The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

The infants of obese pregnant women had a 55% higher adjusted perinatal death rate, compared with those of normal-weight pregnant women, but lower gestational age had a mediating effect, based on data from nearly 400,000 women-infant pairs.

“While some obesity-related causes of fetal death are known, the exact pathophysiology behind the effects of obesity on perinatal death are not completely understood,” Jeffrey N. Bone, MD, of the University of British Columbia, Vancouver, and colleagues wrote. Higher body mass index prior to pregnancy also is associated with preterm delivery, but the effect of gestational age on the association between BMI and infant mortality has not been well explored.

In a study published in PLOS ONE, the researchers reviewed data from nearly 400,000 women obtained through the British Columbia Perinatal Database Registry, which collects obstetric and neonatal data from hospital charts and from delivery records of home births. Births at less than 20 weeks’ gestation and late pregnancy terminations were excluded.

BMI was based on self-reported prepregnancy height and weight; of the 392,820 included women, 12.8% were classified as obese, 20.6% were overweight, 60.6% were normal weight, and 6.0% were underweight. Infants of women with higher BMI had a lower gestational age at delivery. Perinatal mortality occurred in 1,834 pregnancies (0.5%). In adjusted analysis, infant perinatal death was significantly more likely for obese women (adjusted odds ratio, 1.55) and overweight women (aOR, 1.22).

However, 63.1% of this association in obese women was mediated by gestational age of the infant at delivery, with aORs of 1.32 and 1.18 for natural indirect and natural direct effects, respectively, compared with that of normal-weight women. Similar, but lesser effects were noted for overweight women, with aORs of 1.11 and 1.10, respectively. “Direct effects were higher, and mediation was lower for stillbirth than for neonatal death, where the total effect was entirely indirect,” but the confidence intervals remained consistent with the primary analyses, the researchers noted.

The increased perinatal death rates of infants of obese and overweight women reflect data from previous studies, but the current study’s use of mediation analysis offers new insight on the mechanism by which perinatal death rates increase with higher maternal BMI, the researchers wrote.

The study findings were limited by several factors including the need to consider potential common risk factors for both perinatal death and early delivery that would be affected by maternal obesity, the researchers noted. Other limitations included the use of gestational age at stillbirth, which represents an approximation of fetal death in some cases, and the use of self-reports for prepregnancy maternal BMI.

However, the results were strengthened by the large, population-based design and information on potential confounding variables, and suggest that early gestational age at delivery may play a role in maternal obesity-related perinatal death risk.

“To better inform the pregnancy management in obese women, further studies should continue to disentangle the causal pathways under which obesity increases the risk of perinatal death, including, for example, gestational diabetes and other obesity-related pregnancy complications,” they concluded.
 

More testing and counseling are needed

The current study is important because obesity rates continue to increase in the reproductive-age population, Marissa Platner, MD, of Emory University, Atlanta, said in an interview. “Obesity has become a known risk factor for adverse pregnancy outcomes, specifically the risk of stillbirth and perinatal death. However, the authors correctly point out that the underlying cause of these perinatal deaths in women with obesity is unclear. Additionally, ACOG recently updated their clinical guidelines to recommend routine antenatal testing for women with obesity due to these increased rates of stillbirth.

“I was not surprised by these findings; similar to previous literature, the risks of perinatal death seem to have a dose-response relationship with increasing BMI. We know that women with prepregnancy obesity are also at higher risk of perinatal complications in the preterm period, which would increase the risk of perinatal death,” Dr. Platner said

“I think the take-home message for clinicians is twofold,” Dr. Platner said. First, “we need to take the updated antenatal testing guidelines from ACOG very seriously and implement these in our practices.” Second, “in the preconception or early antepartum period, these patients should be thoroughly counseled on the associated risks of pregnancy and discuss appropriate gestational weight gain guidelines and lifestyle modifications.”

However, “additional research is needed in a U.S. population with higher rates of obesity to determine the true effects of obesity on perinatal deaths and to further elucidate the underlying pathophysiology and disease processes that may lead to increased risk of both stillbirth and perinatal deaths,” Dr. Platner emphasized.

*This story was updated on March 23, 2022.

The study was supported by the Sick Kids Foundation and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination (Achiron et al). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies (Hauser et al).

Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

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

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

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

Cancer care is not a top priority for the United Nations agency that is helping Ukrainian refugees across the border into neighboring countries, which makes the role of oncology groups vitally important.

“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.

“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”

Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.

He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.

With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.

“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”

So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.

“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”

“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.

Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.

Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”

Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.

Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”

Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”

The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.

“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.

In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.

“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”

Separately, there is also an ASCO resource page, as well as an ECO resource page.

The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.

Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”

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

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

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

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

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

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.

It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.

The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.

Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”

Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.

The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
 

COVID-19 brought the issue to a head

Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.

The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”

The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.

The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.

Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.

Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.

Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.

Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.

There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

A sudden drop in blood pressure when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic BP response to standing greater than 6.5 mm Hg had almost double the risk of major adverse cardiovascular events (MACE) during follow-up, compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP (hazard ratio, 1.94; 95% confidence interval, 1.10 to 3.44), the study showed.

“The clinical implication is important, because now doctors measure blood pressure in young people in the upright posture, but what we say is it must be measured also while standing,” said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality, particularly in older patients, but few prognostic data exist in those who are young to middle age, he noted.

The study, published in Hypertension, included 1,207 participants ages 18-45 years with untreated stage 1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-100 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The average age at enrollment was 33 years.

BP was measured at two visits 2 weeks apart, with each visit including three supine measurements taken after the patient had lain down for a minimum of 5 minutes, followed by three standing measurements taken 1 minute apart.

Based on the average of standing-lying BP differences during the two visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) systolic BP response to standing.

The 120 participants classified as “hyper-reactors” averaged an 11.4 mm Hg systolic BP increase upon standing, whereas the rest of the participants averaged a 3.8 mm Hg fall in systolic BP upon standing.

At their initial visit, hyper-reactors were more likely to be smokers (32.1% vs. 19.9%) and coffee drinkers (81.7% vs. 73%) and to have ambulatory hypertension (90.8% vs. 76.4%).

They were, however, no more likely to have a family history of cardiovascular events and had a lower supine systolic BP (140.5 mm Hg vs. 146.0 mm Hg), lower total cholesterol (4.93 mmol/L vs. 5.13 mmol/L), and higher HDL cholesterol (1.42 mmol/L vs. 1.35 mmol/L).

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal systolic BP response were more likely to be treated for hypertension during follow-up (81.7% vs. 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyper-reactors than normal responders (118.4 nmol/mol vs. 77.0 nmol/mol; P = .005).

During a median follow-up of 17.3 years, there were 105 major cardiovascular events, broadly defined to include acute coronary syndromes (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (20).

The near doubling of MACE risk among hyper-reactors remained when atrial fibrillation was excluded and when 24-hour ambulatory systolic BP was included in the model, the author reported.

The results are in line with previous studies, indicating that hyper-reactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Dr. Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults, whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person’s BP spikes upon standing, “then you have to treat them according to the average of the lying and the standing pressure,” Dr. Palatini said. “In these people, blood pressure should be treated earlier than in the past.”

“The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice,” Nieca Goldberg, MD, medical director of the Atria Institute, New York, and an associate professor of medicine at New York University Grossman School of Medicine, commented via email.

She noted that standing blood pressures are usually not taken as part of a medical visit and, in fact, seated blood pressures are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

“By incorporating standing BP, we will improve our diagnosis for hypertension, and with interventions such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease,” said Dr. Goldberg, who is also a spokesperson for the American Heart Association.

“The biggest barrier is that office visits are limited to 15 minutes, and not enough time is spent on the vital signs,” she noted. “We need changes to the health care system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options.”

Limitations of the present study are that 72.7% of participants were men and all were White, Dr. Palatini said. Future work is also needed to create a uniform definition of BP hyper-reactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Dr. Goldberg reported being a spokesperson for the American Heart Association.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Pfizer is voluntarily recalling some antihypertensive medications because of unacceptable levels of a potential carcinogen, the company announced. 

The affected products are quinapril HCI/hydrochlorothiazide (Accuretic) tablets that Pfizer distributes, and two authorized generics, quinapril plus hydrochlorothiazide and quinapril HCI/hydrochlorothiazide, distributed by Greenstone. The drugs have been withdrawn because of the presence of nitrosamine, N-nitroso-quinapril.

“Although long-term ingestion of N-nitroso-quinapril may be associated with a potential increased cancer risk in humans, there is no immediate risk to patients taking this medication,” Pfizer said in a news release.

The tablets are indicated for the treatment of hypertension. Patients currently taking the products are asked to consult with their doctor about alternative treatment options.

To date, there have been no reports of adverse events related to the recall, the company said.

In all, Pfizer is recalling six lots of Accuretic tablets (two at 10 mg/12.5 mg, three at 20 mg/12.5 mg, and one at 20 mg/25 mg), one lot of quinapril plus hydrochlorothiazide 20-mg/25-mg tablets, and four lots of quinapril HCl/ hydrochlorothiazide tablets (three at 20 mg/12.5 mg and one at 20 mg/25 mg)

The recalled tablets were sold in 90-count bottles distributed in the United States and Puerto Rico between November 2019 and March 2022. Product codes and lot numbers of the recalled medications are listed on the Pfizer website.

Patients who are taking this product should consult with their health care provider or pharmacy to determine if they have the affected product. Those with the affected tablets should contact claims management firm Sedgwick by phone at 888-843-0247 Monday through Friday from 8 a.m. to 5 p.m. ET for instructions on how to return their product and obtain reimbursement.

Health care providers with medical questions regarding the recall can contact Pfizer by telephone at 800-438-1985, option 3, Monday through Friday 8 a.m. to 9 p.m. ET.

Providers should report adverse reactions or quality problems they experience using these tablets to Pfizer either by telephone at 800-438-1985, option 1, by regular mail or by fax, or to the Food and Drug Administration’s MedWatch program.

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

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Complete gross resection is much less likely for advanced ovarian cancer in women with mesenchymal tumors and complex preoperative CT findings, according to a report at the Society of Gynecologic Oncology annual meeting.

Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.

The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.

He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”

For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.

Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.

What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.

The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.

The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.

Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.

Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”

Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).

Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.

“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.

No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.

Four years ago, inside the most prestigious hospital in Tennessee, nurse RaDonda Vaught withdrew a vial from an electronic medication cabinet, administered the drug to a patient, and somehow overlooked signs of a terrible and deadly mistake.

The patient was supposed to get Versed, a sedative intended to calm her before being scanned in a large, MRI-like machine. But Ms. Vaught accidentally grabbed vecuronium, a powerful paralyzer, which stopped the patient’s breathing and left her brain-dead before the error was discovered.

Ms. Vaught, 38, admitted her mistake at a Tennessee Board of Nursing hearing last year, saying she became “complacent” in her job and “distracted” by a trainee while operating the computerized medication cabinet. She did not shirk responsibility for the error, but she said the blame was not hers alone.

“I know the reason this patient is no longer here is because of me,” Ms. Vaught said, starting to cry. “There won’t ever be a day that goes by that I don’t think about what I did.”

If Ms. Vaught’s story followed the path of most medical errors, it would have been over hours later, when the Board of Nursing revoked her RN license and almost certainly ended her nursing career. But Ms. Vaught’s case is different: This week she goes on trial in Nashville on criminal charges of reckless homicide and felony abuse of an impaired adult for the killing of Charlene Murphey, a 75-year-old patient who died at Vanderbilt University Medical Center on Dec. 27, 2017.

Prosecutors do not allege in their court filings that Ms. Vaught intended to hurt Ms. Murphey or was impaired by any substance when she made the mistake, so her prosecution is a rare example of a health care worker facing years in prison for a medical error. Fatal errors are generally handled by licensing boards and civil courts. And experts say prosecutions like Ms. Vaught’s loom large for a profession terrified of the criminalization of such mistakes — especially because her case hinges on an automated system for dispensing drugs that many nurses use every day.

The Nashville district attorney’s office declined to discuss Ms. Vaught’s trial. Ms. Vaught’s lawyer, Peter Strianse, did not respond to requests for comment. Vanderbilt University Medical Center has repeatedly declined to comment on Ms. Vaught’s trial or its procedures.

Ms. Vaught’s trial will be followed by nurses nationwide, many of whom worry a conviction may set a precedent even as the coronavirus pandemic leaves countless nurses exhausted, demoralized, and likely more prone to error.

Janie Harvey Garner, a St. Louis registered nurse and founder of Show Me Your Stethoscope, a nursing group with more than 600,000 members on Facebook, said the group has closely watched Ms. Vaught’s case for years out of concern for her fate — and their own.

Ms. Garner said most nurses know all too well the pressures that contribute to such an error: long hours, crowded hospitals, imperfect protocols, and the inevitable creep of complacency in a job with daily life-or-death stakes.

Ms. Garner said she once switched powerful medications just as Ms. Vaught did and caught her mistake only in a last-minute triple-check.

“In response to a story like this one, there are two kinds of nurses,” Ms. Garner said. “You have the nurses who assume they would never make a mistake like that, and usually it’s because they don’t realize they could. And the second kind are the ones who know this could happen, any day, no matter how careful they are. This could be me. I could be RaDonda.”

As the trial begins, the Nashville DA’s prosecutors will argue that Ms. Vaught’s error was anything but a common mistake any nurse could make. Prosecutors will say she ignored a cascade of warnings that led to the deadly error.

The case hinges on the nurse’s use of an electronic medication cabinet, a computerized device that dispenses a range of drugs. According to documents filed in the case, Ms. Vaught initially tried to withdraw Versed from a cabinet by typing “VE” into its search function without realizing she should have been looking for its generic name, midazolam. When the cabinet did not produce Versed, Ms. Vaught triggered an “override” that unlocked a much larger swath of medications, then searched for “VE” again. This time, the cabinet offered vecuronium.

Ms. Vaught then overlooked or bypassed at least five warnings or pop-ups saying she was withdrawing a paralyzing medication, documents state. She also did not recognize that Versed is a liquid but vecuronium is a powder that must be mixed into liquid, documents state.

Finally, just before injecting the vecuronium, Ms. Vaught stuck a syringe into the vial, which would have required her to “look directly” at a bottle cap that read “Warning: Paralyzing Agent,” the DA’s documents state.

The DA’s office points to this override as central to Ms. Vaught’s reckless homicide charge. Ms. Vaught acknowledges she performed an override on the cabinet. But she and others say overrides are a normal operating procedure used daily at hospitals.

While testifying before the nursing board last year, foreshadowing her defense in the upcoming trial, Ms. Vaught said at the time of Ms. Murphey’s death that Vanderbilt was instructing nurses to use overrides to overcome cabinet delays and constant technical problems caused by an ongoing overhaul of the hospital’s electronic health records system.

Ms. Murphey’s care alone required at least 20 cabinet overrides in just three days, Ms. Vaught said.

“Overriding was something we did as part of our practice every day,” Ms. Vaught said. “You couldn’t get a bag of fluids for a patient without using an override function.”

Overrides are common outside of Vanderbilt too, according to experts following Ms. Vaught’s case.

Michael Cohen, president emeritus of the Institute for Safe Medication Practices, and Lorie Brown, past president of the American Association of Nurse Attorneys, each said it is common for nurses to use an override to obtain medication in a hospital.

Mr. Cohen and Ms. Brown stressed that even with an override it should not have been so easy to access vecuronium.

“This is a medication that you should never, ever, be able to override to,” Ms. Brown said. “It’s probably the most dangerous medication out there.”

Mr. Cohen said that in response to Ms. Vaught’s case, manufacturers of medication cabinets modified the devices’ software to require up to five letters to be typed when searching for drugs during an override, but not all hospitals have implemented this safeguard. Two years after Ms. Vaught’s error, Mr. Cohen’s organization documented a “strikingly similar” incident in which another nurse swapped Versed with another drug, verapamil, while using an override and searching with just the first few letters. That incident did not result in a patient’s death or criminal prosecution, Mr. Cohen said.

Maureen Shawn Kennedy, the editor-in-chief emerita of the American Journal of Nursing, wrote in 2019 that Ms. Vaught’s case was “every nurse’s nightmare.”

In the pandemic, she said, this is truer than ever.

“We know that the more patients a nurse has, the more room there is for errors,” Ms. Kennedy said. “We know that when nurses work longer shifts, there is more room for errors. So I think nurses get very concerned because they know this could be them.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Four years ago, inside the most prestigious hospital in Tennessee, nurse RaDonda Vaught withdrew a vial from an electronic medication cabinet, administered the drug to a patient, and somehow overlooked signs of a terrible and deadly mistake.

The patient was supposed to get Versed, a sedative intended to calm her before being scanned in a large, MRI-like machine. But Ms. Vaught accidentally grabbed vecuronium, a powerful paralyzer, which stopped the patient’s breathing and left her brain-dead before the error was discovered.

Ms. Vaught, 38, admitted her mistake at a Tennessee Board of Nursing hearing last year, saying she became “complacent” in her job and “distracted” by a trainee while operating the computerized medication cabinet. She did not shirk responsibility for the error, but she said the blame was not hers alone.

“I know the reason this patient is no longer here is because of me,” Ms. Vaught said, starting to cry. “There won’t ever be a day that goes by that I don’t think about what I did.”

If Ms. Vaught’s story followed the path of most medical errors, it would have been over hours later, when the Board of Nursing revoked her RN license and almost certainly ended her nursing career. But Ms. Vaught’s case is different: This week she goes on trial in Nashville on criminal charges of reckless homicide and felony abuse of an impaired adult for the killing of Charlene Murphey, a 75-year-old patient who died at Vanderbilt University Medical Center on Dec. 27, 2017.

Prosecutors do not allege in their court filings that Ms. Vaught intended to hurt Ms. Murphey or was impaired by any substance when she made the mistake, so her prosecution is a rare example of a health care worker facing years in prison for a medical error. Fatal errors are generally handled by licensing boards and civil courts. And experts say prosecutions like Ms. Vaught’s loom large for a profession terrified of the criminalization of such mistakes — especially because her case hinges on an automated system for dispensing drugs that many nurses use every day.

The Nashville district attorney’s office declined to discuss Ms. Vaught’s trial. Ms. Vaught’s lawyer, Peter Strianse, did not respond to requests for comment. Vanderbilt University Medical Center has repeatedly declined to comment on Ms. Vaught’s trial or its procedures.

Ms. Vaught’s trial will be followed by nurses nationwide, many of whom worry a conviction may set a precedent even as the coronavirus pandemic leaves countless nurses exhausted, demoralized, and likely more prone to error.

Janie Harvey Garner, a St. Louis registered nurse and founder of Show Me Your Stethoscope, a nursing group with more than 600,000 members on Facebook, said the group has closely watched Ms. Vaught’s case for years out of concern for her fate — and their own.

Ms. Garner said most nurses know all too well the pressures that contribute to such an error: long hours, crowded hospitals, imperfect protocols, and the inevitable creep of complacency in a job with daily life-or-death stakes.

Ms. Garner said she once switched powerful medications just as Ms. Vaught did and caught her mistake only in a last-minute triple-check.

“In response to a story like this one, there are two kinds of nurses,” Ms. Garner said. “You have the nurses who assume they would never make a mistake like that, and usually it’s because they don’t realize they could. And the second kind are the ones who know this could happen, any day, no matter how careful they are. This could be me. I could be RaDonda.”

As the trial begins, the Nashville DA’s prosecutors will argue that Ms. Vaught’s error was anything but a common mistake any nurse could make. Prosecutors will say she ignored a cascade of warnings that led to the deadly error.

The case hinges on the nurse’s use of an electronic medication cabinet, a computerized device that dispenses a range of drugs. According to documents filed in the case, Ms. Vaught initially tried to withdraw Versed from a cabinet by typing “VE” into its search function without realizing she should have been looking for its generic name, midazolam. When the cabinet did not produce Versed, Ms. Vaught triggered an “override” that unlocked a much larger swath of medications, then searched for “VE” again. This time, the cabinet offered vecuronium.

Ms. Vaught then overlooked or bypassed at least five warnings or pop-ups saying she was withdrawing a paralyzing medication, documents state. She also did not recognize that Versed is a liquid but vecuronium is a powder that must be mixed into liquid, documents state.

Finally, just before injecting the vecuronium, Ms. Vaught stuck a syringe into the vial, which would have required her to “look directly” at a bottle cap that read “Warning: Paralyzing Agent,” the DA’s documents state.

The DA’s office points to this override as central to Ms. Vaught’s reckless homicide charge. Ms. Vaught acknowledges she performed an override on the cabinet. But she and others say overrides are a normal operating procedure used daily at hospitals.

While testifying before the nursing board last year, foreshadowing her defense in the upcoming trial, Ms. Vaught said at the time of Ms. Murphey’s death that Vanderbilt was instructing nurses to use overrides to overcome cabinet delays and constant technical problems caused by an ongoing overhaul of the hospital’s electronic health records system.

Ms. Murphey’s care alone required at least 20 cabinet overrides in just three days, Ms. Vaught said.

“Overriding was something we did as part of our practice every day,” Ms. Vaught said. “You couldn’t get a bag of fluids for a patient without using an override function.”

Overrides are common outside of Vanderbilt too, according to experts following Ms. Vaught’s case.

Michael Cohen, president emeritus of the Institute for Safe Medication Practices, and Lorie Brown, past president of the American Association of Nurse Attorneys, each said it is common for nurses to use an override to obtain medication in a hospital.

Mr. Cohen and Ms. Brown stressed that even with an override it should not have been so easy to access vecuronium.

“This is a medication that you should never, ever, be able to override to,” Ms. Brown said. “It’s probably the most dangerous medication out there.”

Mr. Cohen said that in response to Ms. Vaught’s case, manufacturers of medication cabinets modified the devices’ software to require up to five letters to be typed when searching for drugs during an override, but not all hospitals have implemented this safeguard. Two years after Ms. Vaught’s error, Mr. Cohen’s organization documented a “strikingly similar” incident in which another nurse swapped Versed with another drug, verapamil, while using an override and searching with just the first few letters. That incident did not result in a patient’s death or criminal prosecution, Mr. Cohen said.

Maureen Shawn Kennedy, the editor-in-chief emerita of the American Journal of Nursing, wrote in 2019 that Ms. Vaught’s case was “every nurse’s nightmare.”

In the pandemic, she said, this is truer than ever.

“We know that the more patients a nurse has, the more room there is for errors,” Ms. Kennedy said. “We know that when nurses work longer shifts, there is more room for errors. So I think nurses get very concerned because they know this could be them.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Four years ago, inside the most prestigious hospital in Tennessee, nurse RaDonda Vaught withdrew a vial from an electronic medication cabinet, administered the drug to a patient, and somehow overlooked signs of a terrible and deadly mistake.

The patient was supposed to get Versed, a sedative intended to calm her before being scanned in a large, MRI-like machine. But Ms. Vaught accidentally grabbed vecuronium, a powerful paralyzer, which stopped the patient’s breathing and left her brain-dead before the error was discovered.

Ms. Vaught, 38, admitted her mistake at a Tennessee Board of Nursing hearing last year, saying she became “complacent” in her job and “distracted” by a trainee while operating the computerized medication cabinet. She did not shirk responsibility for the error, but she said the blame was not hers alone.

“I know the reason this patient is no longer here is because of me,” Ms. Vaught said, starting to cry. “There won’t ever be a day that goes by that I don’t think about what I did.”

If Ms. Vaught’s story followed the path of most medical errors, it would have been over hours later, when the Board of Nursing revoked her RN license and almost certainly ended her nursing career. But Ms. Vaught’s case is different: This week she goes on trial in Nashville on criminal charges of reckless homicide and felony abuse of an impaired adult for the killing of Charlene Murphey, a 75-year-old patient who died at Vanderbilt University Medical Center on Dec. 27, 2017.

Prosecutors do not allege in their court filings that Ms. Vaught intended to hurt Ms. Murphey or was impaired by any substance when she made the mistake, so her prosecution is a rare example of a health care worker facing years in prison for a medical error. Fatal errors are generally handled by licensing boards and civil courts. And experts say prosecutions like Ms. Vaught’s loom large for a profession terrified of the criminalization of such mistakes — especially because her case hinges on an automated system for dispensing drugs that many nurses use every day.

The Nashville district attorney’s office declined to discuss Ms. Vaught’s trial. Ms. Vaught’s lawyer, Peter Strianse, did not respond to requests for comment. Vanderbilt University Medical Center has repeatedly declined to comment on Ms. Vaught’s trial or its procedures.

Ms. Vaught’s trial will be followed by nurses nationwide, many of whom worry a conviction may set a precedent even as the coronavirus pandemic leaves countless nurses exhausted, demoralized, and likely more prone to error.

Janie Harvey Garner, a St. Louis registered nurse and founder of Show Me Your Stethoscope, a nursing group with more than 600,000 members on Facebook, said the group has closely watched Ms. Vaught’s case for years out of concern for her fate — and their own.

Ms. Garner said most nurses know all too well the pressures that contribute to such an error: long hours, crowded hospitals, imperfect protocols, and the inevitable creep of complacency in a job with daily life-or-death stakes.

Ms. Garner said she once switched powerful medications just as Ms. Vaught did and caught her mistake only in a last-minute triple-check.

“In response to a story like this one, there are two kinds of nurses,” Ms. Garner said. “You have the nurses who assume they would never make a mistake like that, and usually it’s because they don’t realize they could. And the second kind are the ones who know this could happen, any day, no matter how careful they are. This could be me. I could be RaDonda.”

As the trial begins, the Nashville DA’s prosecutors will argue that Ms. Vaught’s error was anything but a common mistake any nurse could make. Prosecutors will say she ignored a cascade of warnings that led to the deadly error.

The case hinges on the nurse’s use of an electronic medication cabinet, a computerized device that dispenses a range of drugs. According to documents filed in the case, Ms. Vaught initially tried to withdraw Versed from a cabinet by typing “VE” into its search function without realizing she should have been looking for its generic name, midazolam. When the cabinet did not produce Versed, Ms. Vaught triggered an “override” that unlocked a much larger swath of medications, then searched for “VE” again. This time, the cabinet offered vecuronium.

Ms. Vaught then overlooked or bypassed at least five warnings or pop-ups saying she was withdrawing a paralyzing medication, documents state. She also did not recognize that Versed is a liquid but vecuronium is a powder that must be mixed into liquid, documents state.

Finally, just before injecting the vecuronium, Ms. Vaught stuck a syringe into the vial, which would have required her to “look directly” at a bottle cap that read “Warning: Paralyzing Agent,” the DA’s documents state.

The DA’s office points to this override as central to Ms. Vaught’s reckless homicide charge. Ms. Vaught acknowledges she performed an override on the cabinet. But she and others say overrides are a normal operating procedure used daily at hospitals.

While testifying before the nursing board last year, foreshadowing her defense in the upcoming trial, Ms. Vaught said at the time of Ms. Murphey’s death that Vanderbilt was instructing nurses to use overrides to overcome cabinet delays and constant technical problems caused by an ongoing overhaul of the hospital’s electronic health records system.

Ms. Murphey’s care alone required at least 20 cabinet overrides in just three days, Ms. Vaught said.

“Overriding was something we did as part of our practice every day,” Ms. Vaught said. “You couldn’t get a bag of fluids for a patient without using an override function.”

Overrides are common outside of Vanderbilt too, according to experts following Ms. Vaught’s case.

Michael Cohen, president emeritus of the Institute for Safe Medication Practices, and Lorie Brown, past president of the American Association of Nurse Attorneys, each said it is common for nurses to use an override to obtain medication in a hospital.

Mr. Cohen and Ms. Brown stressed that even with an override it should not have been so easy to access vecuronium.

“This is a medication that you should never, ever, be able to override to,” Ms. Brown said. “It’s probably the most dangerous medication out there.”

Mr. Cohen said that in response to Ms. Vaught’s case, manufacturers of medication cabinets modified the devices’ software to require up to five letters to be typed when searching for drugs during an override, but not all hospitals have implemented this safeguard. Two years after Ms. Vaught’s error, Mr. Cohen’s organization documented a “strikingly similar” incident in which another nurse swapped Versed with another drug, verapamil, while using an override and searching with just the first few letters. That incident did not result in a patient’s death or criminal prosecution, Mr. Cohen said.

Maureen Shawn Kennedy, the editor-in-chief emerita of the American Journal of Nursing, wrote in 2019 that Ms. Vaught’s case was “every nurse’s nightmare.”

In the pandemic, she said, this is truer than ever.

“We know that the more patients a nurse has, the more room there is for errors,” Ms. Kennedy said. “We know that when nurses work longer shifts, there is more room for errors. So I think nurses get very concerned because they know this could be them.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.