Federal Practitioner

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

Oncology will account for a substantial majority of clinical trials to be launched in 2020, as well as accounting for most of those to be completed this year, according to a new analysis.

“A large number of early stage clinical trials within this field are likely to be due to the demand for novel therapeutic approaches addressing unmet medical need,” commented Mohamed Abukar, pharma analyst at GlobalData.

Most oncology studies planned to start in 2020 are phase 1 and 2, and 61.9% are industry sponsored. Eli Lilly and Novartis have announced the most upcoming studies.

Among the new drugs being evaluated in these clinical trials, four of the top seven drugs in phase 1–3 development are monoclonal antibodies, with the most studies being conducted on the experimental agents ZW25 (Zymeworks) and KSI-301 (Kodiak Sciences), the report notes.

As for clinical trials due for completion this year, many are funded by nonindustry sources, with Memorial Sloan Kettering Cancer Center accounting for the most number of trials.

Top Indications Explored in Clinical Trials

Oncology also accounts for eight of the top ten indications for clinical trials planned to start in 2020, with solid tumors, breast cancer, and non–small cell lung cancer accounting for the second, third, and fourth top spots, respectively, regardless of sponsor type.

However, for industry-sponsored clinical trials, the predominant area is solid tumors for new investigations to start this year, followed by breast cancer, then pain.

“This is attributed to the manner in which the burden of cancer worldwide necessitates industry investment to allow for capitalization on the increasing market size,” Abukar said.

This article first appeared on Medscape.com.

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

[email protected]

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

[email protected]

Vice President Mike Pence will be the White House point person quarterbacking the administration’s response to COVID-19, although President Donald Trump was quick to dismiss the notion that he is a so-called coronavirus “czar.”

WhiteHouse.gov

President Trump introduced Vice President Pence in this role during a Feb. 26 press conference. The same night, officials at the Centers for Disease Control and Prevention announced the first case of possible community spread of the novel coronavirus in the United States.

“I am going to be putting our vice president, Mike Pence, in charge, and Mike will be working with the professionals, the doctors, and everybody else that is working” on this, President Trump said.

“Mike is going to be in charge and Mike will report back to me, but he’s got a certain talent for this,” President Trump continued, noting that while Vice President Pence was governor of Indiana, his was the first state to have a patient affected by the 2014 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak, so he has experience in a similar situation.

“I know full well the importance of presidential leadership, the importance of administration leadership, and the vital role of partnerships of state and local governments and health authorities in responding to the potential threat of dangerous infectious diseases,” Vice President Pence said.

He said that his role will be to continue to meet with the Coronavirus Task Force and bring to the president “the best options for action and to see to the safety and well being and health of the American people. I will also be continuing to reach out to governors [and] state and local officials.”

Vice President Pence said he will also be working with Congress to ensure that resources are available.

It was noted during the press conference that some members of Congress consider the $2.5 billion in emergency appropriations requested by the White House to be inadequate and that the legislative branch is working to provide more funding.

Vice President Pence’s new role does not change the command structure of the Coronavirus Task Force, which is currently led by Department of Health & Human Services Secretary Alex Azar.

Speaking at the press conference, Secretary Azar noted that he is still chairman of the task force. “Having the vice president gives me the biggest stick one can have in the government on this whole-of-government approach.”

He emphatically stated, “not in the least,” in response to a question about whether he felt he was being replaced. “When this was mentioned to me, I said I was delighted that I get to have the vice president helping in this way. Delighted.”

The announcement came as President Trump continued to downplay the threat of the coronavirus to U.S. citizens, going so far as to contradict CDC officials who have stated that it is a matter of when, not if, there will be community spread in the United States.

“I don’t think it’s inevitable,” President Trump said. “I think that there’s a chance that it could get worse. There’s a chance it could get fairly substantially worse, but nothing’s inevitable.”

Immediately after President Trump wrapped up his statement, however, the CDC formally announced the first case of possible community spread of the coronavirus. In a statement issued to the press, the agency announced the 15th confirmed case in the United States, a person in California “who reportedly did not have relevant travel history or exposure to another known patient” with the coronavirus.

“This case was detected through the U.S. public health system – picked up by astute clinicians,” CDC added, noting it will continue to provide updates on the evolving situation.

[email protected]

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Vaccination against the Ebola virus is recommended for first responders, health care personnel, and laboratory workers deemed at high risk of exposure, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

The committee voted unanimously to recommended pre-exposure vaccination with the rVSVdeltaG-ZEBOV-GP vaccine for adults aged 18 years and older who are at potential risk of exposure to the Ebola species Zaire ebolavirus because they fall into any of the following three categories:

• They are responding to an outbreak of Ebola virus disease.
• They are working as health care personnel at a federally designated Ebola Treatment Center in the United States.
• The are working in laboratories or are other staff members at biosafety-level 4 facilities in the United States.

Mary Choi, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) presented data on the safety and effectiveness of the vaccine and the work group considerations in recommending vaccination in the three target populations.

In clinical trials, the most commonly reported adverse events associated with the vaccine were arthritis and arthralgia, Dr. Choi said, but the duration of those cases was limited to months and did not persist long term.

Pre-exposure vaccination for health care personnel, laboratory workers, and support staff would provide an additional layer of protection, she explained, in addition to existing safeguards such as personal protective equipment and engineering controls at the facility. The work group’s research showed that most of the target population believed that the desirable effects of that protection outweigh potentially undesirable effects, Dr. Choi noted.

Some committee members expressed concerns about vaccination of pregnant women. But the recommendations are presented as “population based, not shared decision making,” said Sharon E. Frey, MD, of Saint Louis University in St. Louis, Missouri.

Several members noted that pregnant women should not be automatically included or excluded from vaccination if they fall into a high-risk population. And the committee agreed that additional guidance in the policy note will help assess risk and that organizations will determine the risk for their employees and whether to offer the vaccine.

The FDA approved the currently available U.S. vaccine for Ebola in 2019. Merck manufactures that vaccine.

The ACIP members had no relevant financial conflicts to disclose.

Researchers have developed chimeric antigen receptor (CAR) T cells expressing a fully human antibody against CD229, a surface antigen that shows universal and strong tumor expression in patients with multiple myeloma (MM). These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.

Wikimedia Commons/KGH/Creative Commons License

This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.

Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.

Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.

“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229^high T cells, they spare functional CD229^neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.

The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.

[email protected]

SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.

Researchers have developed chimeric antigen receptor (CAR) T cells expressing a fully human antibody against CD229, a surface antigen that shows universal and strong tumor expression in patients with multiple myeloma (MM). These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.

Wikimedia Commons/KGH/Creative Commons License

This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.

Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.

Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.

“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229^high T cells, they spare functional CD229^neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.

The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.

[email protected]

SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.

Researchers have developed chimeric antigen receptor (CAR) T cells expressing a fully human antibody against CD229, a surface antigen that shows universal and strong tumor expression in patients with multiple myeloma (MM). These cells proved to be active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells, according to a report in Nature Communications.

Wikimedia Commons/KGH/Creative Commons License

This research is important because most MM patients eventually succumb to the disease and previously developed CAR T cells targeting B-cell maturation antigen (BCMA) on MM cells have shown high-response rates but limited durability.

Previous research showed that CD229/LY9 is a potential target for CAR T-cell therapy in MM because of its strong and homogeneous expression on the bulk of tumor cells, as well as chemotherapy-resistant myeloma progenitors; its absence from most normal cells; and dependence of MM cells on CD229 for their survival, according to Sabarinath V. Radhakrishnan, MD, of the University of Utah, Salt Lake City, and colleagues.

Using primary CD138+ tumor cells from three patients with plasma cell leukemia, a highly aggressive form of MM, which all showed high expression of CD229, the researchers found that CD229 CAR T cells exhibited high cytotoxic activity against these cells. In addition, when assessing two MM cell lines, U-266 and RPMI-8226, expressing different levels of CD229, they found that CD229 CAR T cells efficiently killed both cell lines in vitro.

“We do not observe fratricide during CD229 CAR T-cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229^high T cells, they spare functional CD229^neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM,” the authors concluded.

The study was funded by several nongovernmental organizations and the National Cancer Institute. Three of the authors are inventors on PCT application US2017/42840 “Antibodies and CAR T Cells for the Treatment of Multiple Myeloma” describing the therapeutic use of CD229 CAR T cells.

[email protected]

SOURCE: Radhakrishnan SV et al. Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
 

Avoiding one in four events

Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.

Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.

“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.

Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.

Clinically validating results

“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.

Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.

“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”

The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.

This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.

Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.

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

SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.
 

Avoiding one in four events

Assessing the French participants in the TST trial showed that targeting LDL below 70 mg/dL for more than 5 years avoided more than one in four subsequent major cardiovascular events among adults who experienced a recent ischemic stroke or TIA.

Furthermore, more intense LDL lowering also avoided more than one in four recurrent cerebral infarctions or urgent carotid revascularizations following a TIA, as well as one in four recurrent cerebral infarctions or hemorrhages (all strokes), compared with the higher LDL target.

“This was obtained without increasing the risk of intracranial hemorrhage with a number needed to treat of 30,” the researchers noted. “In the context of all randomized clinical trials with statin and other lipid-lowering drugs, there is no reason to think that Asian patients do not benefit from statin treatment and from a lower target LDL cholesterol,” the researchers added.

Therefore, they plan to continue assessing the 742 Korean participants until they reach a median of 5 years of follow-up.

Clinically validating results

“My feeling is that these data are highly supportive of a practice that many of us have been using for years without this level of evidence,” Mitchell S.V. Elkind, MD, said when asked to comment on the study.

Prior secondary analyses of studies, including research into patients with intracranial atherosclerosis, demonstrated benefit from treating to this lower LDL cholesterol target. “These studies were suggestive enough that many of us were treating patients aggressively with statins,” added Dr. Elkind, professor of neurology and epidemiology and chief of the division of neurology clinical outcomes research and population sciences at Columbia University in New York.

“But this really confirms that [fact] with clinical trial evidence,” said Dr. Elkind, “and I think will be very useful to us as clinicians.”

The results could be used to counsel patients about the potential benefits of statin therapy or to motivate primary care providers to treat patients more aggressively, said Dr. Elkind, who will begin his term as president of the American Heart Association/American Stroke Association in July.

This study was supported by a grant from the French Ministry of Health and from SOS-Attaque Cérébrale Association, with unrestricted grants from Pfizer, AstraZeneca, and Merck for French sites and from Pfizer for South Korean sites.

Dr. Amarenco receives research grant support and consulting fees from Pfizer, Merck, and AstraZeneca. Elkind had has disclosed no relevant financial relationships.

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

SOURCE: Amarenko P et al. ISC 2020. Late-breaking abstract 9.

LOS ANGELES – In a subanalysis of the TST (Treat Stroke to Target) trial, restricting analysis to only French participants followed for an average of 5 years demonstrated an even more robust potential to reduce recurrent stroke and other major cardiovascular events by treating patients to an LDL target of below 70 mg/dL. Treating LDL to a mean of 66 mg/dL versus 96 mg/dL was associated with a 26% relative risk reduction for the composite endpoint of ischemic stroke, MI, new symptoms requiring urgent coronary or carotid revascularization, and vascular death in an adjusted analysis.

“The results are similar to the main paper but even more spectacular, with no increase in hemorrhagic stroke whatsoever, and positive results on any stroke,” study investigator Pierre Amarenco, MD, professor and chair of the department of neurology and Stroke Centre, Bichat University Hospital, Paris, said.

Dr. Amarenco presented the findings as a late-breaking abstract at the International Stroke Conference sponsored by the American Heart Association. The trial was published simultaneously in the journal Stroke.

In the full TST trial population, risk was reduced by 22% with more-aggressive LDL-lowering treatment, compared with the more lax 90-110 mg/dL target.

The TST cohort included both French and Korean participants. Dr. Amarenco and colleagues focused on the French population in the current study because the group was larger (2,148 vs. 742 Korean participants) and had a longer follow-up, an average of 5.3 years compared to 2.0 years among Korean patients. The initial study had shown “very significant results in the French patients and no apparent effect in Korean patients,” he said. The longer duration of treatment in the French cohort could have contributed to the greater risk reduction, said Dr. Amarenco.

A 2017 European Atherosclerosis Society Consensus Panel statement noted that exposure time to lipid-lowering drugs correlates with outcomes. The European Stroke Organization and the American Heart Association/American Stroke Association guidelines each recommend intensive statin treatment to lower serum lipids following an ischemic stroke of atherosclerotic origin or after a transient ischemic attack (TIA). However, the current researchers noted that the recommendations do not specify specific target numbers.

“Therefore, there is uncertainty about the target levels of LDL cholesterol,” he said.
 

Aiming at different targets

To learn more, Dr. Amarenco and colleagues randomly assigned 1,073 of the French patients to a target LDL treatment group of 70 mg/dL and another 1,075 to a target range of 90-110 mg/dL. They enrolled participants at 61 sites in France. Mean age was 67 years. All participants had experienced an ischemic stroke within 3 months or a TIA within 15 days of baseline. They presented either with a modified Rankin Scale poststroke score of 0-3 or a TIA that included at least arm and leg motor deficit or speech disturbance that lasted more than 10 minutes.

Investigators could use any type and any dose of statin to reach the respective targets. Statins could be prescribed as monotherapy or in combination with ezetimibe (Zetia) or other agents. The baseline mean LDL cholesterol level was 137 mg/dL in the lower target group and 138 mg/dL in the higher target group, respectively (3.5 mmol/L in both groups). Dr. Amarenco and colleagues measured LDL cholesterol levels at 3 weeks postrandomization and then every 6 months.

A smaller proportion of the lower LDL cholesterol target group experienced the adverse composite outcome, 9.6%, compared with 12.9% of the higher LDL cholesterol target group. This translated to a hazard ratio of 0.73 (95% confidence interval, 0.57-0.94; P = .015). The absolute risk reduction was 3.3% with a number needed to treat of 30.

An analysis adjusted for covariates showed a hazard ratio of 0.74 (95% CI, 0.57-0.95; P = .019).

Cerebral infarction and acute cerebral artery revascularization were reduced by 27% (HR, 0.73; 95% CI, 0.54-0.99; P = .046). Cerebral infarction or intracranial hemorrhage (all strokes) were reduced by 28% (HR, 0.72; 95% CI, 0.54-0.98; P = .023). In this case, there was an absolute risk reduction of 2.9% and a number needed to treat of 34.

In contrast, MI or urgent coronary revascularization following new symptoms were not significantly reduced (HR, 0.66; 95% CI, 0.67-1.20; P = .18). The investigators also reported nonsignificant results regarding vascular death (HR, 0.76; 95% CI, 0.44-1.32; P = .32] and all deaths (HR, 1.0; 95% CI, 0.74-1.35; P = .99).

Dr. Amarenco and colleagues also tracked adverse events. They found intracranial hemorrhage occurred in 13 (1.2%) patients assigned an LDL cholesterol below 70 mg/dL and in 11 (1%) patients assigned an LDL cholesterol of 100 ± 10 mg/dL. In this analysis, the hazard ratio was 1.17 (95% CI, 0.53-2.62; P = .70), and the absolute difference was 0.2%.

The investigators also reported that 10.3% of the lower LDL target group vs 13.6% of the higher LDL target group experienced either the primary outcome or intracranial hemorrhage. This translated to a 25% relative risk reduction (HR, 0.75; 95% CI, 0.58-0.96; P = .021), an absolute risk reduction of 3.3% and a number needed to treat of 30.