User login
FDA approves new drug for CLL/SLL and follicular lymphoma
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.
who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.
Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.
The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.
The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).
Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.
The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.
The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.
Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.
The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.
Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.
Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.
New Edition of the ‘Go-To’ Book on Diabetes Available
“Diabetes in America was written to serve as the go-to book for anything you ever wanted to know about diabetes,” says Catherine Cowie, PhD, editor and senior advisor for the National Institute of Diabetes and Digestive and Kidney Diseases’ Diabetes Epidemiology Program. “It’s a resource for everyone, because diabetes affects just about everyone.”
Written by recognized experts who “represent every facet of diabetes,” the book covers relevant research, data and trends, complications and related conditions, and prevention and medical care. It is “rich in data,” says Dr. Cowie, and includes cross-sectional national data, as well as smaller geographic community and longitudinal studies. This edition includes both published and unpublished data that were specifically analyzed for the book.
Clinical trial data are summarized to show the strongest evidence available for the effectiveness of interventions, but the book also emphasizes “points of hope” found through research: For example, people at high risk can prevent or delay type 2 diabetes by losing a modest amount of weight, and rates of some complications, such as lower extremity amputations, are on the decline.
Cowie says Diabetes in America is designed to be useful to a variety of readers. Patients can use it to better understand their condition or risk factors; practitioners can use it to assess patients’ risk of diabetes and associated complications; health policy makers who need “sound quantitative knowledge” can use it to guide decision making; scientists can use it to help identify areas of needed research.
To download, visit: https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-3rd-edition.
“Diabetes in America was written to serve as the go-to book for anything you ever wanted to know about diabetes,” says Catherine Cowie, PhD, editor and senior advisor for the National Institute of Diabetes and Digestive and Kidney Diseases’ Diabetes Epidemiology Program. “It’s a resource for everyone, because diabetes affects just about everyone.”
Written by recognized experts who “represent every facet of diabetes,” the book covers relevant research, data and trends, complications and related conditions, and prevention and medical care. It is “rich in data,” says Dr. Cowie, and includes cross-sectional national data, as well as smaller geographic community and longitudinal studies. This edition includes both published and unpublished data that were specifically analyzed for the book.
Clinical trial data are summarized to show the strongest evidence available for the effectiveness of interventions, but the book also emphasizes “points of hope” found through research: For example, people at high risk can prevent or delay type 2 diabetes by losing a modest amount of weight, and rates of some complications, such as lower extremity amputations, are on the decline.
Cowie says Diabetes in America is designed to be useful to a variety of readers. Patients can use it to better understand their condition or risk factors; practitioners can use it to assess patients’ risk of diabetes and associated complications; health policy makers who need “sound quantitative knowledge” can use it to guide decision making; scientists can use it to help identify areas of needed research.
To download, visit: https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-3rd-edition.
“Diabetes in America was written to serve as the go-to book for anything you ever wanted to know about diabetes,” says Catherine Cowie, PhD, editor and senior advisor for the National Institute of Diabetes and Digestive and Kidney Diseases’ Diabetes Epidemiology Program. “It’s a resource for everyone, because diabetes affects just about everyone.”
Written by recognized experts who “represent every facet of diabetes,” the book covers relevant research, data and trends, complications and related conditions, and prevention and medical care. It is “rich in data,” says Dr. Cowie, and includes cross-sectional national data, as well as smaller geographic community and longitudinal studies. This edition includes both published and unpublished data that were specifically analyzed for the book.
Clinical trial data are summarized to show the strongest evidence available for the effectiveness of interventions, but the book also emphasizes “points of hope” found through research: For example, people at high risk can prevent or delay type 2 diabetes by losing a modest amount of weight, and rates of some complications, such as lower extremity amputations, are on the decline.
Cowie says Diabetes in America is designed to be useful to a variety of readers. Patients can use it to better understand their condition or risk factors; practitioners can use it to assess patients’ risk of diabetes and associated complications; health policy makers who need “sound quantitative knowledge” can use it to guide decision making; scientists can use it to help identify areas of needed research.
To download, visit: https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-3rd-edition.
NICE looks likely to reject use of Kymriah for DLBCL
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
The National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending against tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).
Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.
Tisagenlecleucel is also European Commission–approved to treat patients up to age 25 years who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse posttransplant, or in second or later relapse.
In September 2018, the National Health Service (NHS) in England announced tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.
However, in who have received two or more lines of systemic therapy. NICE noted that there is no standard treatment for this patient group, and that salvage chemotherapy is the most common treatment option.
Although the latest results from the JULIET trial suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy. Additionally, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.
All cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.
The list price for tisagenlecleucel is 282,000 pounds. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.
In August, NICE issued a similar draft guidance document recommending against use of another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta). Axicabtagene ciloleucel is approved in Europe for the treatment of patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.
Troponin I: Powerful all-cause mortality risk marker in COPD
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
PARIS – High relative even after researchers adjusted for all major cardiovascular and COPD prognostic indicators, according to a late-breaker presentation at the annual congress of the European Respiratory Society.
Troponin I is detectable in the plasma of most patients with COPD, but relative increases in troponin I correlate with greater relative increases in most cardiovascular and COPD risk factors, according to Benjamin Waschki, MD, Pulmonary Research Institute, LungenClinic, Grosshansdorf, Germany.
The relationship between increased troponin I and increased all-cause mortality was observed in an on-going prospective multicenter cohort of COPD patients followed at 31 centers in Germany. The cohort is called COSYCONET and it began in 2010. The current analysis evaluated 2,020 COPD patients without regard to stage of disease.
There were 136 deaths over the course of follow-up. Without adjustment, the hazard ratio (HR) for death was more than twofold higher in the highest quartile of troponin I (equal to or greater than 6.6 ng/mL), when compared with the lowest (under 2.5 ng/mL) (HR, 2.42; P less than .001). Graphically, the mortality curves for each of the quartiles began to separate at about 12 months, widening in a stepwise manner for greater likelihood of death from the lowest to highest quartiles.
The risk of death from any cause remained elevated for the highest relative to lowest troponin I quartiles after adjusting for cardiovascular risk factors and after adjusting for COPD severity. Again, there was a distinct stepwise separation of the mortality curves for each higher troponin quartile,
Of particular importance, troponin I remained predictive beyond the BODE index, which is a currently employed prognostic mortality predictor in COPD, according to Dr. Waschki. When defining elevated troponin as greater than 6 ng/ML and a high BODE score as greater than 4, mortality was higher for those with a high BODE and low troponin than a high troponin and low BODE, (P less than .001), but a high troponin I was associated with a higher risk of mortality when BODE was low (P less than .001). Moreover, when both troponin I and BODE were elevated, all-cause mortality was more than doubled, relative to those without either risk factor (HR, 2.56; P = .003), Dr. Waschki reported.
After researchers adjusted for major cardiovascular risk factors, such as history of MI and renal impairment, and for major COPD risk factors, such as 6-minute walk test and BODE index, those in the highest quartile had a more than 50% greater risk of death relative to those in the lower quartile over the 3 years of follow-up (HR, 1.69; P = .007), according to Dr. Waschki.
Although troponin I is best known for its diagnostic role in MI, it is now being evaluated as a risk stratifier for many chronic diseases, such as heart failure and chronic kidney disease, explained Dr. Waschki in providing background for this study. He reported that many groups are looking at this as a marker of risk in a variety of chronic diseases.
In fact, a group working independently published a study in COPD just weeks before the ERS Congress that was complementary to those presented by Dr. Waschki. In this study, the goal was to evaluate troponin I as a predictor of cardiovascular events and cardiovascular death (Adamson PD et al. J Am Coll Cardiol 2018;72:1126-37). Performed as a subgroup analysis of 1,599 COPD patients participating in a large treatment trial, there was an almost fourfold increase in the risk of cardiovascular events (HR, 3.7; P = .012) when those in the highest quintile of troponin I (greater than 7.7 ng/ML) were compared with those in the lowest quintile (less than 2.3 ng/mL).
When compared for cardiovascular death, the highest quintile, relative to the lowest quintile, had a more than 20-fold increased risk of cardiovascular death (HR 20.1; P = .005). In the Adamson et al. study, which evaluated inhaled therapies for COPD, treatment response had no impact on troponin I levels or on the risk of cardiovascular events or death.
Based on this study and his own data, Dr. Waschki believes troponin I, which is readily ordered laboratory value, appears to be a useful tool for identifying COPD patients at high risk of death.
“The major message is that after adjusting for all known COPD and cardiovascular risk factors, troponin I remains a significant independent predictor of mortality,” he said.
Dr. Waschki reports no relevant conflicts of interest.
REPORTING FROM ERS CONGRESS 2018
Key clinical point: Elevated troponin I identifies COPD patients with increased mortality risk independent of all other clinical risk markers.
Major finding: With high troponin I levels, all-cause mortality was increased 69% after researchers adjusted for other risk markers.
Study details: Analysis drawn from on-going multicenter cohort study
Disclosures: Dr. Waschki reports no relevant conflicts of interest.
Guideline-recommended tests’ prognostic ability affirmed in prostanoid-treated PAH
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
The results of guideline-recommended prognostic tests that measure mortality risk in patients with pulmonary arterial hypertension (PAH) are strongly associated with survival in those who are receiving a parenteral prostanoid, according to a recent study.
Patients with no lower-risk findings or at least two higher-risk findings had the worst outcomes, reported lead author Sonja Bartolome, MD, of the University of Texas Southwestern Medical Center in Dallas, and her colleagues.
Prostanoids are the most effective therapy for advanced PAH. However, patients may respond inadequately, so guidelines recommend lung transplant evaluation 3 months after starting a prostanoid.
The current study relied upon the 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) consensus guidelines. The guidelines recommend several tests to determine adequate response to therapy, including invasive hemodynamic measures, brain natriuretic peptide (BNP) level, N-terminal BNP (NT-proBNP) level, 6-minute walk distance (6MWD), and functional class (FC). Results of these tests are sorted into three hazard ratios for mortality: lower, intermediate, or higher risk.
It is commonly accepted that these risk categories can predict survival. For example, a patient with several higher-risk results and no lower-risk results would have a poor prognosis. However, the reliability of this method is poorly studied.
“In practicality the definition of an ‘inadequate response’ remains nebulous given that data on prognostic markers in patients on advanced therapy is limited,” the authors wrote. Their report was published in Chest®. “We therefore sought to evaluate whether consensus guidelines recommended prognostic measures associate with survival free from transplant in PAH patients initiating parenteral prostanoids.”
The retrospective study involved 195 patients with group 1 PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016. Diagnosis relied upon CT angiography, ventilation-perfusion scan, pulmonary function testing, cardiac catheterization, or echocardiogram. Eligible diagnoses were idiopathic PAH (n = 111), heritable PAH (n = 9), and PAH associated with connective tissue disease (n = 61), congenital heart disease (n = 12), and HIV (n = 2).
Patients received either IV epoprostenol (n = 132), SC treprostinil (n = 38), or IV treprostinil (n = 25). Routine prognostic testing was done prior to prostanoid therapy, and again at least 90 days later (with right heart catheterization). The investigators then analyzed the data for associations between test outcomes and survival.
Results showed that survival rates at 1, 2, and 3 years were 84%, 77%, and 67%, respectively. All major prognostic measures improved after patients started a prostanoid. Better SVO2, BNP, NT-proBNP, 6MWD, and FC were associated with survival, but cardiac index (CI) was not. Survival was least likely in patients who had at least two higher-risk measures or no lower-risk measures; of these patients, less than 50% were alive after 2 years.
“These findings are likely broadly applicable to PAH patients being treated with parenteral prostanoids,” the authors wrote, citing the fact that all patients in the study were newly started on either of the two parenteral prostanoids currently available in the United States (including patients who were treatment naive as well as those transitioning to parenteral therapy) and the study involved patients with multiple PAH subtypes. They also noted that 97% of patients were receiving combination therapy at first follow-up, “reflecting the more frequent use of combinations of medications in the modern era.”
However, not all of the prognostic measures were reliable, particularly CI.
Although CI is used as a major determinant for lung transplant, the authors noted that the lack of association between CI and survival suggests that “the strength and usefulness of some individual prognostic measures may differ for prostanoid-treated PAH patients.”
Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050
FROM CHEST®
Key clinical point: Survival in patients with pulmonary arterial hypertension (PAH) who are receiving a parenteral prostanoid is closely associated with the results of most guideline-recommended prognostic tests that measure mortality risk.
Major finding:
Study details: A retrospective study of 195 patients with PAH at multiple treatment centers who received a parenteral prostanoid between 2007 and 2016.
Disclosures: Some of the authors disclosed financial ties to United Therapeutics, which markets treprostinil for infusion (Remodulin), and Actelion, which markets epoprostenol for injection (Veletri), as well as other pharmaceutical companies.
Source: Bartolome S et al. Chest. 2018 Sep 1. doi: 10.1016/j.chest.2018.03.050.
Most in-hospital pneumonia deaths may not be preventable
Most in-hospital deaths from community-acquired pneumonia are not preventable with current medical therapy, according to an analysis of deaths at five U.S. hospitals with expertise in pneumonia care.
Adults who are hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality but it is unclear whether an improvement in care could lower this risk, noted the study authors led by Grant W. Waterer, MBBS, PhD, of Northwestern University, Chicago.
“Understanding the circumstances in which CAP patients die could facilitate improvements in the management of CAP by enabling future improvement efforts to focus on common preventable causes of death,” they wrote. Their report was published in CHEST®.
They therefore performed a secondary analysis of the Etiology of Pneumonia in the Community (EPIC) study involving adults hospitalized with CAP between January 2010 and June 2012 across five tertiary-care hospitals in the United States.
The clinical characteristics of patients who died in the hospital were compared with those of patients who survived to hospital discharge. Chronic heart failure, chronic obstructive pulmonary disease, coronary artery disease, chronic liver disease, cerebrovascular disease, cancer (excluding skin cancer), and diabetes were considered as severe chronic comorbidities based on their association with increased mortality and ICU admission in CAP severity scores.
Deaths caused by septic shock, respiratory failure, multisystem organ failure, cardiopulmonary arrest prior to stabilization of CAP, and endocarditis, were considered to be directly related to CAP.
Conversely, causes of death indirectly related to CAP included acute cardiovascular disease, stroke, acute renal failure, and secondary infections developed after hospitalization. Deaths caused by cancer, cirrhosis, and chronic neurologic conditions were considered unrelated to CAP.
Medical notes were assessed to determine whether the patient received management consistent with current recommendations; for example, antibiotics consistent with guidelines from the Infectious Diseases Society of America.
End-of-life limitations in care, such as patient/family decision not to proceed with full medical treatment, also were considered by the research team.
Results showed that among the 2,320 patients with radiographically confirmed CAP, 52 died during initial hospitalization, 33 of whom were aged 65 years or older, and 32 of whom had two or more chronic comorbidities.
Most of the in-hospital deaths occurred early in the hospitalization: 35 within the first 10 days of admission, and 5 after 30 days in hospital.
CAP was judged by an expert physician review panel to be the direct cause of death in 27 of the patients, 10 with CAP having an indirect role with major contribution, 9 with CAP having an indirect role with minor contribution, and 6 with CAP having no role in death.
Do-not-resuscitate orders were present at the time of death for 21 of the patients.
Forty-five of the patients were admitted to an ICU, with 37 dying in the ICU. The eight patients who died on the ward after transfer out of the ICU had end-of-life limitations of care in place.
The researchers noted that the number of patients dying in the ICU was greater in the United States, possibly because in Europe fewer patients are admitted to an ICU.
“This discrepancy likely reflects cultural differences between the U.S. and Europe in the role of intensive care for patients with advanced age and/or advanced comorbid conditions,” they noted.
Overall, the physician review panel identified nine patients who had a lapse in quality of in-hospital CAP care, with four of the deaths potentially linked to this lapse in care.
However, two of the patients had end-of-life limitations of care in place, which according to the authors meant that “only two patients undergoing full medical treatment without end-of-life limitations of care had an identified lapse in quality of in-hospital pneumonia care potentially contributing to in-hospital death, including one with a delay in antibiotics for over an hour in the presence of shock and one with initial antibiotics not consistent with IDSA/ATS guidelines.”
The research team concluded that most in-hospital deaths among adult patients admitted with CAP in their study would not have been preventable with higher quality in-hospital pneumonia care.
“Many of the in-hospital deaths among patients admitted with CAP occurred in older patients with severe comorbidities and end-of-life limitations in care,” they noted.
They said the influence of end-of-life limitations on care short of full palliation was an important finding, with all patients who died outside the ICU having end-of-life limitations in care.
“Current diagnostic related group (DRG) and international classification of diseases (ICD) coding systems do not have the necessary nuances to capture these limitations of care, yet they are clearly important factors in determining whether patients experience in-hospital death,” they added.
Dr. Waterer reported no conflicts. Two coauthors reported potential conflicts of interest in relation to consulting fees from several pharmaceutical companies.
SOURCE: Waterer G. et al. CHEST 2018;154(3):628-35. doi: 10.1016/j.chest.2018.05.021.
Most in-hospital deaths from community-acquired pneumonia are not preventable with current medical therapy, according to an analysis of deaths at five U.S. hospitals with expertise in pneumonia care.
Adults who are hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality but it is unclear whether an improvement in care could lower this risk, noted the study authors led by Grant W. Waterer, MBBS, PhD, of Northwestern University, Chicago.
“Understanding the circumstances in which CAP patients die could facilitate improvements in the management of CAP by enabling future improvement efforts to focus on common preventable causes of death,” they wrote. Their report was published in CHEST®.
They therefore performed a secondary analysis of the Etiology of Pneumonia in the Community (EPIC) study involving adults hospitalized with CAP between January 2010 and June 2012 across five tertiary-care hospitals in the United States.
The clinical characteristics of patients who died in the hospital were compared with those of patients who survived to hospital discharge. Chronic heart failure, chronic obstructive pulmonary disease, coronary artery disease, chronic liver disease, cerebrovascular disease, cancer (excluding skin cancer), and diabetes were considered as severe chronic comorbidities based on their association with increased mortality and ICU admission in CAP severity scores.
Deaths caused by septic shock, respiratory failure, multisystem organ failure, cardiopulmonary arrest prior to stabilization of CAP, and endocarditis, were considered to be directly related to CAP.
Conversely, causes of death indirectly related to CAP included acute cardiovascular disease, stroke, acute renal failure, and secondary infections developed after hospitalization. Deaths caused by cancer, cirrhosis, and chronic neurologic conditions were considered unrelated to CAP.
Medical notes were assessed to determine whether the patient received management consistent with current recommendations; for example, antibiotics consistent with guidelines from the Infectious Diseases Society of America.
End-of-life limitations in care, such as patient/family decision not to proceed with full medical treatment, also were considered by the research team.
Results showed that among the 2,320 patients with radiographically confirmed CAP, 52 died during initial hospitalization, 33 of whom were aged 65 years or older, and 32 of whom had two or more chronic comorbidities.
Most of the in-hospital deaths occurred early in the hospitalization: 35 within the first 10 days of admission, and 5 after 30 days in hospital.
CAP was judged by an expert physician review panel to be the direct cause of death in 27 of the patients, 10 with CAP having an indirect role with major contribution, 9 with CAP having an indirect role with minor contribution, and 6 with CAP having no role in death.
Do-not-resuscitate orders were present at the time of death for 21 of the patients.
Forty-five of the patients were admitted to an ICU, with 37 dying in the ICU. The eight patients who died on the ward after transfer out of the ICU had end-of-life limitations of care in place.
The researchers noted that the number of patients dying in the ICU was greater in the United States, possibly because in Europe fewer patients are admitted to an ICU.
“This discrepancy likely reflects cultural differences between the U.S. and Europe in the role of intensive care for patients with advanced age and/or advanced comorbid conditions,” they noted.
Overall, the physician review panel identified nine patients who had a lapse in quality of in-hospital CAP care, with four of the deaths potentially linked to this lapse in care.
However, two of the patients had end-of-life limitations of care in place, which according to the authors meant that “only two patients undergoing full medical treatment without end-of-life limitations of care had an identified lapse in quality of in-hospital pneumonia care potentially contributing to in-hospital death, including one with a delay in antibiotics for over an hour in the presence of shock and one with initial antibiotics not consistent with IDSA/ATS guidelines.”
The research team concluded that most in-hospital deaths among adult patients admitted with CAP in their study would not have been preventable with higher quality in-hospital pneumonia care.
“Many of the in-hospital deaths among patients admitted with CAP occurred in older patients with severe comorbidities and end-of-life limitations in care,” they noted.
They said the influence of end-of-life limitations on care short of full palliation was an important finding, with all patients who died outside the ICU having end-of-life limitations in care.
“Current diagnostic related group (DRG) and international classification of diseases (ICD) coding systems do not have the necessary nuances to capture these limitations of care, yet they are clearly important factors in determining whether patients experience in-hospital death,” they added.
Dr. Waterer reported no conflicts. Two coauthors reported potential conflicts of interest in relation to consulting fees from several pharmaceutical companies.
SOURCE: Waterer G. et al. CHEST 2018;154(3):628-35. doi: 10.1016/j.chest.2018.05.021.
Most in-hospital deaths from community-acquired pneumonia are not preventable with current medical therapy, according to an analysis of deaths at five U.S. hospitals with expertise in pneumonia care.
Adults who are hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality but it is unclear whether an improvement in care could lower this risk, noted the study authors led by Grant W. Waterer, MBBS, PhD, of Northwestern University, Chicago.
“Understanding the circumstances in which CAP patients die could facilitate improvements in the management of CAP by enabling future improvement efforts to focus on common preventable causes of death,” they wrote. Their report was published in CHEST®.
They therefore performed a secondary analysis of the Etiology of Pneumonia in the Community (EPIC) study involving adults hospitalized with CAP between January 2010 and June 2012 across five tertiary-care hospitals in the United States.
The clinical characteristics of patients who died in the hospital were compared with those of patients who survived to hospital discharge. Chronic heart failure, chronic obstructive pulmonary disease, coronary artery disease, chronic liver disease, cerebrovascular disease, cancer (excluding skin cancer), and diabetes were considered as severe chronic comorbidities based on their association with increased mortality and ICU admission in CAP severity scores.
Deaths caused by septic shock, respiratory failure, multisystem organ failure, cardiopulmonary arrest prior to stabilization of CAP, and endocarditis, were considered to be directly related to CAP.
Conversely, causes of death indirectly related to CAP included acute cardiovascular disease, stroke, acute renal failure, and secondary infections developed after hospitalization. Deaths caused by cancer, cirrhosis, and chronic neurologic conditions were considered unrelated to CAP.
Medical notes were assessed to determine whether the patient received management consistent with current recommendations; for example, antibiotics consistent with guidelines from the Infectious Diseases Society of America.
End-of-life limitations in care, such as patient/family decision not to proceed with full medical treatment, also were considered by the research team.
Results showed that among the 2,320 patients with radiographically confirmed CAP, 52 died during initial hospitalization, 33 of whom were aged 65 years or older, and 32 of whom had two or more chronic comorbidities.
Most of the in-hospital deaths occurred early in the hospitalization: 35 within the first 10 days of admission, and 5 after 30 days in hospital.
CAP was judged by an expert physician review panel to be the direct cause of death in 27 of the patients, 10 with CAP having an indirect role with major contribution, 9 with CAP having an indirect role with minor contribution, and 6 with CAP having no role in death.
Do-not-resuscitate orders were present at the time of death for 21 of the patients.
Forty-five of the patients were admitted to an ICU, with 37 dying in the ICU. The eight patients who died on the ward after transfer out of the ICU had end-of-life limitations of care in place.
The researchers noted that the number of patients dying in the ICU was greater in the United States, possibly because in Europe fewer patients are admitted to an ICU.
“This discrepancy likely reflects cultural differences between the U.S. and Europe in the role of intensive care for patients with advanced age and/or advanced comorbid conditions,” they noted.
Overall, the physician review panel identified nine patients who had a lapse in quality of in-hospital CAP care, with four of the deaths potentially linked to this lapse in care.
However, two of the patients had end-of-life limitations of care in place, which according to the authors meant that “only two patients undergoing full medical treatment without end-of-life limitations of care had an identified lapse in quality of in-hospital pneumonia care potentially contributing to in-hospital death, including one with a delay in antibiotics for over an hour in the presence of shock and one with initial antibiotics not consistent with IDSA/ATS guidelines.”
The research team concluded that most in-hospital deaths among adult patients admitted with CAP in their study would not have been preventable with higher quality in-hospital pneumonia care.
“Many of the in-hospital deaths among patients admitted with CAP occurred in older patients with severe comorbidities and end-of-life limitations in care,” they noted.
They said the influence of end-of-life limitations on care short of full palliation was an important finding, with all patients who died outside the ICU having end-of-life limitations in care.
“Current diagnostic related group (DRG) and international classification of diseases (ICD) coding systems do not have the necessary nuances to capture these limitations of care, yet they are clearly important factors in determining whether patients experience in-hospital death,” they added.
Dr. Waterer reported no conflicts. Two coauthors reported potential conflicts of interest in relation to consulting fees from several pharmaceutical companies.
SOURCE: Waterer G. et al. CHEST 2018;154(3):628-35. doi: 10.1016/j.chest.2018.05.021.
FROM CHEST
Key clinical point: Most in-hospital deaths from community-acquired pneumonia are not preventable with current medical therapy.
Major finding: Two out of 52 patients who died in-hospital from community-acquired pneumonia (CAP) who were undergoing full medical treatment without end-of-life limitations of care had an identified lapse in quality of in-hospital pneumonia care that potentially contributed to their death.
Study details: A secondary analysis of the prospective multicenter Etiology of Pneumonia in the Community (EPIC) study involving 2,320 adults with radiographically confirmed CAP.
Disclosures: Dr. Waterer reported no conflicts. Two coauthors reported potential conflicts of interest in relation to consulting fees from several pharmaceutical companies.
Source: Waterer G. et al. CHEST 2018;154(3):628-35.
Short sleep linked to elevated blood pressure
CHICAGO – Consider 24-hour ambulatory blood pressure monitoring when patients complain about not getting enough sleep. You might catch hypertension early, according to researchers from the University of Pennsylvania, Philadelphia, and elsewhere.
They found a less than 7 hours a night and a mean in the study of 5.5 hours. Every 2-2.5 minutes of lost sleep was associated with an increase of 1 mm Hg in 24-hour mean systolic blood pressure and a increase of 1 beat per minute in heart rate.
The relationship was independent of office BP, nocturnal dipping status, and BP variability. It held in both the obese and nonobese, and in patients with and without obstructive sleep apnea (OSA). However, the relationship was found only among subjects who were not on antihypertensive medications.
“Adults with shorter sleep duration may benefit from screening with 24-hour ambulatory BP monitoring to promote earlier detection of hypertension and potentially mitigate the” the risk of cardiovascular disease. “This may be particularly important in screening for masked hypertension,” meaning normal pressures in the office, but elevated pressures at home, said investigators led by Jordana Cohen, MD, of the department of medicine at the University of Pennsylvania in a presentation at the joint scientific sessions of AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Dr. Cohen suggested that perhaps the sympathetic and endothelial derangements that drive hypertension in OSA also affect people with insufficient sleep. It may be that the normal morning surge in blood pressure persists longer into the day, she suggested. The investigative team analyzed data from two studies. The first, LIMBS (Lifestyle Modification in BP Lowering Study), was a phase 2 trial assessing yoga for blood pressure lowering. It was conducted in West Philadelphia and excluded people with diabetes, hypertension, OSA, and kidney or cardiovascular disease. The new analysis included 66 LIMBS subjects who had 24-hour blood pressure monitoring and kept sleep diaries to record their sleep duration (J Clin Hypertens (Greenwich). 2016 Aug;18[8]:809-16).
The team also analyzed 153 subjects from the PISA (Penn Icelandic Sleep Apnea) cohort, an ongoing project assessing continuous positive airway pressure for OSA, among other things. PISA includes patients with OSA, diabetes, hypertension, and kidney or cardiovascular disease. Sleep duration in the 153 subjects was again self-reported, but corroborated by actigraphy (J Sleep Res. 2015 Jun;24[3]:328-38).
The new findings were driven mostly by higher daytime systolic BP among short sleepers in LIMBS, and higher systolic pressures during both day and night among short sleepers in PISA, compared with subjects who slept at least 7 hours, and a mean of 8.5 hours, with napping included in overall sleep duration assessment.
In LIMBS, the mean 24-hour systolic BP was 12.7 mm Hg higher and the average heart rate 8 bpm faster among short sleepers; in PISA, the mean 24-hour systolic BP was 4.7 mm Hg higher and the heart rate 2 bpm faster.
Every 2.57 minutes of sleep lost in LIMBS and every 1.99 minute of lost sleep in PISA was associated with a 1–mm Hg gain in mean systolic BP and about a 1-bpm increase in heart rate. The findings were statistically significant and adjusted for age, race, body mass index, nocturnal dipping status, and office systolic blood pressure.
Baseline characteristics were generally well matched between short and long sleepers in both studies. However, while mean office systolic BP in LIMBS was the same in both sleep groups at about 139 mm Hg, the mean office systolic BP among long sleepers in PISA was 130 mm Hg versus 136 mm Hg among short sleepers, a significant difference.
It’s unclear why some people slept less, Dr. Cohen said, and the use of sleeping pills wasn’t considered in the analysis. Patients were an average of about 50 years old, with a body mass index of about 30 mg/m2. The same model of 24-hour blood pressure monitor was used in both studies.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
CHICAGO – Consider 24-hour ambulatory blood pressure monitoring when patients complain about not getting enough sleep. You might catch hypertension early, according to researchers from the University of Pennsylvania, Philadelphia, and elsewhere.
They found a less than 7 hours a night and a mean in the study of 5.5 hours. Every 2-2.5 minutes of lost sleep was associated with an increase of 1 mm Hg in 24-hour mean systolic blood pressure and a increase of 1 beat per minute in heart rate.
The relationship was independent of office BP, nocturnal dipping status, and BP variability. It held in both the obese and nonobese, and in patients with and without obstructive sleep apnea (OSA). However, the relationship was found only among subjects who were not on antihypertensive medications.
“Adults with shorter sleep duration may benefit from screening with 24-hour ambulatory BP monitoring to promote earlier detection of hypertension and potentially mitigate the” the risk of cardiovascular disease. “This may be particularly important in screening for masked hypertension,” meaning normal pressures in the office, but elevated pressures at home, said investigators led by Jordana Cohen, MD, of the department of medicine at the University of Pennsylvania in a presentation at the joint scientific sessions of AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Dr. Cohen suggested that perhaps the sympathetic and endothelial derangements that drive hypertension in OSA also affect people with insufficient sleep. It may be that the normal morning surge in blood pressure persists longer into the day, she suggested. The investigative team analyzed data from two studies. The first, LIMBS (Lifestyle Modification in BP Lowering Study), was a phase 2 trial assessing yoga for blood pressure lowering. It was conducted in West Philadelphia and excluded people with diabetes, hypertension, OSA, and kidney or cardiovascular disease. The new analysis included 66 LIMBS subjects who had 24-hour blood pressure monitoring and kept sleep diaries to record their sleep duration (J Clin Hypertens (Greenwich). 2016 Aug;18[8]:809-16).
The team also analyzed 153 subjects from the PISA (Penn Icelandic Sleep Apnea) cohort, an ongoing project assessing continuous positive airway pressure for OSA, among other things. PISA includes patients with OSA, diabetes, hypertension, and kidney or cardiovascular disease. Sleep duration in the 153 subjects was again self-reported, but corroborated by actigraphy (J Sleep Res. 2015 Jun;24[3]:328-38).
The new findings were driven mostly by higher daytime systolic BP among short sleepers in LIMBS, and higher systolic pressures during both day and night among short sleepers in PISA, compared with subjects who slept at least 7 hours, and a mean of 8.5 hours, with napping included in overall sleep duration assessment.
In LIMBS, the mean 24-hour systolic BP was 12.7 mm Hg higher and the average heart rate 8 bpm faster among short sleepers; in PISA, the mean 24-hour systolic BP was 4.7 mm Hg higher and the heart rate 2 bpm faster.
Every 2.57 minutes of sleep lost in LIMBS and every 1.99 minute of lost sleep in PISA was associated with a 1–mm Hg gain in mean systolic BP and about a 1-bpm increase in heart rate. The findings were statistically significant and adjusted for age, race, body mass index, nocturnal dipping status, and office systolic blood pressure.
Baseline characteristics were generally well matched between short and long sleepers in both studies. However, while mean office systolic BP in LIMBS was the same in both sleep groups at about 139 mm Hg, the mean office systolic BP among long sleepers in PISA was 130 mm Hg versus 136 mm Hg among short sleepers, a significant difference.
It’s unclear why some people slept less, Dr. Cohen said, and the use of sleeping pills wasn’t considered in the analysis. Patients were an average of about 50 years old, with a body mass index of about 30 mg/m2. The same model of 24-hour blood pressure monitor was used in both studies.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
CHICAGO – Consider 24-hour ambulatory blood pressure monitoring when patients complain about not getting enough sleep. You might catch hypertension early, according to researchers from the University of Pennsylvania, Philadelphia, and elsewhere.
They found a less than 7 hours a night and a mean in the study of 5.5 hours. Every 2-2.5 minutes of lost sleep was associated with an increase of 1 mm Hg in 24-hour mean systolic blood pressure and a increase of 1 beat per minute in heart rate.
The relationship was independent of office BP, nocturnal dipping status, and BP variability. It held in both the obese and nonobese, and in patients with and without obstructive sleep apnea (OSA). However, the relationship was found only among subjects who were not on antihypertensive medications.
“Adults with shorter sleep duration may benefit from screening with 24-hour ambulatory BP monitoring to promote earlier detection of hypertension and potentially mitigate the” the risk of cardiovascular disease. “This may be particularly important in screening for masked hypertension,” meaning normal pressures in the office, but elevated pressures at home, said investigators led by Jordana Cohen, MD, of the department of medicine at the University of Pennsylvania in a presentation at the joint scientific sessions of AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Dr. Cohen suggested that perhaps the sympathetic and endothelial derangements that drive hypertension in OSA also affect people with insufficient sleep. It may be that the normal morning surge in blood pressure persists longer into the day, she suggested. The investigative team analyzed data from two studies. The first, LIMBS (Lifestyle Modification in BP Lowering Study), was a phase 2 trial assessing yoga for blood pressure lowering. It was conducted in West Philadelphia and excluded people with diabetes, hypertension, OSA, and kidney or cardiovascular disease. The new analysis included 66 LIMBS subjects who had 24-hour blood pressure monitoring and kept sleep diaries to record their sleep duration (J Clin Hypertens (Greenwich). 2016 Aug;18[8]:809-16).
The team also analyzed 153 subjects from the PISA (Penn Icelandic Sleep Apnea) cohort, an ongoing project assessing continuous positive airway pressure for OSA, among other things. PISA includes patients with OSA, diabetes, hypertension, and kidney or cardiovascular disease. Sleep duration in the 153 subjects was again self-reported, but corroborated by actigraphy (J Sleep Res. 2015 Jun;24[3]:328-38).
The new findings were driven mostly by higher daytime systolic BP among short sleepers in LIMBS, and higher systolic pressures during both day and night among short sleepers in PISA, compared with subjects who slept at least 7 hours, and a mean of 8.5 hours, with napping included in overall sleep duration assessment.
In LIMBS, the mean 24-hour systolic BP was 12.7 mm Hg higher and the average heart rate 8 bpm faster among short sleepers; in PISA, the mean 24-hour systolic BP was 4.7 mm Hg higher and the heart rate 2 bpm faster.
Every 2.57 minutes of sleep lost in LIMBS and every 1.99 minute of lost sleep in PISA was associated with a 1–mm Hg gain in mean systolic BP and about a 1-bpm increase in heart rate. The findings were statistically significant and adjusted for age, race, body mass index, nocturnal dipping status, and office systolic blood pressure.
Baseline characteristics were generally well matched between short and long sleepers in both studies. However, while mean office systolic BP in LIMBS was the same in both sleep groups at about 139 mm Hg, the mean office systolic BP among long sleepers in PISA was 130 mm Hg versus 136 mm Hg among short sleepers, a significant difference.
It’s unclear why some people slept less, Dr. Cohen said, and the use of sleeping pills wasn’t considered in the analysis. Patients were an average of about 50 years old, with a body mass index of about 30 mg/m2. The same model of 24-hour blood pressure monitor was used in both studies.
The work was funded by the National Institutes of Health. The investigators had no disclosures.
REPORTING FROM JOINT HYPERTENSION 2018
Key clinical point: Ambulatory blood pressure monitoring in patients complaining about lack of sleep could detect hypertension.
Major finding: Every 2-2.5 minutes of lost sleep was associated with a 1–mm Hg increase in 24-hour mean systolic blood pressure and a 1-bpm increase in heart rate.
Study details: Post-hoc review of 219 patients in two trials
Disclosures: The work was funded by the National Institutes of Health. The investigators didn’t have any disclosures.
Text Messaging Streamlines Appointment Process
Millions of VA health care appointments are missed each year. But VEText aims to change that by sending reminders to veterans via their cell phones.
Five months after the automated interactive text-message system was introduced, > 3 million patients have received reminder texts—and have then canceled 319,504 appointments, freeing up time slots for other veterans to use.
More than 100 VA facilities are using VEText. Veterans who have used the health care system and have a cell phone number listed in their electronic health records (EHR) are automatically enrolled in VEText. The first text message reminder is sent 7 days before the appointment, and a second reminder is sent 2 days before the appointment. (The timing and frequency may vary by facility.) Veterans with multiple appointments on the same day receive multiple remainders. Veterans can also opt out of the text-messaging reminders.
Because it is integrated with the VA’s EHR system, VEText does not require manual action by VA staff, which can mean staff have more time to provide more personalized care, the VA says.
For more information about VEText, visit https://www.va.gov/HEALTH/VEText.asp.
Millions of VA health care appointments are missed each year. But VEText aims to change that by sending reminders to veterans via their cell phones.
Five months after the automated interactive text-message system was introduced, > 3 million patients have received reminder texts—and have then canceled 319,504 appointments, freeing up time slots for other veterans to use.
More than 100 VA facilities are using VEText. Veterans who have used the health care system and have a cell phone number listed in their electronic health records (EHR) are automatically enrolled in VEText. The first text message reminder is sent 7 days before the appointment, and a second reminder is sent 2 days before the appointment. (The timing and frequency may vary by facility.) Veterans with multiple appointments on the same day receive multiple remainders. Veterans can also opt out of the text-messaging reminders.
Because it is integrated with the VA’s EHR system, VEText does not require manual action by VA staff, which can mean staff have more time to provide more personalized care, the VA says.
For more information about VEText, visit https://www.va.gov/HEALTH/VEText.asp.
Millions of VA health care appointments are missed each year. But VEText aims to change that by sending reminders to veterans via their cell phones.
Five months after the automated interactive text-message system was introduced, > 3 million patients have received reminder texts—and have then canceled 319,504 appointments, freeing up time slots for other veterans to use.
More than 100 VA facilities are using VEText. Veterans who have used the health care system and have a cell phone number listed in their electronic health records (EHR) are automatically enrolled in VEText. The first text message reminder is sent 7 days before the appointment, and a second reminder is sent 2 days before the appointment. (The timing and frequency may vary by facility.) Veterans with multiple appointments on the same day receive multiple remainders. Veterans can also opt out of the text-messaging reminders.
Because it is integrated with the VA’s EHR system, VEText does not require manual action by VA staff, which can mean staff have more time to provide more personalized care, the VA says.
For more information about VEText, visit https://www.va.gov/HEALTH/VEText.asp.
UN aims to eradicate TB by 2030
A concerted a lethal disease affecting one-quarter of the world’s population by the year 2030.
On September 26 the United Nations General Assembly will convene a high-level meeting of global stakeholders to solidify the eradication plan, addressing the global crisis of tuberculosis (TB), the world’s most deadly infectious disease.
“We must seize the moment,” said Tereza Kasaeva, MD, director of the World Health Organization’s global TB program, speaking at a telebriefing and press conference accompanying the release of the World Health Organization’s annual global tuberculosis report. “It’s unacceptable in the 21st century that millions lose their lives to this preventable and curable disease.”
TB caused 1.6 million deaths globally in 2017, and the World Health Organization (WHO) estimates that of the 10 million new cases of TB last year, 558,000 are multi-drug resistant (MDR) infections.
Though death rates and new cases are falling globally each year, significantly more resources are needed to boost access to preventive treatment for latent TB infection; “Most people needing it are not yet accessing care,” according to the press briefing accompanying the report.
A review and commentary on TB incubation and latency published in BMJ (2018;362:k2738 doi: 10.1136/bmj.k2738; e-pub 23 Aug 2018) has called into question the focus preventive treatment of latent cases at the expense of reaching those most likely to die from TB (e.g., HIV patients, children of individuals living with active TB). The authors state that “latent” TB is identified by indirect evidence of present or past infection with Mycobacterium tuberculosis as inferred by a detectable adaptive immune response to M tuberculosis antigens. Active TB infection is overwhelmingly the result of a primary infection and almost always occurs within two years.
In order to meet the ambitious goal of TB eradication by the year 2030, treatment coverage must rise to 90% globally from the current 64%, according to the report.
Progress in southern Africa and in the Russian Federation, where efforts have led to a 30% reduction in TB mortality and a decrease in incidence of 5% per year, show that steep reductions in TB are possible when resources are brought to bear on the problem, said Dr. Kasaeva. “We should acknowledge that actions in some countries and regions show that progress can accelerate,” she said. Still, she noted, “Four thousand lives per day are lost to TB. Tuberculosis is the leading killer of people living with HIV, and the major cause of deaths related to antimicrobial resistance” at a global level.
Two thirds of all TB cases occur in eight countries, with India, China, and Indonesia leading this group. About half of the cases of MDR TB occur in India, China, and Russia, said Dr. Kasaeva, and globally only one in four individuals with MDR TB who need access to treatment have received it. “We need to urgently tackle the multidrug resistant TB public health crisis,” she said.
Major impediments to successful public health efforts against TB are underdiagnosis and underreporting: It is estimated that 3.6 million of 2017’s 10 million new cases were not officially recorded or reported. Countries where these problems are most serious include India, Indonesia, and Nigeria. Fewer than half of the children with TB are reported globally, according to the report.
People living with HIV/AIDS who are also infected with TB number nearly 1,000,000, but only about half of these were officially reported in 2017.
In terms of prevention priorities, WHO has recommended targeting treatment of latent TB in two groups: People living with HIV/AIDS, and children under the age of 5 years who live in households with TB-infected individuals.
“To enable these actions,” said Dr. Kasaeva, “we need strengthened commitments not just for TB care, but for overall health services. So the aim for universal coverage is real.” Underreporting is particularly prevalent in lower income countries with large unregulated private sectors, she said, though India and Indonesia have taken corrective steps to increase reporting.
A meaningful global initiative will not come cheap: The current annual shortfall in funding for TB prevention, diagnosis, and treatment is about $3.5 billion. By the year 2022, the gap between funding and what’s needed to stay on track for the 2030 target will be over $6 billion, said Dr. Kasaeva.
The best use of increased resources for TB eradication will be in locally focused efforts, said Irene Koek, MD, the United States Agency for International Development’s deputy administrator for global health. “It is likely that each region requires a tailored response.” Further, “to improve quality of care we need to ensure that services are patient centered,” she said at the press conference.
To that end, Dr. Koek expects that at the upcoming high-level meeting, the United Nations member states will be called on to develop an open framework, with clear accountability for monitoring and reviewing progress. The road forward should “celebrate accomplishments and acknowledge shortcomings,” she said. Some recent studies have shown that treatment success rates above 80% for patients with MDR TB can be achieved.
“Lessons learned from these experiences should be documented and shared in order to replicate success globally,” said Dr. Koek.
The United States, said Dr. Koek, is the leading global investor in TB research and treatment. “We welcome increased partnerships, especially with countries with the highest burden, to end global suffering from this disease.”
Eric Goosby, MD, the United Nations special envoy on TB, used his speaking time to lend some perspective to the social framework around TB’s longtime lethality.
There are aspects of TB infection that differentiate it from HIV/AIDS, said Dr. Goosby, who has spent most of his clinical and public health career on HIV/AIDS treatment and prevention. In contrast to an infection that at present requires a lifetime of treatment, TB can ordinarily be treated in 6 months, making it an unpleasant episode that an individual may be eager to move past. Additionally, the fact that TB has had a “hold on the world since the time of the ancient Egyptians” may paradoxically have served to lessen urgency in research and treatment efforts, he noted.
Dr. Goosby also spoke of the stigma surrounding TB, whose sufferers are likely to be facing dire poverty, malnutrition, and other infectious disease burdens. Civil society concerned with TB, he said, has spoken up “for those without a voice, for those who have difficulty advocating for themselves.”
Dr. Kasaeva agreed, noting that TB “affects the poorest of the poor, which makes it extraordinarily difficult for activism to come from that population.”
However, others have spoken for those affected, said Dr. Goosby. “The TB civil society has put its heart and soul this last year into gathering political will from leaders around the world…. It’s not a passive effort; it involves a lot of work.” During the past year of concerted effort, he said, “All of us have known the difficulty of pushing a political leader up that learning curve.”
As the upcoming high-level meeting approaches, those who have been working on the effort can feel the momentum, said Dr. Goosby. Still, he noted, “While there’s a significant step forward, this is not the time for a victory dance. This is really the time for a reflection...Do we understand the burden in our respective countries, and has the response been adequate?”
The goal for the meeting is to have leaders “step up to commit, not for one day, or for one meeting, but for the duration of the effort,” said Dr. Goosby. “We must make sure that the words that we hear next week from our leaders translate into action...Next week the world will say, ‘No more. No longer. No one is immune to TB. Tuberculosis is preventable; tuberculosis is treatable; tuberculosis is curable.’”
The BMJ commentary, by Marcel A. Behr, MD, of McGill International TB Centre, Infectious Diseases and Immunity in Global Health Program, McGill University Health Centre Research Institute, and his colleagues, recommend caution when building a prevention strategy around treating many millions of individuals with “latent” TB. They wrote, “Immunoreactivity to TB does not necessarily indicate the presence of live bacteria, as reactivity can persist after infection has been cleared. Classifying two billion people with evidence of immunoreactivity as having latent TB infection may divert fundamental research and public health interventions away from transmissible active TB disease and newly infected people at highest risk of progression to disease.”
This story was updated on 09/24/2018
A concerted a lethal disease affecting one-quarter of the world’s population by the year 2030.
On September 26 the United Nations General Assembly will convene a high-level meeting of global stakeholders to solidify the eradication plan, addressing the global crisis of tuberculosis (TB), the world’s most deadly infectious disease.
“We must seize the moment,” said Tereza Kasaeva, MD, director of the World Health Organization’s global TB program, speaking at a telebriefing and press conference accompanying the release of the World Health Organization’s annual global tuberculosis report. “It’s unacceptable in the 21st century that millions lose their lives to this preventable and curable disease.”
TB caused 1.6 million deaths globally in 2017, and the World Health Organization (WHO) estimates that of the 10 million new cases of TB last year, 558,000 are multi-drug resistant (MDR) infections.
Though death rates and new cases are falling globally each year, significantly more resources are needed to boost access to preventive treatment for latent TB infection; “Most people needing it are not yet accessing care,” according to the press briefing accompanying the report.
A review and commentary on TB incubation and latency published in BMJ (2018;362:k2738 doi: 10.1136/bmj.k2738; e-pub 23 Aug 2018) has called into question the focus preventive treatment of latent cases at the expense of reaching those most likely to die from TB (e.g., HIV patients, children of individuals living with active TB). The authors state that “latent” TB is identified by indirect evidence of present or past infection with Mycobacterium tuberculosis as inferred by a detectable adaptive immune response to M tuberculosis antigens. Active TB infection is overwhelmingly the result of a primary infection and almost always occurs within two years.
In order to meet the ambitious goal of TB eradication by the year 2030, treatment coverage must rise to 90% globally from the current 64%, according to the report.
Progress in southern Africa and in the Russian Federation, where efforts have led to a 30% reduction in TB mortality and a decrease in incidence of 5% per year, show that steep reductions in TB are possible when resources are brought to bear on the problem, said Dr. Kasaeva. “We should acknowledge that actions in some countries and regions show that progress can accelerate,” she said. Still, she noted, “Four thousand lives per day are lost to TB. Tuberculosis is the leading killer of people living with HIV, and the major cause of deaths related to antimicrobial resistance” at a global level.
Two thirds of all TB cases occur in eight countries, with India, China, and Indonesia leading this group. About half of the cases of MDR TB occur in India, China, and Russia, said Dr. Kasaeva, and globally only one in four individuals with MDR TB who need access to treatment have received it. “We need to urgently tackle the multidrug resistant TB public health crisis,” she said.
Major impediments to successful public health efforts against TB are underdiagnosis and underreporting: It is estimated that 3.6 million of 2017’s 10 million new cases were not officially recorded or reported. Countries where these problems are most serious include India, Indonesia, and Nigeria. Fewer than half of the children with TB are reported globally, according to the report.
People living with HIV/AIDS who are also infected with TB number nearly 1,000,000, but only about half of these were officially reported in 2017.
In terms of prevention priorities, WHO has recommended targeting treatment of latent TB in two groups: People living with HIV/AIDS, and children under the age of 5 years who live in households with TB-infected individuals.
“To enable these actions,” said Dr. Kasaeva, “we need strengthened commitments not just for TB care, but for overall health services. So the aim for universal coverage is real.” Underreporting is particularly prevalent in lower income countries with large unregulated private sectors, she said, though India and Indonesia have taken corrective steps to increase reporting.
A meaningful global initiative will not come cheap: The current annual shortfall in funding for TB prevention, diagnosis, and treatment is about $3.5 billion. By the year 2022, the gap between funding and what’s needed to stay on track for the 2030 target will be over $6 billion, said Dr. Kasaeva.
The best use of increased resources for TB eradication will be in locally focused efforts, said Irene Koek, MD, the United States Agency for International Development’s deputy administrator for global health. “It is likely that each region requires a tailored response.” Further, “to improve quality of care we need to ensure that services are patient centered,” she said at the press conference.
To that end, Dr. Koek expects that at the upcoming high-level meeting, the United Nations member states will be called on to develop an open framework, with clear accountability for monitoring and reviewing progress. The road forward should “celebrate accomplishments and acknowledge shortcomings,” she said. Some recent studies have shown that treatment success rates above 80% for patients with MDR TB can be achieved.
“Lessons learned from these experiences should be documented and shared in order to replicate success globally,” said Dr. Koek.
The United States, said Dr. Koek, is the leading global investor in TB research and treatment. “We welcome increased partnerships, especially with countries with the highest burden, to end global suffering from this disease.”
Eric Goosby, MD, the United Nations special envoy on TB, used his speaking time to lend some perspective to the social framework around TB’s longtime lethality.
There are aspects of TB infection that differentiate it from HIV/AIDS, said Dr. Goosby, who has spent most of his clinical and public health career on HIV/AIDS treatment and prevention. In contrast to an infection that at present requires a lifetime of treatment, TB can ordinarily be treated in 6 months, making it an unpleasant episode that an individual may be eager to move past. Additionally, the fact that TB has had a “hold on the world since the time of the ancient Egyptians” may paradoxically have served to lessen urgency in research and treatment efforts, he noted.
Dr. Goosby also spoke of the stigma surrounding TB, whose sufferers are likely to be facing dire poverty, malnutrition, and other infectious disease burdens. Civil society concerned with TB, he said, has spoken up “for those without a voice, for those who have difficulty advocating for themselves.”
Dr. Kasaeva agreed, noting that TB “affects the poorest of the poor, which makes it extraordinarily difficult for activism to come from that population.”
However, others have spoken for those affected, said Dr. Goosby. “The TB civil society has put its heart and soul this last year into gathering political will from leaders around the world…. It’s not a passive effort; it involves a lot of work.” During the past year of concerted effort, he said, “All of us have known the difficulty of pushing a political leader up that learning curve.”
As the upcoming high-level meeting approaches, those who have been working on the effort can feel the momentum, said Dr. Goosby. Still, he noted, “While there’s a significant step forward, this is not the time for a victory dance. This is really the time for a reflection...Do we understand the burden in our respective countries, and has the response been adequate?”
The goal for the meeting is to have leaders “step up to commit, not for one day, or for one meeting, but for the duration of the effort,” said Dr. Goosby. “We must make sure that the words that we hear next week from our leaders translate into action...Next week the world will say, ‘No more. No longer. No one is immune to TB. Tuberculosis is preventable; tuberculosis is treatable; tuberculosis is curable.’”
The BMJ commentary, by Marcel A. Behr, MD, of McGill International TB Centre, Infectious Diseases and Immunity in Global Health Program, McGill University Health Centre Research Institute, and his colleagues, recommend caution when building a prevention strategy around treating many millions of individuals with “latent” TB. They wrote, “Immunoreactivity to TB does not necessarily indicate the presence of live bacteria, as reactivity can persist after infection has been cleared. Classifying two billion people with evidence of immunoreactivity as having latent TB infection may divert fundamental research and public health interventions away from transmissible active TB disease and newly infected people at highest risk of progression to disease.”
This story was updated on 09/24/2018
A concerted a lethal disease affecting one-quarter of the world’s population by the year 2030.
On September 26 the United Nations General Assembly will convene a high-level meeting of global stakeholders to solidify the eradication plan, addressing the global crisis of tuberculosis (TB), the world’s most deadly infectious disease.
“We must seize the moment,” said Tereza Kasaeva, MD, director of the World Health Organization’s global TB program, speaking at a telebriefing and press conference accompanying the release of the World Health Organization’s annual global tuberculosis report. “It’s unacceptable in the 21st century that millions lose their lives to this preventable and curable disease.”
TB caused 1.6 million deaths globally in 2017, and the World Health Organization (WHO) estimates that of the 10 million new cases of TB last year, 558,000 are multi-drug resistant (MDR) infections.
Though death rates and new cases are falling globally each year, significantly more resources are needed to boost access to preventive treatment for latent TB infection; “Most people needing it are not yet accessing care,” according to the press briefing accompanying the report.
A review and commentary on TB incubation and latency published in BMJ (2018;362:k2738 doi: 10.1136/bmj.k2738; e-pub 23 Aug 2018) has called into question the focus preventive treatment of latent cases at the expense of reaching those most likely to die from TB (e.g., HIV patients, children of individuals living with active TB). The authors state that “latent” TB is identified by indirect evidence of present or past infection with Mycobacterium tuberculosis as inferred by a detectable adaptive immune response to M tuberculosis antigens. Active TB infection is overwhelmingly the result of a primary infection and almost always occurs within two years.
In order to meet the ambitious goal of TB eradication by the year 2030, treatment coverage must rise to 90% globally from the current 64%, according to the report.
Progress in southern Africa and in the Russian Federation, where efforts have led to a 30% reduction in TB mortality and a decrease in incidence of 5% per year, show that steep reductions in TB are possible when resources are brought to bear on the problem, said Dr. Kasaeva. “We should acknowledge that actions in some countries and regions show that progress can accelerate,” she said. Still, she noted, “Four thousand lives per day are lost to TB. Tuberculosis is the leading killer of people living with HIV, and the major cause of deaths related to antimicrobial resistance” at a global level.
Two thirds of all TB cases occur in eight countries, with India, China, and Indonesia leading this group. About half of the cases of MDR TB occur in India, China, and Russia, said Dr. Kasaeva, and globally only one in four individuals with MDR TB who need access to treatment have received it. “We need to urgently tackle the multidrug resistant TB public health crisis,” she said.
Major impediments to successful public health efforts against TB are underdiagnosis and underreporting: It is estimated that 3.6 million of 2017’s 10 million new cases were not officially recorded or reported. Countries where these problems are most serious include India, Indonesia, and Nigeria. Fewer than half of the children with TB are reported globally, according to the report.
People living with HIV/AIDS who are also infected with TB number nearly 1,000,000, but only about half of these were officially reported in 2017.
In terms of prevention priorities, WHO has recommended targeting treatment of latent TB in two groups: People living with HIV/AIDS, and children under the age of 5 years who live in households with TB-infected individuals.
“To enable these actions,” said Dr. Kasaeva, “we need strengthened commitments not just for TB care, but for overall health services. So the aim for universal coverage is real.” Underreporting is particularly prevalent in lower income countries with large unregulated private sectors, she said, though India and Indonesia have taken corrective steps to increase reporting.
A meaningful global initiative will not come cheap: The current annual shortfall in funding for TB prevention, diagnosis, and treatment is about $3.5 billion. By the year 2022, the gap between funding and what’s needed to stay on track for the 2030 target will be over $6 billion, said Dr. Kasaeva.
The best use of increased resources for TB eradication will be in locally focused efforts, said Irene Koek, MD, the United States Agency for International Development’s deputy administrator for global health. “It is likely that each region requires a tailored response.” Further, “to improve quality of care we need to ensure that services are patient centered,” she said at the press conference.
To that end, Dr. Koek expects that at the upcoming high-level meeting, the United Nations member states will be called on to develop an open framework, with clear accountability for monitoring and reviewing progress. The road forward should “celebrate accomplishments and acknowledge shortcomings,” she said. Some recent studies have shown that treatment success rates above 80% for patients with MDR TB can be achieved.
“Lessons learned from these experiences should be documented and shared in order to replicate success globally,” said Dr. Koek.
The United States, said Dr. Koek, is the leading global investor in TB research and treatment. “We welcome increased partnerships, especially with countries with the highest burden, to end global suffering from this disease.”
Eric Goosby, MD, the United Nations special envoy on TB, used his speaking time to lend some perspective to the social framework around TB’s longtime lethality.
There are aspects of TB infection that differentiate it from HIV/AIDS, said Dr. Goosby, who has spent most of his clinical and public health career on HIV/AIDS treatment and prevention. In contrast to an infection that at present requires a lifetime of treatment, TB can ordinarily be treated in 6 months, making it an unpleasant episode that an individual may be eager to move past. Additionally, the fact that TB has had a “hold on the world since the time of the ancient Egyptians” may paradoxically have served to lessen urgency in research and treatment efforts, he noted.
Dr. Goosby also spoke of the stigma surrounding TB, whose sufferers are likely to be facing dire poverty, malnutrition, and other infectious disease burdens. Civil society concerned with TB, he said, has spoken up “for those without a voice, for those who have difficulty advocating for themselves.”
Dr. Kasaeva agreed, noting that TB “affects the poorest of the poor, which makes it extraordinarily difficult for activism to come from that population.”
However, others have spoken for those affected, said Dr. Goosby. “The TB civil society has put its heart and soul this last year into gathering political will from leaders around the world…. It’s not a passive effort; it involves a lot of work.” During the past year of concerted effort, he said, “All of us have known the difficulty of pushing a political leader up that learning curve.”
As the upcoming high-level meeting approaches, those who have been working on the effort can feel the momentum, said Dr. Goosby. Still, he noted, “While there’s a significant step forward, this is not the time for a victory dance. This is really the time for a reflection...Do we understand the burden in our respective countries, and has the response been adequate?”
The goal for the meeting is to have leaders “step up to commit, not for one day, or for one meeting, but for the duration of the effort,” said Dr. Goosby. “We must make sure that the words that we hear next week from our leaders translate into action...Next week the world will say, ‘No more. No longer. No one is immune to TB. Tuberculosis is preventable; tuberculosis is treatable; tuberculosis is curable.’”
The BMJ commentary, by Marcel A. Behr, MD, of McGill International TB Centre, Infectious Diseases and Immunity in Global Health Program, McGill University Health Centre Research Institute, and his colleagues, recommend caution when building a prevention strategy around treating many millions of individuals with “latent” TB. They wrote, “Immunoreactivity to TB does not necessarily indicate the presence of live bacteria, as reactivity can persist after infection has been cleared. Classifying two billion people with evidence of immunoreactivity as having latent TB infection may divert fundamental research and public health interventions away from transmissible active TB disease and newly infected people at highest risk of progression to disease.”
This story was updated on 09/24/2018
FROM A WORLD HEALTH ORGANIZATION PRESS CONFERENCE
Best practices defined for proton therapy in mediastinal lymphomas
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
Proton therapy can help mitigate toxicity in adults with mediastinal lymphomas, but only when this modality offers a clear advantage over intensity-modulated radiotherapy, according to new guidelines from the International Lymphoma Radiation Oncology Group.
Proton therapy reduces radiation dose to organs at risk in certain clinical presentations, such as when the mediastinal target is on both sides of the heart. The advantages are not always clear in other situations, such as when the target spans the right side of the heart, or when the target is above the heart with no axillary involvement, according to guideline authors Bouthaina Dabaja, MD, professor and section chief of hematology in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, Houston, and her colleagues.
“The limited availability of proton therapy calls for case selection based on a clear understanding of which cases will derive most benefit from proton therapy as compared to advanced photon techniques,” Dr. Dabaja and her coauthors said in the guidelines, which were published in the journal Blood (doi: 10.1182/blood-2018-03-837633).
Along with intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy, proton therapy presents “another opportunity” for more conformal dose distribution and better sparing of organs at risk, according to the consensus recommendations. Proton therapy can greatly benefit certain patients with mediastinal disease. These include young female patients to reduce breast dose and risk of a secondary breast cancer, patients at high risk of radiation-related toxicity due to previous treatment, and patients with disease spanning below the origin of the left main stem coronary artery that is anterior to, posterior to, or on the left side of the heart.
“The relation of disease to organs at risk determines the situations in which proton therapy is most beneficial,” the experts said in the guidelines. However, the consideration of proton therapy needs to factor the complexities of proton therapy planning, the need to manage uncertainties, and the “evolving nature of the technology,” which includes the development of pencil beam scanning.
While passive scattering proton therapy (PSPT) is the least complex delivery technique, it is challenging because beams can conform only to one side of the target; by contrast, the experts said, active mode pencil beam scanning proton therapy (PBSPT) potentially provides better conformity and sparing of organs at risk.
“Because treatment involves delivery of individual controlled spots, inhomogenous doses can be created deliberately,” the guideline authors said in their report.
However, motion management is “of prime importance” with PBSPT, which is more sensitive to density changes in the beam path as compared to PSPT, they added. Toward that end, physicians should pay close attention to evaluating intrafractional movement, which is frequently tied to the breathing cycle.
The guidelines list a total of 11 authors representing The University of Texas MD Anderson Cancer Center; University of Florida, Jacksonville; University of Pennsylvania, Philadelphia; University of Louisiana, Baton Rouge; Proton Therapy Center Czech, Prague; Motol University Hospital, Czech Republic; St. Thomas and Guy Hospital, London; Institut Curie, Paris; and Rigshospitalet, Copenhagen.
Dr. Dabaja and her guideline coauthors reported no funding or conflicts of interest.
FROM BLOOD