Ob.Gyn. News

Many countries have “a long way to go” toward meeting the World Health Organization’s target for human papilloma virus (HPV) vaccination, according to researchers.

The WHO’s goal is to have HPV vaccines delivered to 90% of all adolescent girls by 2030, part of the organization’s larger goal to “eliminate” cervical cancer, or reduce the annual incidence of cervical cancer to below 4 cases per 100,000 people globally.

Laia Bruni, MD, PhD, of Catalan Institute of Oncology in Barcelona, and colleagues outlined the progress made thus far toward reaching the WHO’s goals in an article published in Preventive Medicine.

The authors noted that cervical cancer caused by HPV is a “major public health problem, especially in low- and middle-income countries (LMIC).”

However, vaccines against HPV have been available since 2006 and have been recommended by the WHO since 2009.

HPV vaccines have been introduced into many national immunization schedules. Among the 194 WHO member states, 107 (55%) had introduced HPV vaccination as of June 2020, according to estimates from the WHO and the United Nations International Children’s Emergency Fund (UNICEF).

Still, vaccine introduction and coverages are suboptimal, according to several studies and international agencies.

In their article, Dr. Bruni and colleagues describe the mid-2020 status of HPV vaccine introduction, based on WHO/UNICEF estimates of national HPV immunization coverage from 2010 to 2019.
 

HPV vaccination by region

The Americas and Europe are by far the WHO regions with the highest rates of HPV vaccination, with 85% and 77% of their countries, respectively, having already introduced HPV vaccination, either partially or nationwide.

In 2019, a record number of introductions, 16, were reported, mostly in LMICs where access has been limited. In prior years, the average had been a relatively steady 7-8 introductions per year.

The percentage of high-income countries (HICs) that have introduced HPV vaccination exceeds 80%. LMICs started introducing HPV vaccination later and at a slower pace, compared with HICs. By the end of 2019, only 41% of LMICs had introduced vaccination. However, of the new introductions in 2019, 87% were in LMICs.

In 2019, the average performance coverage for HPV vaccination programs in 99 countries (both HICs and LMICs) was around 67% for the first vaccine dose and 53% for the final dose.

Median performance coverage was higher in LMICs than in HICs for the first dose (80% and 72%, respectively), but mean dropout rates were higher in LMICs than in HICs (18% and 11%, respectively).

Coverage of more than 90% was achieved for the last dose in only five countries (6%). Twenty-two countries (21%) achieved coverages of 75% or higher, while 35 countries (40%) had final dose coverages of 50% or less.

Global coverage of the final HPV vaccine dose (weighted by population size) was estimated at 15%. According to the authors, that low percentage can be explained by the fact that many of the most populous countries have either not yet introduced HPV vaccination or have low performance.

The countries with highest cervical cancer burden have had limited secondary prevention and have been less likely to provide access to vaccination, the authors noted. However, this trend appears to be reversing, with 14 new LMICs providing HPV vaccination in 2019.
 

HPV vaccination by sex

By 2019, almost a third of the 107 HPV vaccination programs (n = 33) were “gender neutral,” with girls and boys receiving HPV vaccines. Generally, LMICs targeted younger girls (9-10 years) compared with HICs (11-13 years).

Dr. Bruni and colleagues estimated that 15% of girls and 4% of boys were vaccinated globally with the full course of vaccine. At least one dose was received by 20% of girls and 5% of boys.

From 2010 to 2019, HPV vaccination rates in HICs rose from 42% in girls and 0% in boys to 88% and 44%, respectively. In LMICs, over the same period, rates rose from 4% in girls and 0% in boys to 40% and 5%, respectively.
 

Obstacles and the path forward

The COVID-19 pandemic has halted HPV vaccine delivery in the majority of countries, Dr. Bruni and colleagues noted. About 70 countries had reported program interruptions by August 2020, and delays to HPV vaccine introductions were anticipated for other countries.

An economic downturn could have further far-reaching effects on plans to introduce HPV vaccines, Dr. Bruni and colleagues observed.

While meeting the 2030 target will be challenging, the authors noted that, in every geographic area, some programs are meeting the 90% target.

“HPV national programs should aim to get 90+% of girls vaccinated before the age of 15,” Dr. Bruni said in an interview. “This is a feasible goal, and some countries have succeeded, such as Norway and Rwanda. Average performance, however, is around 55%, and that shows that it is not an easy task.”

Dr. Bruni underscored the four main actions that should be taken to achieve 90% coverage of HPV vaccination, as outlined in the WHO cervical cancer elimination strategy:

• Secure sufficient and affordable HPV vaccines.
• Increase the quality and coverage of vaccination.
• Improve communication and social mobilization.
• Innovate to improve efficiency of vaccine delivery.

“Addressing vaccine hesitancy adequately is one of the biggest challenges we face, especially for the HPV vaccine,” Dr. Bruni said. “As the WHO document states, understanding social, cultural, societal, and other barriers affecting acceptance and uptake of the vaccine will be critical for overcoming vaccine hesitancy and countering misinformation.”

This research was funded by a grant from Instituto de Salud Carlos III and various other grants. Dr. Bruni and coauthors said they have no relevant disclosures.

Many countries have “a long way to go” toward meeting the World Health Organization’s target for human papilloma virus (HPV) vaccination, according to researchers.

The WHO’s goal is to have HPV vaccines delivered to 90% of all adolescent girls by 2030, part of the organization’s larger goal to “eliminate” cervical cancer, or reduce the annual incidence of cervical cancer to below 4 cases per 100,000 people globally.

Laia Bruni, MD, PhD, of Catalan Institute of Oncology in Barcelona, and colleagues outlined the progress made thus far toward reaching the WHO’s goals in an article published in Preventive Medicine.

The authors noted that cervical cancer caused by HPV is a “major public health problem, especially in low- and middle-income countries (LMIC).”

However, vaccines against HPV have been available since 2006 and have been recommended by the WHO since 2009.

HPV vaccines have been introduced into many national immunization schedules. Among the 194 WHO member states, 107 (55%) had introduced HPV vaccination as of June 2020, according to estimates from the WHO and the United Nations International Children’s Emergency Fund (UNICEF).

Still, vaccine introduction and coverages are suboptimal, according to several studies and international agencies.

In their article, Dr. Bruni and colleagues describe the mid-2020 status of HPV vaccine introduction, based on WHO/UNICEF estimates of national HPV immunization coverage from 2010 to 2019.
 

HPV vaccination by region

The Americas and Europe are by far the WHO regions with the highest rates of HPV vaccination, with 85% and 77% of their countries, respectively, having already introduced HPV vaccination, either partially or nationwide.

In 2019, a record number of introductions, 16, were reported, mostly in LMICs where access has been limited. In prior years, the average had been a relatively steady 7-8 introductions per year.

The percentage of high-income countries (HICs) that have introduced HPV vaccination exceeds 80%. LMICs started introducing HPV vaccination later and at a slower pace, compared with HICs. By the end of 2019, only 41% of LMICs had introduced vaccination. However, of the new introductions in 2019, 87% were in LMICs.

In 2019, the average performance coverage for HPV vaccination programs in 99 countries (both HICs and LMICs) was around 67% for the first vaccine dose and 53% for the final dose.

Median performance coverage was higher in LMICs than in HICs for the first dose (80% and 72%, respectively), but mean dropout rates were higher in LMICs than in HICs (18% and 11%, respectively).

Coverage of more than 90% was achieved for the last dose in only five countries (6%). Twenty-two countries (21%) achieved coverages of 75% or higher, while 35 countries (40%) had final dose coverages of 50% or less.

Global coverage of the final HPV vaccine dose (weighted by population size) was estimated at 15%. According to the authors, that low percentage can be explained by the fact that many of the most populous countries have either not yet introduced HPV vaccination or have low performance.

The countries with highest cervical cancer burden have had limited secondary prevention and have been less likely to provide access to vaccination, the authors noted. However, this trend appears to be reversing, with 14 new LMICs providing HPV vaccination in 2019.
 

HPV vaccination by sex

By 2019, almost a third of the 107 HPV vaccination programs (n = 33) were “gender neutral,” with girls and boys receiving HPV vaccines. Generally, LMICs targeted younger girls (9-10 years) compared with HICs (11-13 years).

Dr. Bruni and colleagues estimated that 15% of girls and 4% of boys were vaccinated globally with the full course of vaccine. At least one dose was received by 20% of girls and 5% of boys.

From 2010 to 2019, HPV vaccination rates in HICs rose from 42% in girls and 0% in boys to 88% and 44%, respectively. In LMICs, over the same period, rates rose from 4% in girls and 0% in boys to 40% and 5%, respectively.
 

Obstacles and the path forward

The COVID-19 pandemic has halted HPV vaccine delivery in the majority of countries, Dr. Bruni and colleagues noted. About 70 countries had reported program interruptions by August 2020, and delays to HPV vaccine introductions were anticipated for other countries.

An economic downturn could have further far-reaching effects on plans to introduce HPV vaccines, Dr. Bruni and colleagues observed.

While meeting the 2030 target will be challenging, the authors noted that, in every geographic area, some programs are meeting the 90% target.

“HPV national programs should aim to get 90+% of girls vaccinated before the age of 15,” Dr. Bruni said in an interview. “This is a feasible goal, and some countries have succeeded, such as Norway and Rwanda. Average performance, however, is around 55%, and that shows that it is not an easy task.”

Dr. Bruni underscored the four main actions that should be taken to achieve 90% coverage of HPV vaccination, as outlined in the WHO cervical cancer elimination strategy:

• Secure sufficient and affordable HPV vaccines.
• Increase the quality and coverage of vaccination.
• Improve communication and social mobilization.
• Innovate to improve efficiency of vaccine delivery.

“Addressing vaccine hesitancy adequately is one of the biggest challenges we face, especially for the HPV vaccine,” Dr. Bruni said. “As the WHO document states, understanding social, cultural, societal, and other barriers affecting acceptance and uptake of the vaccine will be critical for overcoming vaccine hesitancy and countering misinformation.”

This research was funded by a grant from Instituto de Salud Carlos III and various other grants. Dr. Bruni and coauthors said they have no relevant disclosures.

Many countries have “a long way to go” toward meeting the World Health Organization’s target for human papilloma virus (HPV) vaccination, according to researchers.

The WHO’s goal is to have HPV vaccines delivered to 90% of all adolescent girls by 2030, part of the organization’s larger goal to “eliminate” cervical cancer, or reduce the annual incidence of cervical cancer to below 4 cases per 100,000 people globally.

Laia Bruni, MD, PhD, of Catalan Institute of Oncology in Barcelona, and colleagues outlined the progress made thus far toward reaching the WHO’s goals in an article published in Preventive Medicine.

The authors noted that cervical cancer caused by HPV is a “major public health problem, especially in low- and middle-income countries (LMIC).”

However, vaccines against HPV have been available since 2006 and have been recommended by the WHO since 2009.

HPV vaccines have been introduced into many national immunization schedules. Among the 194 WHO member states, 107 (55%) had introduced HPV vaccination as of June 2020, according to estimates from the WHO and the United Nations International Children’s Emergency Fund (UNICEF).

Still, vaccine introduction and coverages are suboptimal, according to several studies and international agencies.

In their article, Dr. Bruni and colleagues describe the mid-2020 status of HPV vaccine introduction, based on WHO/UNICEF estimates of national HPV immunization coverage from 2010 to 2019.
 

HPV vaccination by region

The Americas and Europe are by far the WHO regions with the highest rates of HPV vaccination, with 85% and 77% of their countries, respectively, having already introduced HPV vaccination, either partially or nationwide.

In 2019, a record number of introductions, 16, were reported, mostly in LMICs where access has been limited. In prior years, the average had been a relatively steady 7-8 introductions per year.

The percentage of high-income countries (HICs) that have introduced HPV vaccination exceeds 80%. LMICs started introducing HPV vaccination later and at a slower pace, compared with HICs. By the end of 2019, only 41% of LMICs had introduced vaccination. However, of the new introductions in 2019, 87% were in LMICs.

In 2019, the average performance coverage for HPV vaccination programs in 99 countries (both HICs and LMICs) was around 67% for the first vaccine dose and 53% for the final dose.

Median performance coverage was higher in LMICs than in HICs for the first dose (80% and 72%, respectively), but mean dropout rates were higher in LMICs than in HICs (18% and 11%, respectively).

Coverage of more than 90% was achieved for the last dose in only five countries (6%). Twenty-two countries (21%) achieved coverages of 75% or higher, while 35 countries (40%) had final dose coverages of 50% or less.

Global coverage of the final HPV vaccine dose (weighted by population size) was estimated at 15%. According to the authors, that low percentage can be explained by the fact that many of the most populous countries have either not yet introduced HPV vaccination or have low performance.

The countries with highest cervical cancer burden have had limited secondary prevention and have been less likely to provide access to vaccination, the authors noted. However, this trend appears to be reversing, with 14 new LMICs providing HPV vaccination in 2019.
 

HPV vaccination by sex

By 2019, almost a third of the 107 HPV vaccination programs (n = 33) were “gender neutral,” with girls and boys receiving HPV vaccines. Generally, LMICs targeted younger girls (9-10 years) compared with HICs (11-13 years).

Dr. Bruni and colleagues estimated that 15% of girls and 4% of boys were vaccinated globally with the full course of vaccine. At least one dose was received by 20% of girls and 5% of boys.

From 2010 to 2019, HPV vaccination rates in HICs rose from 42% in girls and 0% in boys to 88% and 44%, respectively. In LMICs, over the same period, rates rose from 4% in girls and 0% in boys to 40% and 5%, respectively.
 

Obstacles and the path forward

The COVID-19 pandemic has halted HPV vaccine delivery in the majority of countries, Dr. Bruni and colleagues noted. About 70 countries had reported program interruptions by August 2020, and delays to HPV vaccine introductions were anticipated for other countries.

An economic downturn could have further far-reaching effects on plans to introduce HPV vaccines, Dr. Bruni and colleagues observed.

While meeting the 2030 target will be challenging, the authors noted that, in every geographic area, some programs are meeting the 90% target.

“HPV national programs should aim to get 90+% of girls vaccinated before the age of 15,” Dr. Bruni said in an interview. “This is a feasible goal, and some countries have succeeded, such as Norway and Rwanda. Average performance, however, is around 55%, and that shows that it is not an easy task.”

Dr. Bruni underscored the four main actions that should be taken to achieve 90% coverage of HPV vaccination, as outlined in the WHO cervical cancer elimination strategy:

• Secure sufficient and affordable HPV vaccines.
• Increase the quality and coverage of vaccination.
• Improve communication and social mobilization.
• Innovate to improve efficiency of vaccine delivery.

“Addressing vaccine hesitancy adequately is one of the biggest challenges we face, especially for the HPV vaccine,” Dr. Bruni said. “As the WHO document states, understanding social, cultural, societal, and other barriers affecting acceptance and uptake of the vaccine will be critical for overcoming vaccine hesitancy and countering misinformation.”

This research was funded by a grant from Instituto de Salud Carlos III and various other grants. Dr. Bruni and coauthors said they have no relevant disclosures.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

Single-nucleotide polymorphism (SNP) chips often fail to correctly identify rare variants, a large study suggests.

In fact, SNP chips are “extremely unreliable for genotyping very rare pathogenic variants,” and a positive result for such a variant “is more likely to be wrong than right,” researchers reported in the BMJ.

The authors explained that SNP chips are “DNA microarrays that test genetic variation at many hundreds of thousands of specific locations across the genome.” Although SNP chips have proven accurate in identifying common variants, past reports have suggested that SNP chips perform poorly for genotyping rare variants.

To gain more insight, Caroline Wright, PhD, of the University of Exeter (England) and colleagues conducted a large study.

The researchers analyzed data on 49,908 people from the UK Biobank who had SNP chip and next-generation sequencing results, as well as an additional 21 people who purchased consumer genetic tests and shared their data online via the Personal Genome Project.

The researchers compared the SNP chip and sequencing results. They also selected rare pathogenic variants in BRCA1 and BRCA2 for detailed analysis of clinically actionable variants in the UK Biobank, and they assessed BRCA-related cancers in participants using cancer registry data.
 

Largest evaluation of SNP chips

SNP chips performed well for common variants, the researchers found. Sensitivity, specificity, positive-predictive value, and negative-predictive value all exceeded 99% for 108,574 common variants.

For rare variants, SNP chips performed poorly, with a positive-predictive value of 16% for variants with a frequency below 0.001% in the UK Biobank.

“The study provides the largest evaluation of the performance of SNP chips for genotyping genetic variants at different frequencies in the population, particularly focusing on very rare variants,” Dr. Wright said. “The biggest surprise was how poorly the SNP chips we evaluated performed for rare variants.”

Dr. Wright noted that there is an inherent problem built into using SNP chip technology to genotype very rare variants.

“The SNP chip technology relies on clustering data from multiple individuals in order to determine what genotype each individual has at a specific position in their genome,” Dr. Wright explained. “Although this method works very well for common variants, the rarer the variant, the harder it is to distinguish from experimental noise.”
 

False positives and cancer: ‘Don’t trust the results’

The researchers found that, for rare BRCA variants (frequency below 0.01%), SNP chips had a sensitivity of 34.6%, specificity of 98.3%, negative-predictive value of 99.9%, and positive-predictive value of 4.2%.

Rates of BRCA-related cancers in patients with positive SNP chip results were similar to rates in age-matched control subjects because “the vast majority of variants were false positives,” the researchers noted.

“If these variants are incorrectly genotyped – that is, false positives detected – a woman could be offered screening or even prophylactic surgery inappropriately when she is more likely to be at population background risk [for BRCA-related cancers],” Dr. Wright said.

“For very-rare-disease–causing genetic variants, don’t trust the results from SNP chips; for example, those from direct-to-consumer genetic tests. Never use them to guide clinical action without diagnostic validation,” she added.

Heather Hampel, a genetic counselor and researcher at the Ohio State University Comprehensive Cancer Center in Columbus, agreed.

“Positive results on SNP-based tests need to be confirmed by medical-grade genetic testing using a sequencing technology,” she said. “Negative results on an SNP- based test cannot be considered to rule out mutations in BRCA1/2 or other cancer-susceptibility genes, so individuals with strong personal and family histories of cancer should be seen by a genetic counselor to consider medical-grade genetic testing using a sequencing technology.”

Practicing oncologists can trust patients’ prior germline genetic test results if the testing was performed in a cancer genetics clinic, which uses sequencing-based technologies, Ms. Hampel noted.

“If the test was performed before 2013, there are likely new genes that have been discovered for which their patient was not tested, and repeat testing may be warranted,” Ms. Hampel said. “A referral to a cancer genetic counselor would be appropriate.”

Ms. Hampel disclosed relationships with Genome Medical, GI OnDemand, Invitae Genetics, and Promega. Dr. Wright and her coauthors disclosed no conflicts of interest. The group’s research was conducted using the UK Biobank and the University of Exeter High-Performance Computing, with funding from the Wellcome Trust and the National Institute for Health Research.

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at [email protected].

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at [email protected].

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at [email protected].

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

It’s time for a large-scale phase 2 study into whether supplementary estrogen can relieve multiple sclerosis (MS) symptoms in menopausal women with the disease, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.

“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”

Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.

Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”

Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”

Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”

In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.

“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”

What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.

Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”

She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”

Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

A version of this article first appeared on WebMD.com .