demonstrated by annual physical exams and laboratory test results. In 2015, I developed an increase in my blood pressure and my primary care physician (PCP) prescribed oral lisinopril, initially 10 mg/d, and later 10 mg twice daily. My blood pressure improved and ranged from 120/74 to 130/82 mm Hg.

Hyperparathyroidism. By 2016, my psychiatrist, PCP, and nephrologist all urged me to consider parathyroid surgery.^3-5 Hypercalcemia and hyperparathyroidism caused the most worry. Laboratory tests indicated calcium 11.2 mg/dL, parathyroid hormone (PTH) 88 pg/mL, estimated glomerular filtration rate (eGFR) 59 mL/min, and thyroid-stimulating hormone (TSH) 0.78 mIU/L. Electrocardiographysometimes showed a slight QT elongation. A right bundle branch block, which was first noted in 2015, continued. Due to my elevated calcium levels, I eliminated most calcium from my diet. My psychiatrist began to speak more strongly of parathyroid surgery. I then consulted a senior endocrinologist and a senior nephrologist, who each recommended parathyroid surgery.

I remarried in July 2016, and we moved to a different area of the country. My second wife became a stabilizing force for me. My new PCP, however, found elevated high-density lipoproteins during a routine physical examination, and started me on simvastatin, 10 mg/d. My calcium and PTH levels continued to be elevated. My PCP, nephrologist, therapist, and wife urged me to proceed with the parathyroidectomy. After a short period of watchful waiting and a second consultation with a nephrologist, I agreed to schedule a subtotal parathyroidectomy.

Surgery. In spring 2017, I began preparation for parathyroidectomy. At the time, my lithium carbonate dose was 600 mg/d, alternating with 900 mg/d. My peak level of lithium was 0.6 mmol/L. Lisinopril is synergistic, which allowed me to take a smaller effective dose of lithium.

My parathyroid surgery occurred on June 28, 2017 at Norman Parathyroid Center in Tampa, Florida.⁶ The surgeon recorded my parathyroid glands as 136, 602, and 348 units using a measure developed at Norman Parathyroid Center. No reading was given for my fourth parathyroid gland, which they did not remove. Following the surgery, I resumed my previous functions, including employment as a visiting nurse. I initially took calcium supplements after surgery, and my lithium dose was reduced to 300 mg orally, twice daily, which I have continued. I have remained euthymic. On August 3, 2017 my laboratory workup showed an eGFR of 64 mL/min, calcium 10.0 mg/dL, and PTH 17 pg/mL. Vitamin D25 OH 33, glucose, BUN/Cr, electrolytes, complete blood count, and albumin were all within normal limits. Repeat bloodwork on September 19, 2017 showed Ca⁺⁺ 10.1 mg/dL and PTH 18 pg/mL. Nine months after the surgery, I showed an incredibly positive physical and mental response, which has continued to this day.

Continue to: Clinical implications

Clinical implications. This is a single case study. However, it is important for clinicians treating patients with lithium carbonate to regularly order laboratory testing, including for lithium levels, PTH, and calcium, to detect early signs of complications from treatment, including hyperparathyroidism and hypercalcemia.⁷ These levels could be obtained every 6 months. If a patient’s PTH levels are >70 pg/mL and calcium levels are >11.0 mg/dL, it would be prudent to refer him/her for further medical evaluation. Additionally, it would be helpful to counsel the patient about considering alternative medication and adjunct mental health treatment. At some future point, it could be useful for the clinician and his/her patient to explore the idea of parathyroid surgery.

In addition to chronic lithium use, other causes of hyperparathyroidism include an adenoma on a gland, hyperplasia of ≥2 parathyroid glands, a malignant tumor, severe calcium deficiency, severe vitamin D deficiency, chronic renal failure, and (rarely) an inherited gene that causes hyperparathyroidism.

How I’m doing today. Currently, I am euthymic and in a happy marriage. My laboratory workup in May 2020 included glucose 107 mg/dL, Ca⁺⁺ 9.5 mg/dL, eGFR 61 mL/min, PTH 32 pg/mL, lithium 0.3 mmol/L (300 mg twice daily), and TSH 1.79 mIU/L. A comprehensive metabolic panel, complete blood count, and lipid panel were all within normal limits.

I am fortunate to continue having excellent care provided by my PCP, nephrologist, urologist, and psychiatric APRN. Together with these wonderful professionals, I have been able to maintain my physical and mental health.

Acknowledgment: I gratefully acknowledge the help and skills of Robin Scharak and Gary Blake for providing some of the editing on this article.

Bill Greenberg MS, RN, APRN
Delray Beach, Florida

I am a retired advanced practice psychiatric nurse who has lived and worked on “both sides of the door.” This wording is paraphrased from psychologist and therapist Lauren Slater, PhD, who wrote about a time she went to McLean Hospital in Belmont, Massachusetts, as a therapist after staying there as a patient years earlier: “And now I am standing on the other—the wrong, I mean the right side of the door and I ring the buzzer.”¹ Here I tell my story of the physical and emotional effects of my mental illness and treatment.

Onset of bipolar disorder. My bipolar illness started with a bout of depression in 1963 at age 13, which resulted in a low-key summer of often staying inside. I received no medication, and no one sent me for evaluation. In the fall, I went back to school and finished the year without incident. I continued as a quiet, shy kid through high school in the late 1960s. In my senior year, I decided to take an overload of difficult courses and run on the varsity cross-country team. The amount and intensity of these activities were too much. This resulted in my first manic episode, which started during a weekend visit to a college I hoped to attend. I became excitable, grandiose, and had delusions. A day later, I returned home, and my parents had me admitted to a psychiatric hospital, where I remained for 3 months.

At first, my diagnosis was unclear, and initially no one considered what at the time was called manic depression. At that point, I was unaware of my extensive family psychiatric history. My pharmacologic treatment consisted of chlorpromazine, trifluoperazine, and procyclidine. I returned home just before Christmas and barely finished my senior year of high school. A good college accepted me. But during the orientation, I was asked to leave because I experienced a second manic episode. After 4 more psychiatric hospitalizations, I finally stabilized.

During one of my hospitalizations, I had the good fortune to be interviewed by Dr. Thomas Detre. During this interview, I talked expansively about Don Quixote, Aldonza, and Sancho Panza. Dr. Detre diagnosed me with manic depression, and suggested that I see Dr. Christiaan van der Velde, who was researching lithium carbonate.² In 1970, I was hospitalized at Norwich State Hospital in Preston, Connecticut and was started on lithium, even though it had not yet been FDA-approved. I responded well to lithium monotherapy.

An extensive family history. Having bipolar disorder was not something I would discuss with others because I felt ashamed. I commonly hid my medication during college, especially from my roommates or other friends. By then, I had learned a little about my family’s psychiatric history, but I knew few specifics. Over time, I became aware of a dense familial cluster of affective illness going back several generations. My maternal grandmother was hospitalized for depression in 1921 after her husband suddenly died during her fourth pregnancy. She became bereft and suicidal because she had no one to support her 4 children. During my grandmother’s hospitalization, her sister and sister’s husband took care of her children. My grandmother remained hospitalized until she died in 1943. At that time, no medications were available to treat her illness. Over the next 2 generations, 2 of her 4 children and 6 of her 12 grandchildren (including me) developed bipolar disorder.

A career and family. In 1970, I started to work as a nursing assistant, then as a nursing technician for 1.5 years in a specialty hospital in New England. In 1973, I began nursing school at a junior college. I received my RN in 1975, a BS in nursing in 1979, and an MS in psychiatric nursing in 1982. I worked steadily as a psychiatric nurse in both inpatient and outpatient settings from 1975 until I retired in 2019.

In the early 1980s, I married my first wife and had 2 wonderful children. During our courtship in 1981 and 1982, I became hypomanic, which perhaps made me more outgoing and sociable. In 1985, after my father required open heart surgery, I had a manic episode that lasted 1 week. Over the next 20 years, although I was not happy with my marriage, I remained euthymic and productive at work. My marriage ended in 2012.

Continue to: By the end of 2012...

By the end of 2012, I had been taking lithium continuously for 42 years. My laboratory tests showed peak lithium levels between 0.6 and 1.2 mmol/L. I remained otherwise healthy, as demonstrated by annual physical exams and laboratory test results. In 2015, I developed an increase in my blood pressure and my primary care physician (PCP) prescribed oral lisinopril, initially 10 mg/d, and later 10 mg twice daily. My blood pressure improved and ranged from 120/74 to 130/82 mm Hg.

Hyperparathyroidism. By 2016, my psychiatrist, PCP, and nephrologist all urged me to consider parathyroid surgery.^3-5 Hypercalcemia and hyperparathyroidism caused the most worry. Laboratory tests indicated calcium 11.2 mg/dL, parathyroid hormone (PTH) 88 pg/mL, estimated glomerular filtration rate (eGFR) 59 mL/min, and thyroid-stimulating hormone (TSH) 0.78 mIU/L. Electrocardiographysometimes showed a slight QT elongation. A right bundle branch block, which was first noted in 2015, continued. Due to my elevated calcium levels, I eliminated most calcium from my diet. My psychiatrist began to speak more strongly of parathyroid surgery. I then consulted a senior endocrinologist and a senior nephrologist, who each recommended parathyroid surgery.

I remarried in July 2016, and we moved to a different area of the country. My second wife became a stabilizing force for me. My new PCP, however, found elevated high-density lipoproteins during a routine physical examination, and started me on simvastatin, 10 mg/d. My calcium and PTH levels continued to be elevated. My PCP, nephrologist, therapist, and wife urged me to proceed with the parathyroidectomy. After a short period of watchful waiting and a second consultation with a nephrologist, I agreed to schedule a subtotal parathyroidectomy.

Surgery. In spring 2017, I began preparation for parathyroidectomy. At the time, my lithium carbonate dose was 600 mg/d, alternating with 900 mg/d. My peak level of lithium was 0.6 mmol/L. Lisinopril is synergistic, which allowed me to take a smaller effective dose of lithium.

My parathyroid surgery occurred on June 28, 2017 at Norman Parathyroid Center in Tampa, Florida.⁶ The surgeon recorded my parathyroid glands as 136, 602, and 348 units using a measure developed at Norman Parathyroid Center. No reading was given for my fourth parathyroid gland, which they did not remove. Following the surgery, I resumed my previous functions, including employment as a visiting nurse. I initially took calcium supplements after surgery, and my lithium dose was reduced to 300 mg orally, twice daily, which I have continued. I have remained euthymic. On August 3, 2017 my laboratory workup showed an eGFR of 64 mL/min, calcium 10.0 mg/dL, and PTH 17 pg/mL. Vitamin D25 OH 33, glucose, BUN/Cr, electrolytes, complete blood count, and albumin were all within normal limits. Repeat bloodwork on September 19, 2017 showed Ca⁺⁺ 10.1 mg/dL and PTH 18 pg/mL. Nine months after the surgery, I showed an incredibly positive physical and mental response, which has continued to this day.

Continue to: Clinical implications

Clinical implications. This is a single case study. However, it is important for clinicians treating patients with lithium carbonate to regularly order laboratory testing, including for lithium levels, PTH, and calcium, to detect early signs of complications from treatment, including hyperparathyroidism and hypercalcemia.⁷ These levels could be obtained every 6 months. If a patient’s PTH levels are >70 pg/mL and calcium levels are >11.0 mg/dL, it would be prudent to refer him/her for further medical evaluation. Additionally, it would be helpful to counsel the patient about considering alternative medication and adjunct mental health treatment. At some future point, it could be useful for the clinician and his/her patient to explore the idea of parathyroid surgery.

In addition to chronic lithium use, other causes of hyperparathyroidism include an adenoma on a gland, hyperplasia of ≥2 parathyroid glands, a malignant tumor, severe calcium deficiency, severe vitamin D deficiency, chronic renal failure, and (rarely) an inherited gene that causes hyperparathyroidism.

How I’m doing today. Currently, I am euthymic and in a happy marriage. My laboratory workup in May 2020 included glucose 107 mg/dL, Ca⁺⁺ 9.5 mg/dL, eGFR 61 mL/min, PTH 32 pg/mL, lithium 0.3 mmol/L (300 mg twice daily), and TSH 1.79 mIU/L. A comprehensive metabolic panel, complete blood count, and lipid panel were all within normal limits.

I am fortunate to continue having excellent care provided by my PCP, nephrologist, urologist, and psychiatric APRN. Together with these wonderful professionals, I have been able to maintain my physical and mental health.

Acknowledgment: I gratefully acknowledge the help and skills of Robin Scharak and Gary Blake for providing some of the editing on this article.

Bill Greenberg MS, RN, APRN
Delray Beach, Florida

I am a retired advanced practice psychiatric nurse who has lived and worked on “both sides of the door.” This wording is paraphrased from psychologist and therapist Lauren Slater, PhD, who wrote about a time she went to McLean Hospital in Belmont, Massachusetts, as a therapist after staying there as a patient years earlier: “And now I am standing on the other—the wrong, I mean the right side of the door and I ring the buzzer.”¹ Here I tell my story of the physical and emotional effects of my mental illness and treatment.

Onset of bipolar disorder. My bipolar illness started with a bout of depression in 1963 at age 13, which resulted in a low-key summer of often staying inside. I received no medication, and no one sent me for evaluation. In the fall, I went back to school and finished the year without incident. I continued as a quiet, shy kid through high school in the late 1960s. In my senior year, I decided to take an overload of difficult courses and run on the varsity cross-country team. The amount and intensity of these activities were too much. This resulted in my first manic episode, which started during a weekend visit to a college I hoped to attend. I became excitable, grandiose, and had delusions. A day later, I returned home, and my parents had me admitted to a psychiatric hospital, where I remained for 3 months.

At first, my diagnosis was unclear, and initially no one considered what at the time was called manic depression. At that point, I was unaware of my extensive family psychiatric history. My pharmacologic treatment consisted of chlorpromazine, trifluoperazine, and procyclidine. I returned home just before Christmas and barely finished my senior year of high school. A good college accepted me. But during the orientation, I was asked to leave because I experienced a second manic episode. After 4 more psychiatric hospitalizations, I finally stabilized.

During one of my hospitalizations, I had the good fortune to be interviewed by Dr. Thomas Detre. During this interview, I talked expansively about Don Quixote, Aldonza, and Sancho Panza. Dr. Detre diagnosed me with manic depression, and suggested that I see Dr. Christiaan van der Velde, who was researching lithium carbonate.² In 1970, I was hospitalized at Norwich State Hospital in Preston, Connecticut and was started on lithium, even though it had not yet been FDA-approved. I responded well to lithium monotherapy.

An extensive family history. Having bipolar disorder was not something I would discuss with others because I felt ashamed. I commonly hid my medication during college, especially from my roommates or other friends. By then, I had learned a little about my family’s psychiatric history, but I knew few specifics. Over time, I became aware of a dense familial cluster of affective illness going back several generations. My maternal grandmother was hospitalized for depression in 1921 after her husband suddenly died during her fourth pregnancy. She became bereft and suicidal because she had no one to support her 4 children. During my grandmother’s hospitalization, her sister and sister’s husband took care of her children. My grandmother remained hospitalized until she died in 1943. At that time, no medications were available to treat her illness. Over the next 2 generations, 2 of her 4 children and 6 of her 12 grandchildren (including me) developed bipolar disorder.

A career and family. In 1970, I started to work as a nursing assistant, then as a nursing technician for 1.5 years in a specialty hospital in New England. In 1973, I began nursing school at a junior college. I received my RN in 1975, a BS in nursing in 1979, and an MS in psychiatric nursing in 1982. I worked steadily as a psychiatric nurse in both inpatient and outpatient settings from 1975 until I retired in 2019.

In the early 1980s, I married my first wife and had 2 wonderful children. During our courtship in 1981 and 1982, I became hypomanic, which perhaps made me more outgoing and sociable. In 1985, after my father required open heart surgery, I had a manic episode that lasted 1 week. Over the next 20 years, although I was not happy with my marriage, I remained euthymic and productive at work. My marriage ended in 2012.

Continue to: By the end of 2012...

By the end of 2012, I had been taking lithium continuously for 42 years. My laboratory tests showed peak lithium levels between 0.6 and 1.2 mmol/L. I remained otherwise healthy, as demonstrated by annual physical exams and laboratory test results. In 2015, I developed an increase in my blood pressure and my primary care physician (PCP) prescribed oral lisinopril, initially 10 mg/d, and later 10 mg twice daily. My blood pressure improved and ranged from 120/74 to 130/82 mm Hg.

Hyperparathyroidism. By 2016, my psychiatrist, PCP, and nephrologist all urged me to consider parathyroid surgery.^3-5 Hypercalcemia and hyperparathyroidism caused the most worry. Laboratory tests indicated calcium 11.2 mg/dL, parathyroid hormone (PTH) 88 pg/mL, estimated glomerular filtration rate (eGFR) 59 mL/min, and thyroid-stimulating hormone (TSH) 0.78 mIU/L. Electrocardiographysometimes showed a slight QT elongation. A right bundle branch block, which was first noted in 2015, continued. Due to my elevated calcium levels, I eliminated most calcium from my diet. My psychiatrist began to speak more strongly of parathyroid surgery. I then consulted a senior endocrinologist and a senior nephrologist, who each recommended parathyroid surgery.

I remarried in July 2016, and we moved to a different area of the country. My second wife became a stabilizing force for me. My new PCP, however, found elevated high-density lipoproteins during a routine physical examination, and started me on simvastatin, 10 mg/d. My calcium and PTH levels continued to be elevated. My PCP, nephrologist, therapist, and wife urged me to proceed with the parathyroidectomy. After a short period of watchful waiting and a second consultation with a nephrologist, I agreed to schedule a subtotal parathyroidectomy.

Surgery. In spring 2017, I began preparation for parathyroidectomy. At the time, my lithium carbonate dose was 600 mg/d, alternating with 900 mg/d. My peak level of lithium was 0.6 mmol/L. Lisinopril is synergistic, which allowed me to take a smaller effective dose of lithium.

My parathyroid surgery occurred on June 28, 2017 at Norman Parathyroid Center in Tampa, Florida.⁶ The surgeon recorded my parathyroid glands as 136, 602, and 348 units using a measure developed at Norman Parathyroid Center. No reading was given for my fourth parathyroid gland, which they did not remove. Following the surgery, I resumed my previous functions, including employment as a visiting nurse. I initially took calcium supplements after surgery, and my lithium dose was reduced to 300 mg orally, twice daily, which I have continued. I have remained euthymic. On August 3, 2017 my laboratory workup showed an eGFR of 64 mL/min, calcium 10.0 mg/dL, and PTH 17 pg/mL. Vitamin D25 OH 33, glucose, BUN/Cr, electrolytes, complete blood count, and albumin were all within normal limits. Repeat bloodwork on September 19, 2017 showed Ca⁺⁺ 10.1 mg/dL and PTH 18 pg/mL. Nine months after the surgery, I showed an incredibly positive physical and mental response, which has continued to this day.

Continue to: Clinical implications

Clinical implications. This is a single case study. However, it is important for clinicians treating patients with lithium carbonate to regularly order laboratory testing, including for lithium levels, PTH, and calcium, to detect early signs of complications from treatment, including hyperparathyroidism and hypercalcemia.⁷ These levels could be obtained every 6 months. If a patient’s PTH levels are >70 pg/mL and calcium levels are >11.0 mg/dL, it would be prudent to refer him/her for further medical evaluation. Additionally, it would be helpful to counsel the patient about considering alternative medication and adjunct mental health treatment. At some future point, it could be useful for the clinician and his/her patient to explore the idea of parathyroid surgery.

In addition to chronic lithium use, other causes of hyperparathyroidism include an adenoma on a gland, hyperplasia of ≥2 parathyroid glands, a malignant tumor, severe calcium deficiency, severe vitamin D deficiency, chronic renal failure, and (rarely) an inherited gene that causes hyperparathyroidism.

How I’m doing today. Currently, I am euthymic and in a happy marriage. My laboratory workup in May 2020 included glucose 107 mg/dL, Ca⁺⁺ 9.5 mg/dL, eGFR 61 mL/min, PTH 32 pg/mL, lithium 0.3 mmol/L (300 mg twice daily), and TSH 1.79 mIU/L. A comprehensive metabolic panel, complete blood count, and lipid panel were all within normal limits.

I am fortunate to continue having excellent care provided by my PCP, nephrologist, urologist, and psychiatric APRN. Together with these wonderful professionals, I have been able to maintain my physical and mental health.

Acknowledgment: I gratefully acknowledge the help and skills of Robin Scharak and Gary Blake for providing some of the editing on this article.

Bill Greenberg MS, RN, APRN
Delray Beach, Florida