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Don’t discontinue osteoporosis meds for COVID-19 vaccines, expert guidance says
COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.
They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.
The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.
There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”
There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.
There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.
A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.
No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.
The guidance includes some recommendations for specific osteoporosis medications.
- Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
- Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
- Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
- Teriparatide and abaloparatide should be continued.
- Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
- Raloxifene should be continued in patients receiving COVID-19 vaccination.
Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
Dr. Jan De Beur has no relevant financial disclosures.
COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.
They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.
The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.
There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”
There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.
There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.
A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.
No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.
The guidance includes some recommendations for specific osteoporosis medications.
- Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
- Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
- Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
- Teriparatide and abaloparatide should be continued.
- Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
- Raloxifene should be continued in patients receiving COVID-19 vaccination.
Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
Dr. Jan De Beur has no relevant financial disclosures.
COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.
They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.
The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.
There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”
There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.
There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.
A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.
No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.
The guidance includes some recommendations for specific osteoporosis medications.
- Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
- Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
- Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
- Teriparatide and abaloparatide should be continued.
- Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
- Raloxifene should be continued in patients receiving COVID-19 vaccination.
Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
Dr. Jan De Beur has no relevant financial disclosures.
Inpatient sodium imbalances linked to adverse COVID-19 outcomes
Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.
In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.
Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.
“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.
The findings will be presented at the upcoming news conference held by the Endocrine Society
Should sodium be included in a risk calculator for COVID-19?
Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”
Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”
Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.
“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.
“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.
He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”
Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”
Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
Hyper- and hyponatremia linked to adverse COVID-19 outcomes
In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.
The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).
In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.
Overall, hyponatremia was not associated with death (P = .41).
During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.
In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).
The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).
The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
Key finding: Link between hospital-acquired hypernatremia and death
“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.
Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.
Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).
In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).
Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.
Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.
In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.
Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.
“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.
The findings will be presented at the upcoming news conference held by the Endocrine Society
Should sodium be included in a risk calculator for COVID-19?
Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”
Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”
Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.
“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.
“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.
He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”
Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”
Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
Hyper- and hyponatremia linked to adverse COVID-19 outcomes
In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.
The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).
In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.
Overall, hyponatremia was not associated with death (P = .41).
During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.
In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).
The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).
The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
Key finding: Link between hospital-acquired hypernatremia and death
“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.
Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.
Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).
In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).
Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.
Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.
In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.
Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.
“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.
The findings will be presented at the upcoming news conference held by the Endocrine Society
Should sodium be included in a risk calculator for COVID-19?
Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”
Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”
Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.
“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.
“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.
He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”
Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”
Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
Hyper- and hyponatremia linked to adverse COVID-19 outcomes
In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.
The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).
In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.
Overall, hyponatremia was not associated with death (P = .41).
During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.
In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).
The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).
The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
Key finding: Link between hospital-acquired hypernatremia and death
“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.
Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.
Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).
In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).
Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.
Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
USPSTF expands criteria for lung cancer screening
“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.
The updated final recommendations were published online on March 9 in JAMA.
The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.
This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.
The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.
The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.
Uptake has been limited
To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.
The new recommendations will open up screening to many more people, but challenges to implementation remain.
“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”
He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.
In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.
They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.
Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.
“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.
In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.
Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.
“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”
Advocacy needed
When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.
Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.
Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”
Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”
Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”
Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.
“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”
The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.
The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.
A version of this article first appeared on Medscape.com.
“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.
The updated final recommendations were published online on March 9 in JAMA.
The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.
This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.
The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.
The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.
Uptake has been limited
To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.
The new recommendations will open up screening to many more people, but challenges to implementation remain.
“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”
He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.
In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.
They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.
Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.
“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.
In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.
Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.
“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”
Advocacy needed
When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.
Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.
Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”
Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”
Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”
Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.
“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”
The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.
The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.
A version of this article first appeared on Medscape.com.
“This is great news because it means that nearly twice as many people are eligible to be screened, which we hope will allow clinicians to save more lives and help people remain healthy longer,” commented John Wong, MD, chief science officer, vice chair for clinical affairs, and chief of the Division of Clinical Decision Making at USPSTF.
The updated final recommendations were published online on March 9 in JAMA.
The USPSTF recommends annual screening with low-dose CT for adults aged 50-80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.
This updates guidance issued in 2013, which recommended annual screening for lung cancer for adults aged 55-80 years who had a 30 pack-year smoking history and who were either current smokers or had quit within the past 15 years.
The move will nearly double the number of people are now eligible for screening, up to 14.5 million individuals – an increase of 81% (6.4 million adults) from the 2013 recommendations.
The expanded criteria may help increase screening among Black individuals and women. Data show that both groups tend to smoke fewer cigarettes than White men and that Black persons are at higher risk for lung cancer than White persons. In addition, research has shown that about one-third of Black patients with lung cancer were diagnosed before the age of 55 years, which means they would not have been recommended for screening under the previous guidelines.
Uptake has been limited
To date, uptake of lung cancer screening has been very limited, from 6% to 18% of individuals who meet the eligibility criteria.
The new recommendations will open up screening to many more people, but challenges to implementation remain.
“The science is clear that lung cancer screening has the potential to save lives,” Dr. Wong told this news organization. “We recognize that there are existing barriers to screening everyone who is eligible, but clinicians and patients both deserve to know that screening can detect lung cancer early, when treatment has the best chance of being beneficial.”
He added that the hope is that these recommendations will encourage clinicians to examine the barriers to effective lung cancer screening in their communities and to do what they can to improve implementation. “We also hope to encourage patients to have conversations with their clinicians about whether they are eligible for screening and to discuss smoking cessation treatments if they are still smoking,” Dr. Wong added.
In an accompanying editorial, Louise M. Henderson, PhD, M. Patricia Rivera, MD, FCCP, and Ethan Basch, MD, all from the University of North Carolina at Chapel Hill, address some of the current challenges in implementation.
They note that reimbursement for lung cancer screening by Medicare requires submission of data to a Centers for Medicare & Medicaid Services–approved registry, and this can present problems for facilities serving less affluent communities or that have limited resources.
Medicaid coverage is also uneven. As of September 2020, lung cancer screening was covered by 38 Medicaid programs, but not by 9. For three programs, data on coverage were not available.
“With the new recommendations lowering the screening-eligible age to 50 years, many eligible individuals who are uninsured or who are receiving Medicaid and living in states that do not cover screening will have financial barriers to undergo screening,” they write.
In addition, many individuals in at-risk populations lack adequate geographic access to comprehensive lung cancer screening programs.
Expanding eligibility criteria is important, the editorialists point out, but barriers to screening, which include lack of insurance coverage and limited physical access to high-quality screening programs, highlight the complex problems with implementation that need to be addressed.
“A concerted effort to increase the reach of lung cancer screening is needed,” they write. “The 2021 USPSTF recommendation statement represents a leap forward in evidence and offers promise to prevent more cancer deaths and address screening disparities. But the greatest work lies ahead to ensure this promise is actualized.”
Advocacy needed
When approached for comment, Jianjun Zhang, MD, PhD, from the department of thoracic/head and neck medical oncology, University of Texas MD Anderson Cancer Center, Houston, said he supports the new guidelines, and they will lower mortality. “The data are pretty strong overall,” he said in an interview.
Although the uptake of screening is currently very low, he pointed out that, even if uptake remains the same, more lives will be saved because eligibility has been expanded. “More people will be getting screened, so it’s a start,” he said.
Aside from factors such as insurance and access, another problem involves primary care. “Time is very limited in primary care,” he said. “You have about 15 minutes, and it can be really hard to fit everything into a visit. Screening may get left out or may only get a brief mention.”
Advocacy is needed, Dr. Zhang pointed out. “Breast cancer has strong voices and advocacy, and people are more aware of mammography,” he said. “The information is disseminated out into the community. We need the same for lung cancer.”
Dr. Zhang emphasized that, even with the expanded criteria, many individuals will still be missed. “There are other risk factors besides smoking,” he said. “About 10% of lung cancers occur in never-smokers.”
Other risk factors include a family history of lung cancer, exposure to certain materials and chemicals, working in the mining industry, and genetics.
“We will move on to more personalized screening at some point,” he said. “But right now, we can’t make it too complicated for patients and doctors. We need to concentrate on increasing screening rates within these current criteria.”
The updated guidelines have been given a B recommendation, meaning the USPSTF recommends that clinicians provide the service to eligible patients, there is at least fair evidence that this service improves important health outcomes, and benefits outweigh harms.
The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. The original article lists relevant financial relationships of task force members. Dr. Zhang has received grants from Johnson & Johnson and Merck, and adversary/consulting/honoraria fees from AstraZeneca, Bristol-Myers Squibb, GenePlus, Innovent, OrigMed, and Roche.
A version of this article first appeared on Medscape.com.
Missed visits during pandemic cause ‘detrimental ripple effects’
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
according to a new report from the Urban Institute.
Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.
The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.
Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.
Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.
“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.
Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.
In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.
Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.
“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
Lost lives
Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.
“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.
During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.
“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”
Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.
In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
Care most often skipped
The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.
Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).
Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).
The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Call to action on obesity amid COVID-19 pandemic
Hundreds of thousands of deaths worldwide from COVID-19 could have been avoided if obesity rates were lower, a new report says.
An analysis by the World Obesity Federation found that of the 2.5 million COVID-19 deaths reported by the end of February 2021, almost 90% (2.2 million) were in countries where more than half the population is classified as overweight.
The report, released to coincide with World Obesity Day, calls for obesity to be recognized as a disease in its own right around the world, and for people with obesity to be included in priority lists for COVID-19 testing and vaccination.
“Overweight is a highly significant predictor of developing complications from COVID-19, including the need for hospitalization, for intensive care and for mechanical ventilation,” the WOF notes in the report.
It adds that in countries where less than half the adult population is classified as overweight (body mass index > 25 mg/kg2), for example, Vietnam, the likelihood of death from COVID-19 is a small fraction – around one-tenth – of the level seen in countries where more than half the population is classified as overweight.
And while it acknowledges that figures for COVID-19 deaths are affected by the age structure of national populations and a country’s relative wealth and reporting capacity, “our findings appear to be independent of these contributory factors. Furthermore, other studies have found that overweight remains a highly significant predictor of the need for COVID-19 health care after accounting for these other influences.”
As an example, based on the U.K. experience, where an estimated 36% of COVID-19 hospitalizations have been attributed to lack of physical activity and excess body weight, it can be suggested that up to a third of the costs – between $6 trillion and $7 trillion over the longer period – might be attributable to these predisposing risks.
The report said the prevalence of obesity in the United Kingdom is expected to rise from 27.8% in 2016 to more than 35% by 2025.
Rachel Batterham, lead adviser on obesity at the Royal College of Physicians, commented: “The link between high levels of obesity and deaths from COVID-19 in the U.K. is indisputable, as is the urgent need to address the factors that lead so many people to be living with obesity.
“With 30% of COVID-19 hospitalizations in the U.K. directly attributed to overweight and obesity, and three-quarters of all critically ill patients having overweight or obesity, the human and financial costs are high.”
Window of opportunity to prioritize obesity as a disease
WOF says that evolving evidence on the close association between COVID-19 and underlying obesity “provides a new urgency … for political and collective action.”
“Obesity is a disease that does not receive prioritization commensurate with its prevalence and impact, which is rising fastest in emerging economies. It is a gateway to many other noncommunicable diseases and mental-health illness and is now a major factor in COVID-19 complications and mortality.”
The WOF also shows that COVID-19 is not a special case, noting that several other respiratory viruses lead to more severe consequences in people living with excess bodyweight, giving good reasons to expect the next pandemic to have similar effects. “For these reasons we need to recognize overweight as a major risk factor for infectious diseases including respiratory viruses.”
“To prevent pandemic health crises in future requires action now: we call on all readers to support the World Obesity Federation’s call for stronger, more resilient economies that prioritize investment in people’s health.”
There is, it stresses, “a window of opportunity to advocate for, fund and implement these actions in all countries to ensure better, more resilient and sustainable health for all, “now and in our postCOVID-19 future.”
It proposes a ROOTS approach:
- Recognize that obesity is a disease in its own right.
- Obesity monitoring and surveillance must be enhanced.
- Obesity prevention strategies must be developed.
- Treatment of obesity.
- Systems-based approaches should be applied.
A version of this article first appeared on Medscape.com.
Hundreds of thousands of deaths worldwide from COVID-19 could have been avoided if obesity rates were lower, a new report says.
An analysis by the World Obesity Federation found that of the 2.5 million COVID-19 deaths reported by the end of February 2021, almost 90% (2.2 million) were in countries where more than half the population is classified as overweight.
The report, released to coincide with World Obesity Day, calls for obesity to be recognized as a disease in its own right around the world, and for people with obesity to be included in priority lists for COVID-19 testing and vaccination.
“Overweight is a highly significant predictor of developing complications from COVID-19, including the need for hospitalization, for intensive care and for mechanical ventilation,” the WOF notes in the report.
It adds that in countries where less than half the adult population is classified as overweight (body mass index > 25 mg/kg2), for example, Vietnam, the likelihood of death from COVID-19 is a small fraction – around one-tenth – of the level seen in countries where more than half the population is classified as overweight.
And while it acknowledges that figures for COVID-19 deaths are affected by the age structure of national populations and a country’s relative wealth and reporting capacity, “our findings appear to be independent of these contributory factors. Furthermore, other studies have found that overweight remains a highly significant predictor of the need for COVID-19 health care after accounting for these other influences.”
As an example, based on the U.K. experience, where an estimated 36% of COVID-19 hospitalizations have been attributed to lack of physical activity and excess body weight, it can be suggested that up to a third of the costs – between $6 trillion and $7 trillion over the longer period – might be attributable to these predisposing risks.
The report said the prevalence of obesity in the United Kingdom is expected to rise from 27.8% in 2016 to more than 35% by 2025.
Rachel Batterham, lead adviser on obesity at the Royal College of Physicians, commented: “The link between high levels of obesity and deaths from COVID-19 in the U.K. is indisputable, as is the urgent need to address the factors that lead so many people to be living with obesity.
“With 30% of COVID-19 hospitalizations in the U.K. directly attributed to overweight and obesity, and three-quarters of all critically ill patients having overweight or obesity, the human and financial costs are high.”
Window of opportunity to prioritize obesity as a disease
WOF says that evolving evidence on the close association between COVID-19 and underlying obesity “provides a new urgency … for political and collective action.”
“Obesity is a disease that does not receive prioritization commensurate with its prevalence and impact, which is rising fastest in emerging economies. It is a gateway to many other noncommunicable diseases and mental-health illness and is now a major factor in COVID-19 complications and mortality.”
The WOF also shows that COVID-19 is not a special case, noting that several other respiratory viruses lead to more severe consequences in people living with excess bodyweight, giving good reasons to expect the next pandemic to have similar effects. “For these reasons we need to recognize overweight as a major risk factor for infectious diseases including respiratory viruses.”
“To prevent pandemic health crises in future requires action now: we call on all readers to support the World Obesity Federation’s call for stronger, more resilient economies that prioritize investment in people’s health.”
There is, it stresses, “a window of opportunity to advocate for, fund and implement these actions in all countries to ensure better, more resilient and sustainable health for all, “now and in our postCOVID-19 future.”
It proposes a ROOTS approach:
- Recognize that obesity is a disease in its own right.
- Obesity monitoring and surveillance must be enhanced.
- Obesity prevention strategies must be developed.
- Treatment of obesity.
- Systems-based approaches should be applied.
A version of this article first appeared on Medscape.com.
Hundreds of thousands of deaths worldwide from COVID-19 could have been avoided if obesity rates were lower, a new report says.
An analysis by the World Obesity Federation found that of the 2.5 million COVID-19 deaths reported by the end of February 2021, almost 90% (2.2 million) were in countries where more than half the population is classified as overweight.
The report, released to coincide with World Obesity Day, calls for obesity to be recognized as a disease in its own right around the world, and for people with obesity to be included in priority lists for COVID-19 testing and vaccination.
“Overweight is a highly significant predictor of developing complications from COVID-19, including the need for hospitalization, for intensive care and for mechanical ventilation,” the WOF notes in the report.
It adds that in countries where less than half the adult population is classified as overweight (body mass index > 25 mg/kg2), for example, Vietnam, the likelihood of death from COVID-19 is a small fraction – around one-tenth – of the level seen in countries where more than half the population is classified as overweight.
And while it acknowledges that figures for COVID-19 deaths are affected by the age structure of national populations and a country’s relative wealth and reporting capacity, “our findings appear to be independent of these contributory factors. Furthermore, other studies have found that overweight remains a highly significant predictor of the need for COVID-19 health care after accounting for these other influences.”
As an example, based on the U.K. experience, where an estimated 36% of COVID-19 hospitalizations have been attributed to lack of physical activity and excess body weight, it can be suggested that up to a third of the costs – between $6 trillion and $7 trillion over the longer period – might be attributable to these predisposing risks.
The report said the prevalence of obesity in the United Kingdom is expected to rise from 27.8% in 2016 to more than 35% by 2025.
Rachel Batterham, lead adviser on obesity at the Royal College of Physicians, commented: “The link between high levels of obesity and deaths from COVID-19 in the U.K. is indisputable, as is the urgent need to address the factors that lead so many people to be living with obesity.
“With 30% of COVID-19 hospitalizations in the U.K. directly attributed to overweight and obesity, and three-quarters of all critically ill patients having overweight or obesity, the human and financial costs are high.”
Window of opportunity to prioritize obesity as a disease
WOF says that evolving evidence on the close association between COVID-19 and underlying obesity “provides a new urgency … for political and collective action.”
“Obesity is a disease that does not receive prioritization commensurate with its prevalence and impact, which is rising fastest in emerging economies. It is a gateway to many other noncommunicable diseases and mental-health illness and is now a major factor in COVID-19 complications and mortality.”
The WOF also shows that COVID-19 is not a special case, noting that several other respiratory viruses lead to more severe consequences in people living with excess bodyweight, giving good reasons to expect the next pandemic to have similar effects. “For these reasons we need to recognize overweight as a major risk factor for infectious diseases including respiratory viruses.”
“To prevent pandemic health crises in future requires action now: we call on all readers to support the World Obesity Federation’s call for stronger, more resilient economies that prioritize investment in people’s health.”
There is, it stresses, “a window of opportunity to advocate for, fund and implement these actions in all countries to ensure better, more resilient and sustainable health for all, “now and in our postCOVID-19 future.”
It proposes a ROOTS approach:
- Recognize that obesity is a disease in its own right.
- Obesity monitoring and surveillance must be enhanced.
- Obesity prevention strategies must be developed.
- Treatment of obesity.
- Systems-based approaches should be applied.
A version of this article first appeared on Medscape.com.
Pediatric TB – more work needed, especially with HIV-coinfection
Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.
“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.
Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
TB and CLHIV
Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.
Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
Pediatric TB diagnosis
Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.
However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.
In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.
“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
Pediatric TB treatment
Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.
Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.
In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.
Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.
“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.
Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.
Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.
Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.
“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.
Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.
Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.
“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.
Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
TB and CLHIV
Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.
Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
Pediatric TB diagnosis
Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.
However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.
In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.
“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
Pediatric TB treatment
Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.
Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.
In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.
Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.
“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.
Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.
Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.
Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.
“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.
Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.
Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.
“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.
Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
TB and CLHIV
Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.
Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
Pediatric TB diagnosis
Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.
However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.
In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.
“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
Pediatric TB treatment
Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.
Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.
In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.
Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.
“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.
Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.
Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.
Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.
“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.
Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.
FROM CROI 2021
Are long-acting injectables the future of TB treatment?
Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.
“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.
He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
Current TB preventive therapies
Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.
While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
LAI drugs
LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.
The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.
Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.
“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.
Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.
Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.
Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
Considerations for development and implementation
“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.
Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.
Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.
“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).
“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.
“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.
While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.
Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.
Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.
“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.
He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
Current TB preventive therapies
Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.
While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
LAI drugs
LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.
The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.
Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.
“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.
Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.
Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.
Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
Considerations for development and implementation
“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.
Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.
Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.
“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).
“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.
“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.
While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.
Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.
Long-acting injectable (LAI) drug formulations represent a promising new strategy for the prevention and treatment of tuberculosis in women and children, according to an online presentation at the Conference on Retroviruses & Opportunistic Infections, held virtually.
“As a delivery strategy, LAIs hold the potential to unlock a vast chemical space of lipophilic compounds with very potent anti-TB activity that would otherwise not be developed due to poor predicted oral bioavailability,” explained presenter Eric Nuermberger, MD.
He summarized current preventive treatment options for TB and reviewed the potential impact of LAI formulations on TB therapy. In addition, he identified key challenges for future LAI development and proposed a new development path for clinical implementation.
Current TB preventive therapies
Despite widespread availability, the uptake of TB preventive therapy is poor and currently lags behind global targets. One key barrier to widespread uptake is the long duration of treatment, which may hinder patient adherence to therapy.
While shorter preventive regimens, such as 1 month of daily isoniazid plus rifapentine, show similar efficacy and higher completion rates, further shortening of therapy and reducing clinic visits are the most direct methods to increase adherence and treatment completion rates, Dr. Nuermberger said.
LAI drugs
LAI drug formulations allow for slow release of suitable drugs from a depot injected subcutaneously or intramuscularly.
The goal of LAI formulations is to free patients from the daily burden of oral administration. Other potential benefits include better adherence and efficacy, drug exposure, and the potential to overcome intrinsic poor oral bioavailability by bypassing the GI tract entirely.
Potential indications for LAIs include treatment of latent tuberculosis infection (LTBI), and as continuous therapy in people living with HIV in high-burden settings. There is also potential for treating younger children, such as household contacts, who have difficulty taking oral medications.
“We’ve already seen LAIs revolutionize other areas, such as psychiatry and contraception, and we appear to have another revolution in HIV prevention and treatment,” Dr. Nuermberger explained.
Not all existing TB drugs are suitable for LAI formulations, but drugs such as rifapentine, rifabutin, delamanid, and bedaquiline, show more promise than isoniazid or rifampin because of their physiochemical composition. Of all, bedaquiline may offer the best profile for LAI formulation, Dr. Nuermberger said.
Early proof-of-concept in vivo studies have shown potential use of LAI bedaquiline for TB prevention in both drug-sensitive and drug-resistant TB contacts. Translational PK modeling and simulation predicted that a 1-g intramuscular injection of LAI bedaquiline could maintain therapeutic plasma concentrations in humans for greater than 1 month.
Dr. Nuermberger noted that novel diarylquinoline-based therapies, currently in phase 1 studies, may be even better candidates for LAI-based TB preventive therapy. Early data suggests these compounds may be 10-20 times more potent and have a lower CV risk profile than that of bedaquiline.
Considerations for development and implementation
“Despite the promising potential of long-acting injectables for TB, we are still in the very early stages,” said Dr. Nuermberger.
Ensuring and optimizing acceptance of LAI formulations, especially in at-risk populations, will be very important, he explained. Early involvement of children and pregnant women in studies of who may benefit most from LAI drugs will also be essential.
Other important considerations include cost-effectiveness, particularly in at-risk and vulnerable populations. Furthermore, new dedicated research and development programs are needed to continue to develop more drug candidates suitable for LAI.
“Long-acting formulations hold enormous promise to be transformative for combating TB, through simplification of delivery and overcoming issues of adherence that can compromise success of current interventions,” said Andrew Owen, PhD, of the University of Liverpool (England).
“The ability to deliver an entire course of drug in a single visit promises to ensure missed doses don’t compromise outcomes or place unnecessary selective pressure in favor of drug resistance,” Dr. Owen said.
“Recent studies showing the value of one-month oral treatment regimens for LTBI make long-acting formulations seem more realistic and drugs such as long-acting bedaquiline put a one-shot regimen within reach,” Charles W. Flexner, MD, of Johns Hopkins University, Baltimore, said in an interview.
While no LAIs have been approved for TB, Dr. Nuermberger was optimistic that the recent success of LAI formulations for HIV treatment and prevention will catalyze further efforts in the TB landscape.
Dr. Nuermberger disclosed research support from Janssen Pharmaceuticals, TB Alliance, and the Gates Medical Research Institute. The presentation was sponsored by Janssen Pharmaceuticals, Johns Hopkins CFAR, NIH, Unitaid, and the TB Alliance.
FROM CROI 2021
Asthma-COPD overlap linked to occupational pollutants
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
The development and worsening of overlapping asthma and chronic obstructive pulmonary disease (COPD) can be affected by pollutants found in rural and urban environments, according to a recent presentation at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year.
“ features,” Jill A. Poole, MD, division chief of allergy and immunology at the University of Nebraska Medical Center, Omaha, said in her presentation.
The Global Initiative for Asthma (GINA) first outlined a syndrome in 2015 described as “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD” and called asthma-COPD overlap syndrome. In 2017, a joint American Thoracic Society/National Heart, Lung, and Blood Institute workshop outlined knowledge gaps about asthma-COPD overlap, noting it “does not represent a single discrete disease entity.”
“This is not a single disease and should be thought of as being heterogeneous and used as a descriptive label for patients commonly seen in clinical practice,” Dr. Poole said. “Both asthma and COPD definitions are not mutually exclusive because each disease includes several phenotypes with different underlining mechanisms.” An example of how asthma-COPD overlap might present is through a patient with allergic asthma who has a history of smoking who develops airflow obstruction that isn’t fully reversible, or a patient with COPD “with high reversible airflow, obstruction, type 2 inflammation, and perhaps the presence of peripheral blood eosinophils or sputum eosinophils.”
A patient’s interaction with urban, rural, and occupational environments may additionally impact their disease, Dr. Poole explained. “The environmental factors of an urban versus rural environment may not be necessarily mutually exclusive,” she said. “It’s also important to recognize occupational exposures that can be both seen in an urban or rural environment [can] contribute to asthma-COPD overlap.”
In a study of 6,040 men and women with asthma living in Canada, 630 (10.4%) had asthma-COPD overlap, with increased air pollution raising the likelihood of developing asthma-COPD overlap (odds ratio, 2.78; 95% confidence interval, 1.62-4.78). These people experienced later onset asthma, increased emergency department visits before a diagnosis of COPD, and increased mortality. Another study in Canada of women from Ontario in the Breast Cancer Screening Study found 1,705 of 4,051 women with asthma also had COPD. While air pollution did not increase the risk of developing asthma-COPD overlap, there was an association between body mass index, low level of education, living in a rural area, and smoking status.
Among farmers in rural areas, “it has been recognized that there is something called the asthma-like syndrome that’s been reported in adult farming communities,” Dr. Poole said, which includes “some degree of airflow obstruction and reversibility” that can be worsened by smoking and could be an overlap of asthma and COPD. Farmers can also experience asthma exacerbations while working, and “livestock farmers appear more at risk of developing [chronic bronchitis and/or COPD] than do the crop farmers,” she noted.
Occupational environments outside of agriculture exposure can cause incident asthma, with high-molecular-weight antigens such as flour cereal, animal dander, latex, psyllium, crab processing products, and enzymes as well as low-molecular-weight antigens such as isocyanates, woods, antibiotics, glues, epoxies colophony products, and dyes presenting a risk. In food processing, main allergen sources can include raw and processed animal and plant products, additives and preservatives, contaminants from microbes or insects, inhaled dust particles or aerosols, which can be “IgE mediated, mixed IgE-mediated and non-lgE mediated.”
While some studies have been conducted on the prevalence of work-related asthma and asthma-COPD overlap, “in general, the prevalence and clinical features have been scarcely investigated,” Dr. Poole said. One survey of 23,137 patients found 52.9% of adults with work-related asthma also had COPD, compared with 25.6% of participants whose asthma was not work related.
To prevent asthma-COPD overlap, Dr. Poole recommended tobacco cessation, reducing indoor biomass fuel use, medical surveillance programs such as preplacement questionnaires, and considering “reducing exposure to the respiratory sensitizers with ideally monitoring the levels to keep the levels below the permissible limits.”
Dr. Poole noted there is currently no unique treatment for asthma-COPD overlap, but it is “important to fully characterize and phenotype your individual patients, looking for eosinophilia or seeing if they have more neutrophil features and whether or not the allergy features are prevalent and can be treated,” she said. “[A]wareness is really required such that counseling is encouraged for prevention and or interventional strategies as we move forward.”
For patients with features of both asthma and COPD where there is a high likelihood of asthma, treat the disease as if it were asthma, Dr. Poole said, but clinicians should follow GINA GOLD COPD treatment recommendations, adding on long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) when needed, but avoiding LABAs and/or LAMAs without use of inhaled corticosteroids, and avoiding oral corticosteroids entirely. Clinicians should be reviewing the treatments of patients with asthma and COPD features “every 2-3 months to see how their response is to it, and what additional therapies could be used,” she said.
Dr. Poole reports receiving grant support from National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, and the Central States Center for Agricultural Safety and Health at the University of Nebraska Medical Center.
FROM AAAAI 2021
Cannabis vaping triggers respiratory symptoms in teens
, according to findings of a study based on a national sample of teens.
Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.
“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.
In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
Any cannabis vaping makes impact
In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).
Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.
The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.
However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.
The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
Product details aid in diagnosis
“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said.
Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said.
The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.
As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.
The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.
Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.
, according to findings of a study based on a national sample of teens.
Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.
“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.
In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
Any cannabis vaping makes impact
In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).
Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.
The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.
However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.
The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
Product details aid in diagnosis
“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said.
Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said.
The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.
As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.
The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.
Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.
, according to findings of a study based on a national sample of teens.
Most studies of electronic nicotine delivery systems (ENDS) use in teens have not addressed cannabis vaping, although e-cigarette– or vaping product use–associated lung injury (EVALI) has been predominately associated with cannabis products, wrote Carol J. Boyd, PhD, of the University of Michigan School of Nursing, Ann Arbor, and colleagues.
“At this time, relatively little is known about the population-level health consequences of adolescents’ use of ENDS, including use with cannabis and controlling for a history of asthma,” they said.
In a study published in the Journal of Adolescent Health, the researchers identified 14,798 adolescents aged 12-17 years using Wave 4 data from the Population Assessment of Tobacco and Health Study. Of these, 17.6% had a baseline asthma diagnosis, 8.9% reported ever using cannabis in ENDS, and 4.7% reported any cannabis use. In addition, 4.2% reported current e-cigarette use, 3.1% reported current cigarette use, 51% were male, and 69.2% were white.
Any cannabis vaping makes impact
In a fully-adjusted model, teens who had ever vaped cannabis had higher odds of five respiratory symptoms in the past year, compared with those with no history of cannabis vaping: wheezing or whistling in the chest (adjusted odds ratio, 1.81); sleep disturbed by wheezing or whistling (AOR, 1.71); speech limited because of wheezing (AOR, 1.96); wheezy during and after exercise (AOR, 1.33), and a dry cough at night independent of a cold or chest infection (AOR, 1.26).
Neither e-cigarettes nor cigarettes were significantly associated with any of these five respiratory symptoms in the fully adjusted models. In addition, “past 30-day use of cigarettes, e-cigarettes and cannabis use were associated with some respiratory symptoms in bivariate analyses but not in the adjusted models,” the researchers noted. In addition, the associations of an asthma diagnosis and respiratory symptoms had greater magnitudes than either cigarette, e-cigarette, and cannabis use or vaping cannabis with ENDS.
The study findings were limited by several factors including the inherent limitations of secondary database analysis, the researchers noted. “Another limitation is that co-use of cannabis and tobacco/nicotine was not assessed and, in the future, should be examined: Researchers have found that co-use is related to EVALI symptoms among young adults,” they said.
However, the study is the first known to include ENDS product use and respiratory symptoms while accounting for baseline asthma, and an asthma diagnosis was even more strongly associated with all five respiratory symptoms, the researchers said.
The results suggest that “the inhalation of cannabis via vaping is associated with some pulmonary irritation and symptoms of lung diseases (both known and unknown),” that may be predictive of later EVALI, they concluded.
Product details aid in diagnosis
“As we continue to see patients presenting with EVALI in pediatric hospitals, it is important for us to identify if there are specific products (or categories) that are more likely to cause it,” said Brandon Seay, MD, FCCP, a pediatric pulmonologist and sleep specialist at Children’s Healthcare of Atlanta, in an interview. “When we are trying to diagnose EVALI, we should be asking appropriate questions about exposures to specific products to get the best answers. If we simply ask ‘Are you smoking e-cigarettes?’ the patient may not [equate] e-cigarette smoking to vaping cannabis products,” he said.
Dr. Seay said he was not surprised by the study findings. “A lot of the patients I see with EVALI have reported vaping THC products, and most of them also report that the products were mixed by a friend or an individual instead of being a commercially produced product,” he noted. “This is not surprising, as THC is still illegal in most states and there would not be any commercially available products,” he said. “The mixing of these products by individuals increases the risk of ingredients being more toxic or irritating to the lungs,” Dr. Seay added. “This does highlight the need for more regulation of vaping products. As more states legalize marijuana, more of these products will become available, which will provide an opportunity for increased regulation, he said.
The take-home message for clinicians is to seek specific details from their young patients, Dr. Seay emphasized. “When we are educating our patients on the dangers of vaping/e-cigarettes, we need to make sure we are asking specifically which products they are using and know the terminology,” he said. “The use of THC-containing products will be increasing across the country with more legalization, so we need to keep ourselves apprised of the different risks between THC- and nicotine-containing devices,” he added.
As for additional research, it would be interesting to know whether patients were asked where they had gotten their products (commercially available products vs. those mixed by individuals) and explore any difference between the two, said Dr. Seay. “Also, as these products are relatively new to the market, compared to cigarettes, data on the longitudinal effects of vaping (nicotine and THC) over a long period of time, compared to traditional combustible cigarettes, will be needed,” he said.
The study was funded by grants from the National Institutes of Health, National Institute on Drug Abuse, and National Cancer Institute. The researchers had no financial conflicts to disclose.
Dr. Seay had no financial disclosures, but serves as a member of the CHEST Physician editorial board.
FROM THE JOURNAL OF ADOLESCENT HEALTH
Tocilizumab (Actemra) scores FDA approval for systemic sclerosis–associated interstitial lung disease
The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.
Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.
The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.
In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).
The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.
Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.
Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.
Prescribing information is available here.
The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.
Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.
The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.
In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).
The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.
Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.
Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.
Prescribing information is available here.
The Food and Drug Administration has approved subcutaneously-injected tocilizumab (Actemra) to reduce the rate of pulmonary function decline in systemic sclerosis–associated interstitial lung disease (SSc-ILD) patients, according to a press release from manufacturer Genentech.
Tocilizumab is the first biologic to be approved by the agency for adults with SSc-ILD, a rare and potentially life-threatening condition that may affect up to 80% of SSc patients and lead to lung inflammation and scarring.
The approval was based primarily on data from a phase 3 randomized, double-blind, placebo-controlled clinical trial (the focuSSced trial) that included 212 adults with SSc. Although that study failed to meet its primary endpoint of change from baseline to 48 weeks in the modified Rodnan Skin Score, the researchers observed a significantly reduced lung function decline as measured by forced vital capacity (FVC) and percent predicted forced vital capacity (ppFVC) among tocilizumab-treated patients, compared with those who received placebo. A total of 68 patients (65%) in the tocilizumab group and 68 patients (64%) in the placebo group had SSc-ILD at baseline.
In a subgroup analysis, patients taking tocilizumab had a smaller decline in mean ppFVC, compared with placebo patients (0.07% vs. –6.4%; mean difference, 6.47%), and a smaller decline in FVC (mean change –14 mL vs. –255 mL with placebo; mean difference, 241 mL).
The mean change from baseline to week 48 in modified Rodnan Skin Score was –5.88 for patients on tocilizumab and –3.77 with placebo.
Safety data were similar between tocilizumab and placebo groups through 48 weeks, and similar for patients with and without SSc-ILD. In general, tocilizumab side effects include increased susceptibility to infections, and serious side effects may include stomach tears, hepatotoxicity, and increased risk of cancer and hepatitis B, according to the prescribing information. However, the most common side effects are upper respiratory tract infections, headache, hypertension, and injection-site reactions.
Tocilizumab, an interleukin-6 receptor antagonist, is already approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis, as well as for adult patients with giant cell arteritis; patients aged 2 years and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis; and adults and pediatric patients 2 years of age and older with chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome.
Prescribing information is available here.