Woman exercising in a park

Photo by Peter Griffin

ORLANDO, FL—Frailty after hematopoietic stem cell transplant (HSCT), while associated with higher mortality, is not necessarily a function of age, according to investigators studying the impact of frailty on transplant outcomes.

Instead, other factors, such as increasing time from transplant, employment status, medical leave or disability, and limitations of social activities, were significantly associated with higher odds of frailty.

The investigators prospectively studied 96 HSCT recipients, age 40 and older, to determine the prevalence of frailty in HSCT populations and its impact on outcomes, including early post-transplant non-relapse mortality (NRM).

Mukta Arora, MD, of the University of Minnesota in Minneapolis, reported the findings at the 2015 ASH Annual Meeting (abstract 388*).

The investigators defined frailty as the presence of 3 or more of the following criteria: low grip strength, exhaustion, slowed walking speed, low physical activity, and unintentional weight loss. They defined pre-frailty as having 1 or 2 of these characteristics.

The investigators conducted multi-domain geriatric assessments of patients prior to HSCT and after transplant at 100 days, 6 months, and 1 year. The assessment included function, comorbidity, cognition, psychological state, social activity/support, nutritional status, and demographic, transplant, and disease-related information.

Forty-eight patients were in the younger age group (40–59), and 48 were in the older age group (60–74). All had undergone HSCT between February 2014 and April 2015.

Patient demographics

Patients in the younger group were a median age of 54 (range, 40–59) at transplant. Sixty-five percent were male, 58% had an autologous transplant, and 79% received myeloablative conditioning.

Patients in the older group were a median age of 65 (range, 60–73) at transplant. Fifty-four percent were male, 46% had an autologous transplant, and 46% had myeloablative conditioning.

The difference between the older and younger groups in their conditioning regimen was significant (P<0.01).

The groups were comparable in terms of the HSCT comorbidity index but were significantly different in employment status (P<0.01).

“As expected,” Dr Arora said, “there were more patients who were retired in the older group.”

In the younger group, 31% were employed, 3% retired, 56% on medical leave or disabled, and 10% unemployed.

In the older group, 6% were employed, 62% retired, 28% on medical leave or disabled, and 4% unemployed.

“There was no difference in the social activity and social support scores between the 2 groups,” Dr Arora observed.

Frailty assessments

In the younger group, at baseline, the prevalence of pre-frailty was 47%, and the prevalence of frailty was 11%. At 6 months after HSCT, the prevalence of pre-frailty was 45%, and the prevalence of frailty was 41% (P<0.01).

In the older group, at baseline, the prevalence of pre-frailty was 42%, and the prevalence of frailty was 6%. At 6 months, the prevalence of pre-frailty was 44%, and the prevalence of frailty was 38% (P<0.01).

The investigators then estimated the predictors of frailty.

Significant predictors of frailty included time since HSCT (odds ratio [OR]=3.7, 95% CI: 1.9-7.2, P<0.01), employment status (retired: OR=7.3, 95% CI 1.2 – 46.2, P=0.03), on medical leave or disabled (OR=11.2, 95% CI: 1.8 – 67.7, P=0.01), limitations in social activities (OR=1.04, 95% CI: 1.01 – 1.08, P=0.01), and baseline pre-frailty (OR=3.1, 95% CI: 2.3 – 45.5, P<0.01).

Allogeneic transplant was associated with higher odds of frailty than autologous (OR=3.1, 95% CI: 0.9 – 10.2), although it did not reach significance (P=0.06).

Investigators next estimated the impact of frailty or pre-frailty on NRM and identified a trend toward increased NRM in frail patients.

The 46 patients classified as not frail at baseline had a 7% cumulative incidence of NRM (P=0.07). The 42 patients classified as pre-frail had a 23% cumulative incidence of NRM, while the 8 patients classified as frail at baseline had a 28% cumulative incidence of NRM.

“So, to conclude, in this early study, frailty was noted in 8% and pre-frailty in 44% of the transplant population prior to transplant, and was not dependent on age,” Dr Arora said. “Frailty is a transitional state and appears to reflect a dynamic progression from robustness to functional decline with time since [HSCT].”

Because frailty is associated with higher mortality, the investigators believe vulnerable populations should be identified and their need for specific interventions defined.

This research was funded by the Leukemia & Lymphoma Society.

*Data in the abstract differ from the presentation.

Woman exercising in a park

Photo by Peter Griffin

ORLANDO, FL—Frailty after hematopoietic stem cell transplant (HSCT), while associated with higher mortality, is not necessarily a function of age, according to investigators studying the impact of frailty on transplant outcomes.

Instead, other factors, such as increasing time from transplant, employment status, medical leave or disability, and limitations of social activities, were significantly associated with higher odds of frailty.

The investigators prospectively studied 96 HSCT recipients, age 40 and older, to determine the prevalence of frailty in HSCT populations and its impact on outcomes, including early post-transplant non-relapse mortality (NRM).

Mukta Arora, MD, of the University of Minnesota in Minneapolis, reported the findings at the 2015 ASH Annual Meeting (abstract 388*).

The investigators defined frailty as the presence of 3 or more of the following criteria: low grip strength, exhaustion, slowed walking speed, low physical activity, and unintentional weight loss. They defined pre-frailty as having 1 or 2 of these characteristics.

The investigators conducted multi-domain geriatric assessments of patients prior to HSCT and after transplant at 100 days, 6 months, and 1 year. The assessment included function, comorbidity, cognition, psychological state, social activity/support, nutritional status, and demographic, transplant, and disease-related information.

Forty-eight patients were in the younger age group (40–59), and 48 were in the older age group (60–74). All had undergone HSCT between February 2014 and April 2015.

Patient demographics

Patients in the younger group were a median age of 54 (range, 40–59) at transplant. Sixty-five percent were male, 58% had an autologous transplant, and 79% received myeloablative conditioning.

Patients in the older group were a median age of 65 (range, 60–73) at transplant. Fifty-four percent were male, 46% had an autologous transplant, and 46% had myeloablative conditioning.

The difference between the older and younger groups in their conditioning regimen was significant (P<0.01).

The groups were comparable in terms of the HSCT comorbidity index but were significantly different in employment status (P<0.01).

“As expected,” Dr Arora said, “there were more patients who were retired in the older group.”

In the younger group, 31% were employed, 3% retired, 56% on medical leave or disabled, and 10% unemployed.

In the older group, 6% were employed, 62% retired, 28% on medical leave or disabled, and 4% unemployed.

“There was no difference in the social activity and social support scores between the 2 groups,” Dr Arora observed.

Frailty assessments

In the younger group, at baseline, the prevalence of pre-frailty was 47%, and the prevalence of frailty was 11%. At 6 months after HSCT, the prevalence of pre-frailty was 45%, and the prevalence of frailty was 41% (P<0.01).

In the older group, at baseline, the prevalence of pre-frailty was 42%, and the prevalence of frailty was 6%. At 6 months, the prevalence of pre-frailty was 44%, and the prevalence of frailty was 38% (P<0.01).

The investigators then estimated the predictors of frailty.

Significant predictors of frailty included time since HSCT (odds ratio [OR]=3.7, 95% CI: 1.9-7.2, P<0.01), employment status (retired: OR=7.3, 95% CI 1.2 – 46.2, P=0.03), on medical leave or disabled (OR=11.2, 95% CI: 1.8 – 67.7, P=0.01), limitations in social activities (OR=1.04, 95% CI: 1.01 – 1.08, P=0.01), and baseline pre-frailty (OR=3.1, 95% CI: 2.3 – 45.5, P<0.01).

Allogeneic transplant was associated with higher odds of frailty than autologous (OR=3.1, 95% CI: 0.9 – 10.2), although it did not reach significance (P=0.06).

Investigators next estimated the impact of frailty or pre-frailty on NRM and identified a trend toward increased NRM in frail patients.

The 46 patients classified as not frail at baseline had a 7% cumulative incidence of NRM (P=0.07). The 42 patients classified as pre-frail had a 23% cumulative incidence of NRM, while the 8 patients classified as frail at baseline had a 28% cumulative incidence of NRM.

“So, to conclude, in this early study, frailty was noted in 8% and pre-frailty in 44% of the transplant population prior to transplant, and was not dependent on age,” Dr Arora said. “Frailty is a transitional state and appears to reflect a dynamic progression from robustness to functional decline with time since [HSCT].”

Because frailty is associated with higher mortality, the investigators believe vulnerable populations should be identified and their need for specific interventions defined.

This research was funded by the Leukemia & Lymphoma Society.

*Data in the abstract differ from the presentation.

Woman exercising in a park

Photo by Peter Griffin

ORLANDO, FL—Frailty after hematopoietic stem cell transplant (HSCT), while associated with higher mortality, is not necessarily a function of age, according to investigators studying the impact of frailty on transplant outcomes.

Instead, other factors, such as increasing time from transplant, employment status, medical leave or disability, and limitations of social activities, were significantly associated with higher odds of frailty.

The investigators prospectively studied 96 HSCT recipients, age 40 and older, to determine the prevalence of frailty in HSCT populations and its impact on outcomes, including early post-transplant non-relapse mortality (NRM).

Mukta Arora, MD, of the University of Minnesota in Minneapolis, reported the findings at the 2015 ASH Annual Meeting (abstract 388*).

The investigators defined frailty as the presence of 3 or more of the following criteria: low grip strength, exhaustion, slowed walking speed, low physical activity, and unintentional weight loss. They defined pre-frailty as having 1 or 2 of these characteristics.

The investigators conducted multi-domain geriatric assessments of patients prior to HSCT and after transplant at 100 days, 6 months, and 1 year. The assessment included function, comorbidity, cognition, psychological state, social activity/support, nutritional status, and demographic, transplant, and disease-related information.

Forty-eight patients were in the younger age group (40–59), and 48 were in the older age group (60–74). All had undergone HSCT between February 2014 and April 2015.

Patient demographics

Patients in the younger group were a median age of 54 (range, 40–59) at transplant. Sixty-five percent were male, 58% had an autologous transplant, and 79% received myeloablative conditioning.

Patients in the older group were a median age of 65 (range, 60–73) at transplant. Fifty-four percent were male, 46% had an autologous transplant, and 46% had myeloablative conditioning.

The difference between the older and younger groups in their conditioning regimen was significant (P<0.01).

The groups were comparable in terms of the HSCT comorbidity index but were significantly different in employment status (P<0.01).

“As expected,” Dr Arora said, “there were more patients who were retired in the older group.”

In the younger group, 31% were employed, 3% retired, 56% on medical leave or disabled, and 10% unemployed.

In the older group, 6% were employed, 62% retired, 28% on medical leave or disabled, and 4% unemployed.

“There was no difference in the social activity and social support scores between the 2 groups,” Dr Arora observed.

Frailty assessments

In the younger group, at baseline, the prevalence of pre-frailty was 47%, and the prevalence of frailty was 11%. At 6 months after HSCT, the prevalence of pre-frailty was 45%, and the prevalence of frailty was 41% (P<0.01).

In the older group, at baseline, the prevalence of pre-frailty was 42%, and the prevalence of frailty was 6%. At 6 months, the prevalence of pre-frailty was 44%, and the prevalence of frailty was 38% (P<0.01).

The investigators then estimated the predictors of frailty.

Significant predictors of frailty included time since HSCT (odds ratio [OR]=3.7, 95% CI: 1.9-7.2, P<0.01), employment status (retired: OR=7.3, 95% CI 1.2 – 46.2, P=0.03), on medical leave or disabled (OR=11.2, 95% CI: 1.8 – 67.7, P=0.01), limitations in social activities (OR=1.04, 95% CI: 1.01 – 1.08, P=0.01), and baseline pre-frailty (OR=3.1, 95% CI: 2.3 – 45.5, P<0.01).

Allogeneic transplant was associated with higher odds of frailty than autologous (OR=3.1, 95% CI: 0.9 – 10.2), although it did not reach significance (P=0.06).

Investigators next estimated the impact of frailty or pre-frailty on NRM and identified a trend toward increased NRM in frail patients.

The 46 patients classified as not frail at baseline had a 7% cumulative incidence of NRM (P=0.07). The 42 patients classified as pre-frail had a 23% cumulative incidence of NRM, while the 8 patients classified as frail at baseline had a 28% cumulative incidence of NRM.

“So, to conclude, in this early study, frailty was noted in 8% and pre-frailty in 44% of the transplant population prior to transplant, and was not dependent on age,” Dr Arora said. “Frailty is a transitional state and appears to reflect a dynamic progression from robustness to functional decline with time since [HSCT].”

Because frailty is associated with higher mortality, the investigators believe vulnerable populations should be identified and their need for specific interventions defined.

This research was funded by the Leukemia & Lymphoma Society.

*Data in the abstract differ from the presentation.

Jesús San-Miguel, MD, PhD

Photo courtesy of the

University of Navarra

ORLANDO, FL—The addition of panobinostat to bortezomib-dexamethasone therapy in relapsed or refractory multiple myeloma (MM) patients can double the rate of deep responses and prolong progression-free survival (PFS), according to an updated analysis of data from the PANORMA 1 trial.

Panobinostat, a pan-deacetylase inhibitor, was the first agent of its class to produce a statistically significant and clinically meaningful increase in the median PFS of patients with relapsed/refractory MM in a phase 3 trial, noted Jesús F. San-Miguel, MD, PhD, of the University of Navarra in Pamplona, Spain.

Dr San-Miguel presented results of the updated analysis at the 2015 ASH Annual Meeting (abstract 4230).

In the PANORAMA 1 trial, patients receiving panobinostat plus bortezomib and dexamethasone had a significantly prolonged median PFS of 12 months versus 8.1 months in patients treated with placebo-bortezomib-dexamethasone.

A subgroup analysis showed that the PFS benefit was improved in patients with previous exposure to bortezomib and immunomodulatory drugs (IMiDs). The addition of panobinostat to bortezomib-dexamethasone also led to a significant increase in high-quality responses.

With their analysis, Dr San-Miguel and his colleagues set out to determine the effect of responses on clinical outcomes of patients treated in PANORAMA 1, including those with prior exposure to bortezomib and IMiDs.

The researchers conducted a landmark analysis at 12, 18, and 24 weeks to assess the median PFS in patients who achieved a complete response (CR)/near complete response (nCR) or partial response (PR).

“For the total study population, the rates of high-quality responses [CR/nCR rate] were significantly higher in the panobinostat-bortezomib-dexamethasone arm [28%] than in the control arm [16%],” Dr San-Miguel said.

Among the subgroup with prior exposure to bortezomib and IMiDs, the CR/nCR rate was also higher in the triple-drug arm (22.3%) than in the 2-drug arm (9.9%).

Among patients who took panobinostat-bortezomib-dexamethasone, the duration of response was twice as long in those who achieved CR/nCR (18.4 months) as in those who achieved a PR (9 months).

The median PFS at 12 weeks for patients who received panobinostat-bortezomib-dexamethasone was increased in patients achieving high-quality responses: 16.5 months for nCR as compared to 10.3 months for PR.

The subgroup of patients with prior exposure to bortezomib and IMiDs who achieved deeper responses also demonstrated longer PFS at 12 weeks: a median of 13.7 months for nCR and 8.1 months for PR.

“In both the overall study population and the subgroup of patients with prior exposure to bortezomib and IMiDs, a 2-fold increase in deep responses was achieved with panobinostat-bortezomib-dexamethasone compared with placebo-bortezomib-dexamethasone,” Dr San-Miguel said. “In both groups, deep responses were associated with a prolonged PFS and a longer duration of response.”

He noted that the magnitude of benefit at each time point appeared greater among patients who received the triple-drug combination.

“These data further support achievement of deeper responses as a treatment goal and a robust and consistent benefit of panobinostat in the phase 3 study in patients with relapsed/refractory multiple myeloma, including those with prior exposure to bortezomib and IMiDs,” Dr San-Miguel said.

The PANORAMA 1 trial was sponsored by Novartis, the company developing panobinostat. Three researchers involved in the current analysis are employees of Novartis, and other researchers reported having relationships (receiving research funding, consulting, etc.) with a range of other pharmaceutical companies.

Jesús San-Miguel, MD, PhD

Photo courtesy of the

University of Navarra

ORLANDO, FL—The addition of panobinostat to bortezomib-dexamethasone therapy in relapsed or refractory multiple myeloma (MM) patients can double the rate of deep responses and prolong progression-free survival (PFS), according to an updated analysis of data from the PANORMA 1 trial.

Panobinostat, a pan-deacetylase inhibitor, was the first agent of its class to produce a statistically significant and clinically meaningful increase in the median PFS of patients with relapsed/refractory MM in a phase 3 trial, noted Jesús F. San-Miguel, MD, PhD, of the University of Navarra in Pamplona, Spain.

Dr San-Miguel presented results of the updated analysis at the 2015 ASH Annual Meeting (abstract 4230).

In the PANORAMA 1 trial, patients receiving panobinostat plus bortezomib and dexamethasone had a significantly prolonged median PFS of 12 months versus 8.1 months in patients treated with placebo-bortezomib-dexamethasone.

A subgroup analysis showed that the PFS benefit was improved in patients with previous exposure to bortezomib and immunomodulatory drugs (IMiDs). The addition of panobinostat to bortezomib-dexamethasone also led to a significant increase in high-quality responses.

With their analysis, Dr San-Miguel and his colleagues set out to determine the effect of responses on clinical outcomes of patients treated in PANORAMA 1, including those with prior exposure to bortezomib and IMiDs.

The researchers conducted a landmark analysis at 12, 18, and 24 weeks to assess the median PFS in patients who achieved a complete response (CR)/near complete response (nCR) or partial response (PR).

“For the total study population, the rates of high-quality responses [CR/nCR rate] were significantly higher in the panobinostat-bortezomib-dexamethasone arm [28%] than in the control arm [16%],” Dr San-Miguel said.

Among the subgroup with prior exposure to bortezomib and IMiDs, the CR/nCR rate was also higher in the triple-drug arm (22.3%) than in the 2-drug arm (9.9%).

Among patients who took panobinostat-bortezomib-dexamethasone, the duration of response was twice as long in those who achieved CR/nCR (18.4 months) as in those who achieved a PR (9 months).

The median PFS at 12 weeks for patients who received panobinostat-bortezomib-dexamethasone was increased in patients achieving high-quality responses: 16.5 months for nCR as compared to 10.3 months for PR.

The subgroup of patients with prior exposure to bortezomib and IMiDs who achieved deeper responses also demonstrated longer PFS at 12 weeks: a median of 13.7 months for nCR and 8.1 months for PR.

“In both the overall study population and the subgroup of patients with prior exposure to bortezomib and IMiDs, a 2-fold increase in deep responses was achieved with panobinostat-bortezomib-dexamethasone compared with placebo-bortezomib-dexamethasone,” Dr San-Miguel said. “In both groups, deep responses were associated with a prolonged PFS and a longer duration of response.”

He noted that the magnitude of benefit at each time point appeared greater among patients who received the triple-drug combination.

“These data further support achievement of deeper responses as a treatment goal and a robust and consistent benefit of panobinostat in the phase 3 study in patients with relapsed/refractory multiple myeloma, including those with prior exposure to bortezomib and IMiDs,” Dr San-Miguel said.

The PANORAMA 1 trial was sponsored by Novartis, the company developing panobinostat. Three researchers involved in the current analysis are employees of Novartis, and other researchers reported having relationships (receiving research funding, consulting, etc.) with a range of other pharmaceutical companies.

Jesús San-Miguel, MD, PhD

Photo courtesy of the

University of Navarra

ORLANDO, FL—The addition of panobinostat to bortezomib-dexamethasone therapy in relapsed or refractory multiple myeloma (MM) patients can double the rate of deep responses and prolong progression-free survival (PFS), according to an updated analysis of data from the PANORMA 1 trial.

Panobinostat, a pan-deacetylase inhibitor, was the first agent of its class to produce a statistically significant and clinically meaningful increase in the median PFS of patients with relapsed/refractory MM in a phase 3 trial, noted Jesús F. San-Miguel, MD, PhD, of the University of Navarra in Pamplona, Spain.

Dr San-Miguel presented results of the updated analysis at the 2015 ASH Annual Meeting (abstract 4230).

In the PANORAMA 1 trial, patients receiving panobinostat plus bortezomib and dexamethasone had a significantly prolonged median PFS of 12 months versus 8.1 months in patients treated with placebo-bortezomib-dexamethasone.

A subgroup analysis showed that the PFS benefit was improved in patients with previous exposure to bortezomib and immunomodulatory drugs (IMiDs). The addition of panobinostat to bortezomib-dexamethasone also led to a significant increase in high-quality responses.

With their analysis, Dr San-Miguel and his colleagues set out to determine the effect of responses on clinical outcomes of patients treated in PANORAMA 1, including those with prior exposure to bortezomib and IMiDs.

The researchers conducted a landmark analysis at 12, 18, and 24 weeks to assess the median PFS in patients who achieved a complete response (CR)/near complete response (nCR) or partial response (PR).

“For the total study population, the rates of high-quality responses [CR/nCR rate] were significantly higher in the panobinostat-bortezomib-dexamethasone arm [28%] than in the control arm [16%],” Dr San-Miguel said.

Among the subgroup with prior exposure to bortezomib and IMiDs, the CR/nCR rate was also higher in the triple-drug arm (22.3%) than in the 2-drug arm (9.9%).

Among patients who took panobinostat-bortezomib-dexamethasone, the duration of response was twice as long in those who achieved CR/nCR (18.4 months) as in those who achieved a PR (9 months).

The median PFS at 12 weeks for patients who received panobinostat-bortezomib-dexamethasone was increased in patients achieving high-quality responses: 16.5 months for nCR as compared to 10.3 months for PR.

The subgroup of patients with prior exposure to bortezomib and IMiDs who achieved deeper responses also demonstrated longer PFS at 12 weeks: a median of 13.7 months for nCR and 8.1 months for PR.

“In both the overall study population and the subgroup of patients with prior exposure to bortezomib and IMiDs, a 2-fold increase in deep responses was achieved with panobinostat-bortezomib-dexamethasone compared with placebo-bortezomib-dexamethasone,” Dr San-Miguel said. “In both groups, deep responses were associated with a prolonged PFS and a longer duration of response.”

He noted that the magnitude of benefit at each time point appeared greater among patients who received the triple-drug combination.

“These data further support achievement of deeper responses as a treatment goal and a robust and consistent benefit of panobinostat in the phase 3 study in patients with relapsed/refractory multiple myeloma, including those with prior exposure to bortezomib and IMiDs,” Dr San-Miguel said.

The PANORAMA 1 trial was sponsored by Novartis, the company developing panobinostat. Three researchers involved in the current analysis are employees of Novartis, and other researchers reported having relationships (receiving research funding, consulting, etc.) with a range of other pharmaceutical companies.

Preparing treatment

for a clinical trial

Photo by Esther Dyson

Twelve factors may predict low patient accrual in cancer clinical trials, according to research published in JNCI.

Many studies have been conducted to investigate the perceived barriers to clinical trial accrual from the patient or provider perspective.

However, researchers have rarely taken a trial-level view and investigated why certain trials are able to accrue patients faster than expected while others fail to attract even a fraction of the intended number of participants.

Caroline S. Bennette, PhD, of the University of Washington in Seattle, and her colleagues conducted their study to do just that.

They analyzed information on 787 phase 2/3 clinical trials sponsored by the National Clinical Trials Network (NCTN; formerly the Cooperative Group Program) launched between 2000 and 2011.

After excluding trials that closed because of toxicity or interim results, the researchers found that 145 (18%) NCTN trials closed with low accrual or were accruing at less than 50% of target accrual 3 years or more after opening.

The team identified potential risk factors from the literature and interviews with clinical trial experts and found multiple trial-level factors that were associated with poor accrual to NCTN trials, such as increased competition for patients from currently ongoing trials, planning to enroll a higher proportion of the available patient population, and not evaluating a new investigational agent or targeted therapy.

The researchers then developed a multivariable prediction model of low accrual using 12 trial-level risk factors. The team said these factors had good agreement between predicted and observed risks of low accrual in a preliminary validation using 46 trials opened between 2012 and 2013.

Those 12 risk factors are:

1. The number of competing trials per 10,000 eligible patients per year (odds ratio [OR]=1.88)
2. Phase 3 vs phase 2 trial (OR=1.86)
3. Enrollment as percentage of eligible population for targeted therapy (OR=0.57)
4. Enrollment as percentage of eligible population for radiation therapy (OR=1.81)
5. Annual incidence of clinical condition(s) per 10,000 (OR=0.99)
6. Tissue sample required to assess eligibility (OR=1.26)
7. Investigational new drug (OR=0.34)
8. Metastatic setting (OR=1.46)
9. Sample size per 100 (OR=0.95)
10. More than one condition evaluated (OR=1.98)
11. Common solid cancer (prostate, breast, lung, or colon) vs liquid or rare solid cancers (OR=2.32)
12. Interaction term (phase 3 x investigational new drug, OR=2.47).

The researchers concluded that systematically considering the overall influence of these risk factors could aid in the design and prioritization of future clinical trials.

Preparing treatment

for a clinical trial

Photo by Esther Dyson

Twelve factors may predict low patient accrual in cancer clinical trials, according to research published in JNCI.

Many studies have been conducted to investigate the perceived barriers to clinical trial accrual from the patient or provider perspective.

However, researchers have rarely taken a trial-level view and investigated why certain trials are able to accrue patients faster than expected while others fail to attract even a fraction of the intended number of participants.

Caroline S. Bennette, PhD, of the University of Washington in Seattle, and her colleagues conducted their study to do just that.

They analyzed information on 787 phase 2/3 clinical trials sponsored by the National Clinical Trials Network (NCTN; formerly the Cooperative Group Program) launched between 2000 and 2011.

After excluding trials that closed because of toxicity or interim results, the researchers found that 145 (18%) NCTN trials closed with low accrual or were accruing at less than 50% of target accrual 3 years or more after opening.

The team identified potential risk factors from the literature and interviews with clinical trial experts and found multiple trial-level factors that were associated with poor accrual to NCTN trials, such as increased competition for patients from currently ongoing trials, planning to enroll a higher proportion of the available patient population, and not evaluating a new investigational agent or targeted therapy.

The researchers then developed a multivariable prediction model of low accrual using 12 trial-level risk factors. The team said these factors had good agreement between predicted and observed risks of low accrual in a preliminary validation using 46 trials opened between 2012 and 2013.

Those 12 risk factors are:

1. The number of competing trials per 10,000 eligible patients per year (odds ratio [OR]=1.88)
2. Phase 3 vs phase 2 trial (OR=1.86)
3. Enrollment as percentage of eligible population for targeted therapy (OR=0.57)
4. Enrollment as percentage of eligible population for radiation therapy (OR=1.81)
5. Annual incidence of clinical condition(s) per 10,000 (OR=0.99)
6. Tissue sample required to assess eligibility (OR=1.26)
7. Investigational new drug (OR=0.34)
8. Metastatic setting (OR=1.46)
9. Sample size per 100 (OR=0.95)
10. More than one condition evaluated (OR=1.98)
11. Common solid cancer (prostate, breast, lung, or colon) vs liquid or rare solid cancers (OR=2.32)
12. Interaction term (phase 3 x investigational new drug, OR=2.47).

The researchers concluded that systematically considering the overall influence of these risk factors could aid in the design and prioritization of future clinical trials.

Preparing treatment

for a clinical trial

Photo by Esther Dyson

Twelve factors may predict low patient accrual in cancer clinical trials, according to research published in JNCI.

Many studies have been conducted to investigate the perceived barriers to clinical trial accrual from the patient or provider perspective.

However, researchers have rarely taken a trial-level view and investigated why certain trials are able to accrue patients faster than expected while others fail to attract even a fraction of the intended number of participants.

Caroline S. Bennette, PhD, of the University of Washington in Seattle, and her colleagues conducted their study to do just that.

They analyzed information on 787 phase 2/3 clinical trials sponsored by the National Clinical Trials Network (NCTN; formerly the Cooperative Group Program) launched between 2000 and 2011.

After excluding trials that closed because of toxicity or interim results, the researchers found that 145 (18%) NCTN trials closed with low accrual or were accruing at less than 50% of target accrual 3 years or more after opening.

The team identified potential risk factors from the literature and interviews with clinical trial experts and found multiple trial-level factors that were associated with poor accrual to NCTN trials, such as increased competition for patients from currently ongoing trials, planning to enroll a higher proportion of the available patient population, and not evaluating a new investigational agent or targeted therapy.

The researchers then developed a multivariable prediction model of low accrual using 12 trial-level risk factors. The team said these factors had good agreement between predicted and observed risks of low accrual in a preliminary validation using 46 trials opened between 2012 and 2013.

Those 12 risk factors are:

1. The number of competing trials per 10,000 eligible patients per year (odds ratio [OR]=1.88)
2. Phase 3 vs phase 2 trial (OR=1.86)
3. Enrollment as percentage of eligible population for targeted therapy (OR=0.57)
4. Enrollment as percentage of eligible population for radiation therapy (OR=1.81)
5. Annual incidence of clinical condition(s) per 10,000 (OR=0.99)
6. Tissue sample required to assess eligibility (OR=1.26)
7. Investigational new drug (OR=0.34)
8. Metastatic setting (OR=1.46)
9. Sample size per 100 (OR=0.95)
10. More than one condition evaluated (OR=1.98)
11. Common solid cancer (prostate, breast, lung, or colon) vs liquid or rare solid cancers (OR=2.32)
12. Interaction term (phase 3 x investigational new drug, OR=2.47).

The researchers concluded that systematically considering the overall influence of these risk factors could aid in the design and prioritization of future clinical trials.

Axel Kallies, PhD, and

Diana Hansen, PhD

Photo courtesy of the Walter

and Eliza Hall Institute

Results of preclinical research appear to explain how the malaria parasite Plasmodium falciparum causes an inflammatory reaction that sabotages the body’s ability to protect itself from malaria.

Researchers found evidence to suggest that the same inflammatory molecules that drive the immune response in clinical and severe malaria also prevent the body from developing protective antibodies against the parasite.

They said this discovery opens up the possibility of improving new or existing malaria vaccines by boosting immune cells needed for long-lasting immunity.

Diana Hansen, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues described this work in Cell Reports.

Dr Hansen said this is the first time scientists have pinpointed why the immune system fails to develop immunity during malaria infection.

“With many infections, a single exposure to the pathogen is enough to induce production of antibodies that will protect you for the rest of your life,” she explained. “However, with malaria, it can take up to 20 years for someone to build up sufficient immunity to be protected.”

The fact that the body is not good at developing long-lasting immunity to the parasite has hampered vaccine development, Dr Hansen added.

“This was complicated by the fact that we didn’t know whether it was the malaria parasite itself or the inflammatory reaction to malaria that was actually inhibiting the ability to develop protective immunity,” she said.

“We have now shown that it was a double-edged sword. The strong inflammatory reaction that accompanies and, in fact, drives severe clinical malaria is also responsible for silencing the key immune cells needed for long-term protection against the parasite.”

Dr Hansen and her colleagues conducted experiments in mouse models of malaria and found that inflammatory molecules released by the body to fight the infection were preventing protective antibodies from being made.

“Specialized immune cells called helper T cells join forces with B cells to generate these protective antibodies,” said Axel Kallies, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“However, we showed that, during malaria infection, critical inflammatory molecules actually arrest development of helper T cells, and, therefore, the B cells don’t get the necessary instructions to make antibodies.”

Specifically, the researchers found that severe malaria infection inhibited the establishment of germinal centers in the spleens of the mice. And malaria infection induced high frequencies of T-follicular-helper cell precursors but resulted in impaired T-follicular-helper cell differentiation.

Precursor T-follicular-helper cells induced during infection had low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3.

However, when the researchers blocked the inflammatory cytokines TNF and IFN-γ or deleted T-bet, they were able to restore T-follicular-helper cell differentiation and germinal center responses to infection.

Dr Hansen said these findings could lead to new avenues in the search for effective malaria vaccines.

“This research opens the door to therapeutic approaches to accelerate development of protective immunity to malaria and improve efficacy of malaria vaccines,” she said.

“Until now, malaria vaccines have had disappointing results. We can now see a way of improving these responses by tailoring or augmenting the vaccine to boost development of helper T cells that will enable the body to make protective antibodies that target the malaria parasites.”

Axel Kallies, PhD, and

Diana Hansen, PhD

Photo courtesy of the Walter

and Eliza Hall Institute

Results of preclinical research appear to explain how the malaria parasite Plasmodium falciparum causes an inflammatory reaction that sabotages the body’s ability to protect itself from malaria.

Researchers found evidence to suggest that the same inflammatory molecules that drive the immune response in clinical and severe malaria also prevent the body from developing protective antibodies against the parasite.

They said this discovery opens up the possibility of improving new or existing malaria vaccines by boosting immune cells needed for long-lasting immunity.

Diana Hansen, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues described this work in Cell Reports.

Dr Hansen said this is the first time scientists have pinpointed why the immune system fails to develop immunity during malaria infection.

“With many infections, a single exposure to the pathogen is enough to induce production of antibodies that will protect you for the rest of your life,” she explained. “However, with malaria, it can take up to 20 years for someone to build up sufficient immunity to be protected.”

The fact that the body is not good at developing long-lasting immunity to the parasite has hampered vaccine development, Dr Hansen added.

“This was complicated by the fact that we didn’t know whether it was the malaria parasite itself or the inflammatory reaction to malaria that was actually inhibiting the ability to develop protective immunity,” she said.

“We have now shown that it was a double-edged sword. The strong inflammatory reaction that accompanies and, in fact, drives severe clinical malaria is also responsible for silencing the key immune cells needed for long-term protection against the parasite.”

Dr Hansen and her colleagues conducted experiments in mouse models of malaria and found that inflammatory molecules released by the body to fight the infection were preventing protective antibodies from being made.

“Specialized immune cells called helper T cells join forces with B cells to generate these protective antibodies,” said Axel Kallies, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“However, we showed that, during malaria infection, critical inflammatory molecules actually arrest development of helper T cells, and, therefore, the B cells don’t get the necessary instructions to make antibodies.”

Specifically, the researchers found that severe malaria infection inhibited the establishment of germinal centers in the spleens of the mice. And malaria infection induced high frequencies of T-follicular-helper cell precursors but resulted in impaired T-follicular-helper cell differentiation.

Precursor T-follicular-helper cells induced during infection had low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3.

However, when the researchers blocked the inflammatory cytokines TNF and IFN-γ or deleted T-bet, they were able to restore T-follicular-helper cell differentiation and germinal center responses to infection.

Dr Hansen said these findings could lead to new avenues in the search for effective malaria vaccines.

“This research opens the door to therapeutic approaches to accelerate development of protective immunity to malaria and improve efficacy of malaria vaccines,” she said.

“Until now, malaria vaccines have had disappointing results. We can now see a way of improving these responses by tailoring or augmenting the vaccine to boost development of helper T cells that will enable the body to make protective antibodies that target the malaria parasites.”

Axel Kallies, PhD, and

Diana Hansen, PhD

Photo courtesy of the Walter

and Eliza Hall Institute

Results of preclinical research appear to explain how the malaria parasite Plasmodium falciparum causes an inflammatory reaction that sabotages the body’s ability to protect itself from malaria.

Researchers found evidence to suggest that the same inflammatory molecules that drive the immune response in clinical and severe malaria also prevent the body from developing protective antibodies against the parasite.

They said this discovery opens up the possibility of improving new or existing malaria vaccines by boosting immune cells needed for long-lasting immunity.

Diana Hansen, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and her colleagues described this work in Cell Reports.

Dr Hansen said this is the first time scientists have pinpointed why the immune system fails to develop immunity during malaria infection.

“With many infections, a single exposure to the pathogen is enough to induce production of antibodies that will protect you for the rest of your life,” she explained. “However, with malaria, it can take up to 20 years for someone to build up sufficient immunity to be protected.”

The fact that the body is not good at developing long-lasting immunity to the parasite has hampered vaccine development, Dr Hansen added.

“This was complicated by the fact that we didn’t know whether it was the malaria parasite itself or the inflammatory reaction to malaria that was actually inhibiting the ability to develop protective immunity,” she said.

“We have now shown that it was a double-edged sword. The strong inflammatory reaction that accompanies and, in fact, drives severe clinical malaria is also responsible for silencing the key immune cells needed for long-term protection against the parasite.”

Dr Hansen and her colleagues conducted experiments in mouse models of malaria and found that inflammatory molecules released by the body to fight the infection were preventing protective antibodies from being made.

“Specialized immune cells called helper T cells join forces with B cells to generate these protective antibodies,” said Axel Kallies, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“However, we showed that, during malaria infection, critical inflammatory molecules actually arrest development of helper T cells, and, therefore, the B cells don’t get the necessary instructions to make antibodies.”

Specifically, the researchers found that severe malaria infection inhibited the establishment of germinal centers in the spleens of the mice. And malaria infection induced high frequencies of T-follicular-helper cell precursors but resulted in impaired T-follicular-helper cell differentiation.

Precursor T-follicular-helper cells induced during infection had low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3.

However, when the researchers blocked the inflammatory cytokines TNF and IFN-γ or deleted T-bet, they were able to restore T-follicular-helper cell differentiation and germinal center responses to infection.

Dr Hansen said these findings could lead to new avenues in the search for effective malaria vaccines.

“This research opens the door to therapeutic approaches to accelerate development of protective immunity to malaria and improve efficacy of malaria vaccines,” she said.

“Until now, malaria vaccines have had disappointing results. We can now see a way of improving these responses by tailoring or augmenting the vaccine to boost development of helper T cells that will enable the body to make protective antibodies that target the malaria parasites.”

Screening for and treating high blood pressure (HBP) to prevent cardiovascular and renal disease is a tried-and-true preventive intervention that is supported by strong evidence. And not surprisingly, when the US Preventive Services Task Force (USPSTF) recently updated its 2007 recommendation for blood pressure screening for adults, it once again gave an A recommendation for those ages 18 years and older. What is noteworthy, however, is that this update concentrates on the accuracy of blood pressure measurement methods and optimal frequency of screening.¹

The most significant modification of past recommendations is that HBP found with office measurement of blood pressure (OMBP) should be confirmed with either ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) before starting treatment. (For its recommendation, the USPSTF used the HBP definition from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [TABLE 1].^2,3)

Ensuring accurate blood-pressure measurements. More than 30% of adults in the United States have HBP, with prevalence increasing with age (TABLE 2).² Only about half of this population has HBP under control.⁴ This modifiable condition contributes to more than 360,000 deaths annually.² However, while treatment of true HBP results in substantial benefits, it is important not to over-diagnose HBP and over-treat it.

Studies have shown that 15% to 30% of individuals diagnosed with HBP in a clinical setting will have blood pressure in the normal range when measurements are taken outside of the doctor’s office.¹ This discrepancy can be due to measurement error, regression to the mean, recent caffeine ingestion by the patient, or isolated clinical hypertension wherein the stress and anxiety caused by clinic visits elevates blood pressure transiently.

With this in mind, the USPSTF recommends that OMBP-detected HBP be confirmed with either ABPM or HBPM. Of these 2 follow-up methods, ABPM is supported by stronger evidence and is preferred. The USPSTF includes HBPM as an alternative because ABPM equipment may not always be available—or affordable—and using the equipment may present logistical challenges.

Starting off on the right foot

Screening for HBP in a clinical setting is more accurate if conducted according to recommended procedures: use an appropriately sized cuff; take the measurement at least 5 minutes after the patient’s arrival while he or she is seated with legs uncrossed and the cuffed arm is at the level of the heart; and record the mean of 2 separate measurements. There appears to be no real difference in the accuracy of automated vs manual sphygmomanometers.

Optimal frequency of screening varies. While the USPSTF found little evidence to support any particular overall screening frequency, it recommends annual screening for those who are 40 years of age or older and those ages 18 to 39 who are obese or overweight, are African American, or who have high-normal blood pressure (TABLE 3).¹ Screening every 3 to 5 years is recommended for individuals not in these categories.

Initial steps in treating HBP. The Task Force also commented on which medications to use when initiating HBP treatment (after lifestyle and dietary interventions). Non-African Americans should receive a thiazide diuretic, calcium channel blocker, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. African Americans should begin treatment with a thiazide diuretic or calcium channel blocker. These recommendations appear to have been adopted from the Eighth Joint National Committee, since the accompanying evidence report for the USPSTF’s update did not address this issue.⁵

Don't forget patient support

Patient support is key. As of June 2015, the Community Preventive Services Task Force (CPSTF) recommends self-measured blood pressure monitoring combined with additional support as a means of improving blood pressure control in those with HBP.⁴

Supportive measures include things such as patient counseling on medications and health behavior changes (eg, diet and exercise); education on HBP and blood pressure self-management; and use of secure electronic or Web-based tools such as text or e-mail reminders to measure blood pressure, show up for appointments, or communicate blood pressure readings to healthcare providers. Patients who participate in home self-measurement of blood pressure with additional support lower their systolic blood pressure, on average, 1.4 mm Hg more than those who do not.⁴

Remaining questions

The new USPSTF recommendation leaves several issues unaddressed. For one thing, the Affordable Care Act mandates that commercial health insurance plans provide services with an A or B Task Force recommendation to patients with no copayments. So does the new HBP recommendation mean payers have to make ABPM and HBPM available to patients at no charge?

Up to 30% of individuals diagnosed with high BP in a clinical setting will have BP in the normal range when measurements are taken outside of the doctor's office.

There are other questions, too. If HBP detected by OMBP is not confirmed when ABPM is performed, should ABPM be repeated, and if so, at what interval? What is the role of emerging technologies that use devices other than arm cuffs to measure blood pressure?

Despite these uncertainties, the new USPSTF and CPSTF recommendations refine the longstanding in-office–only approach to diagnosing and monitoring HBP and advocate newer technologies that could help improve diagnostic accuracy, avoid over-diagnosis and over-treatment, and improve patient adherence to treatment goals.

Screening for and treating high blood pressure (HBP) to prevent cardiovascular and renal disease is a tried-and-true preventive intervention that is supported by strong evidence. And not surprisingly, when the US Preventive Services Task Force (USPSTF) recently updated its 2007 recommendation for blood pressure screening for adults, it once again gave an A recommendation for those ages 18 years and older. What is noteworthy, however, is that this update concentrates on the accuracy of blood pressure measurement methods and optimal frequency of screening.¹

The most significant modification of past recommendations is that HBP found with office measurement of blood pressure (OMBP) should be confirmed with either ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) before starting treatment. (For its recommendation, the USPSTF used the HBP definition from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [TABLE 1].^2,3)

Ensuring accurate blood-pressure measurements. More than 30% of adults in the United States have HBP, with prevalence increasing with age (TABLE 2).² Only about half of this population has HBP under control.⁴ This modifiable condition contributes to more than 360,000 deaths annually.² However, while treatment of true HBP results in substantial benefits, it is important not to over-diagnose HBP and over-treat it.

Studies have shown that 15% to 30% of individuals diagnosed with HBP in a clinical setting will have blood pressure in the normal range when measurements are taken outside of the doctor’s office.¹ This discrepancy can be due to measurement error, regression to the mean, recent caffeine ingestion by the patient, or isolated clinical hypertension wherein the stress and anxiety caused by clinic visits elevates blood pressure transiently.

With this in mind, the USPSTF recommends that OMBP-detected HBP be confirmed with either ABPM or HBPM. Of these 2 follow-up methods, ABPM is supported by stronger evidence and is preferred. The USPSTF includes HBPM as an alternative because ABPM equipment may not always be available—or affordable—and using the equipment may present logistical challenges.

Starting off on the right foot

Screening for HBP in a clinical setting is more accurate if conducted according to recommended procedures: use an appropriately sized cuff; take the measurement at least 5 minutes after the patient’s arrival while he or she is seated with legs uncrossed and the cuffed arm is at the level of the heart; and record the mean of 2 separate measurements. There appears to be no real difference in the accuracy of automated vs manual sphygmomanometers.

Optimal frequency of screening varies. While the USPSTF found little evidence to support any particular overall screening frequency, it recommends annual screening for those who are 40 years of age or older and those ages 18 to 39 who are obese or overweight, are African American, or who have high-normal blood pressure (TABLE 3).¹ Screening every 3 to 5 years is recommended for individuals not in these categories.

Initial steps in treating HBP. The Task Force also commented on which medications to use when initiating HBP treatment (after lifestyle and dietary interventions). Non-African Americans should receive a thiazide diuretic, calcium channel blocker, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. African Americans should begin treatment with a thiazide diuretic or calcium channel blocker. These recommendations appear to have been adopted from the Eighth Joint National Committee, since the accompanying evidence report for the USPSTF’s update did not address this issue.⁵

Don't forget patient support

Patient support is key. As of June 2015, the Community Preventive Services Task Force (CPSTF) recommends self-measured blood pressure monitoring combined with additional support as a means of improving blood pressure control in those with HBP.⁴

Supportive measures include things such as patient counseling on medications and health behavior changes (eg, diet and exercise); education on HBP and blood pressure self-management; and use of secure electronic or Web-based tools such as text or e-mail reminders to measure blood pressure, show up for appointments, or communicate blood pressure readings to healthcare providers. Patients who participate in home self-measurement of blood pressure with additional support lower their systolic blood pressure, on average, 1.4 mm Hg more than those who do not.⁴

Remaining questions

The new USPSTF recommendation leaves several issues unaddressed. For one thing, the Affordable Care Act mandates that commercial health insurance plans provide services with an A or B Task Force recommendation to patients with no copayments. So does the new HBP recommendation mean payers have to make ABPM and HBPM available to patients at no charge?

Up to 30% of individuals diagnosed with high BP in a clinical setting will have BP in the normal range when measurements are taken outside of the doctor's office.

There are other questions, too. If HBP detected by OMBP is not confirmed when ABPM is performed, should ABPM be repeated, and if so, at what interval? What is the role of emerging technologies that use devices other than arm cuffs to measure blood pressure?

Despite these uncertainties, the new USPSTF and CPSTF recommendations refine the longstanding in-office–only approach to diagnosing and monitoring HBP and advocate newer technologies that could help improve diagnostic accuracy, avoid over-diagnosis and over-treatment, and improve patient adherence to treatment goals.

Screening for and treating high blood pressure (HBP) to prevent cardiovascular and renal disease is a tried-and-true preventive intervention that is supported by strong evidence. And not surprisingly, when the US Preventive Services Task Force (USPSTF) recently updated its 2007 recommendation for blood pressure screening for adults, it once again gave an A recommendation for those ages 18 years and older. What is noteworthy, however, is that this update concentrates on the accuracy of blood pressure measurement methods and optimal frequency of screening.¹

The most significant modification of past recommendations is that HBP found with office measurement of blood pressure (OMBP) should be confirmed with either ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) before starting treatment. (For its recommendation, the USPSTF used the HBP definition from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [TABLE 1].^2,3)

Ensuring accurate blood-pressure measurements. More than 30% of adults in the United States have HBP, with prevalence increasing with age (TABLE 2).² Only about half of this population has HBP under control.⁴ This modifiable condition contributes to more than 360,000 deaths annually.² However, while treatment of true HBP results in substantial benefits, it is important not to over-diagnose HBP and over-treat it.

Studies have shown that 15% to 30% of individuals diagnosed with HBP in a clinical setting will have blood pressure in the normal range when measurements are taken outside of the doctor’s office.¹ This discrepancy can be due to measurement error, regression to the mean, recent caffeine ingestion by the patient, or isolated clinical hypertension wherein the stress and anxiety caused by clinic visits elevates blood pressure transiently.

With this in mind, the USPSTF recommends that OMBP-detected HBP be confirmed with either ABPM or HBPM. Of these 2 follow-up methods, ABPM is supported by stronger evidence and is preferred. The USPSTF includes HBPM as an alternative because ABPM equipment may not always be available—or affordable—and using the equipment may present logistical challenges.

Starting off on the right foot

Screening for HBP in a clinical setting is more accurate if conducted according to recommended procedures: use an appropriately sized cuff; take the measurement at least 5 minutes after the patient’s arrival while he or she is seated with legs uncrossed and the cuffed arm is at the level of the heart; and record the mean of 2 separate measurements. There appears to be no real difference in the accuracy of automated vs manual sphygmomanometers.

Optimal frequency of screening varies. While the USPSTF found little evidence to support any particular overall screening frequency, it recommends annual screening for those who are 40 years of age or older and those ages 18 to 39 who are obese or overweight, are African American, or who have high-normal blood pressure (TABLE 3).¹ Screening every 3 to 5 years is recommended for individuals not in these categories.

Initial steps in treating HBP. The Task Force also commented on which medications to use when initiating HBP treatment (after lifestyle and dietary interventions). Non-African Americans should receive a thiazide diuretic, calcium channel blocker, angiotensin-converting enzyme inhibitor, or angiotensin-receptor blocker. African Americans should begin treatment with a thiazide diuretic or calcium channel blocker. These recommendations appear to have been adopted from the Eighth Joint National Committee, since the accompanying evidence report for the USPSTF’s update did not address this issue.⁵

Don't forget patient support

Patient support is key. As of June 2015, the Community Preventive Services Task Force (CPSTF) recommends self-measured blood pressure monitoring combined with additional support as a means of improving blood pressure control in those with HBP.⁴

Supportive measures include things such as patient counseling on medications and health behavior changes (eg, diet and exercise); education on HBP and blood pressure self-management; and use of secure electronic or Web-based tools such as text or e-mail reminders to measure blood pressure, show up for appointments, or communicate blood pressure readings to healthcare providers. Patients who participate in home self-measurement of blood pressure with additional support lower their systolic blood pressure, on average, 1.4 mm Hg more than those who do not.⁴

Remaining questions

The new USPSTF recommendation leaves several issues unaddressed. For one thing, the Affordable Care Act mandates that commercial health insurance plans provide services with an A or B Task Force recommendation to patients with no copayments. So does the new HBP recommendation mean payers have to make ABPM and HBPM available to patients at no charge?

Up to 30% of individuals diagnosed with high BP in a clinical setting will have BP in the normal range when measurements are taken outside of the doctor's office.

There are other questions, too. If HBP detected by OMBP is not confirmed when ABPM is performed, should ABPM be repeated, and if so, at what interval? What is the role of emerging technologies that use devices other than arm cuffs to measure blood pressure?

Despite these uncertainties, the new USPSTF and CPSTF recommendations refine the longstanding in-office–only approach to diagnosing and monitoring HBP and advocate newer technologies that could help improve diagnostic accuracy, avoid over-diagnosis and over-treatment, and improve patient adherence to treatment goals.

Case

A 45-year-old woman was admitted with choledocholithiasis. Two days prior, following endoscopic retrograde cholangiopancreatography (ERCP), she had gone to the OR for cholecystectomy. The procedure was completed laparoscopically, though the surgeon reported a difficult dissection. The surgeon left a Blake drain in the gallbladder fossa, which initially contained punch-colored fluid. Today, there is bilious fluid in the drain.

Overview

Surgical drains are used to monitor for postoperative leaks or abscesses, to collect normal physiologic fluid, or to minimize dead space. A hospitalist caring for surgical patients may be the first provider to note when something changes in the color or volume of surgical drains. Table 1 lists various types of drains with their indications for use.

Surgical Tubes and Drains

Chest tubes. Chest tubes are placed in the pleural space to evacuate air or fluid. They can be as thin as 20 French or as thick as 40 French (for adults). Chest tubes are typically placed between the fourth and fifth intercostal spaces in the anterior axillary or mid-axillary line; however, the location may vary according to the indication for placement. The tubes can be straight or angled.

The tubes are connected to a collecting system with a three-way chamber. The water chamber holds a column of water, which prevents air from being sucked into the pleural space with inhalation. The suction chamber can be attached to continuous wall suction to remove air or fluid, or it can be placed on “water seal” with no active suction mechanism. The third chamber is the collection chamber for fluid drainage.

Indications for a chest tube include pneumothorax, hemothorax, or a persistent or large pleural effusion. Pneumothorax and hemothorax usually require immediate chest tube placement. Chest tubes are also commonly placed at the end of thoracic surgeries to allow for appropriate re-expansion of the lung tissue.

A chest X-ray should be obtained after any chest tube insertion to ensure appropriate placement. Chest tubes are equipped with a radiopaque line along the longitudinal axis, which should be visible on X-ray. Respiratory variation in the fluid in the collecting tube, called “tidling,” should also be seen in a correctly placed chest tube, and should be monitored at the bedside to reassure continued appropriate location. The interventional radiologist or surgeon who placed the tube should determine the subsequent frequency of serial chest X-rays required to monitor the location of the chest tube.

If the patient has a pneumothorax, air bubbles will be visible in the water chamber; called an air leak, these are often more apparent when the patient coughs. The chest tube should initially be set to continuous suction at -20 mmHg to evacuate the air. Once the air leak has stopped, the chest tube should be placed on water seal to confirm resolution of the pneumothorax (water seal mimics normal physiology). If, after the transition from suction to water seal, resumption of the air leak is noted, it may indicate recurrence of the patient’s pneumothorax. A stat chest X-ray should be obtained, and the chest tube should be placed back on continuous suction. In general, a chest X-ray should be obtained any time the chest tube is changed from suction to water seal or vice versa.

If the patient experiences ongoing or worsening pain, fever, or inadequate drainage, a chest computed tomographic (CT) scan may be warranted to identify inappropriate positioning or other complications, such as occlusion or effusion of the tube. Blood or other debris might clog chest tubes; the surgical team may be able to evacuate the tube with suction tubing at the bedside. If unsuccessful, the tube may need to be removed and reinserted.

The team that placed the tube should help the hospitalist determine the timing of the chest tube removal. If the patient has a pleural effusion, the chest tube can usually be removed when the output is less than 100-200 mL per day and the lung is expanded. The tube should usually be taken off suction and placed on water seal to rule out pneumothorax prior to tube removal.

Penrose drains. Penrose drains are often used to drain fluid or to keep a space open for drainage. Surgeons may use sutures to anchor Penrose drains to skin. Common indications include:

• Ventral hernia repair;
• Debridement of infected pancreatitis; and
• Drainage of superficial abscess cavities.

Penrose drains are simple, flexible tubes that are open at both ends; in contrast to closed drains, they permit ingress as well as egress, facilitating colonization.

Closed suction drains. Closed suction drains with a plastic bulb attachment (i.e., Jackson-Pratt, Blake, Hemovac) are used to collect fluid from a postoperative cavity. Common indications include:

• Post-mastectomy to drain subcutaneous fluid;
• Abdominal surgery;
• Plastic surgery to prevent seroma formation and promote tissue apposition;
• Cholecystectomy if there is concern for damage to ducts of Luschka or other source of bile leak;
• Inadvertent postoperative leakage following a difficult rectal anastomosis; and
• Post-pancreatic surgery.

The quality and quantity of fluid drained should always be carefully noted and recorded. Changes in the fluid can imply development of bleed, leak, or other complications. The surgical team should be contacted immediately if changes are noted.

Typically, closed suction drains will be left in place until the drainage is less than 20 mL per day. These drains can be left in for weeks if necessary and will often be removed during the patient’s scheduled surgical follow-up. Rare complications include erosion into surrounding tissues and inadvertent suturing of the drain in place, such that reexploration is required to remove it. If a closed suction drain becomes occluded, contact the team that placed the drain for further recommendations on adjustment, replacement, or removal.

Nasogastric and duodenal tubes. Nasogastric tubes (NGTs) are often used in the nonoperative management of small bowel obstruction or ileus. They should be placed in the most dependent portion of the gastric lumen and confirmed by chest or abdominal X-ray. NGTs are sump pumps and have a double lumen, which includes an air port to assure flow. The air port should be patent for optimal functioning. The tube may be connected to continuous wall suction or intermittent suction, set to low (less than 60 mmHg) to avoid mucosal avulsion.

NGT output should decrease during the resolution of obstruction or ileus, and symptoms of nausea, vomiting, and abdominal distention should concomitantly improve. Persistently high output in a patient with other indicators of bowel function (flatus, for example) may suggest postpyloric placement (and placement should be checked by X-ray). The timing of NGT removal depends on resumption of bowel function.

Gastrostomy and jejunostomy tubes. Gastrostomy tubes are most commonly used for feeding but may also be used for decompression of functional or anatomic gastric outlet obstruction. They are indicated when patients need prolonged enteral access, such as those with prolonged mechanical ventilation or head and neck pathology that prohibits oral feeding. They are also rarely used for gastropexy to tack an atonic or patulous stomach to the abdominal wall or to prevent recurrence of paraesophageal hernias. These tubes can be placed percutaneously by interventional radiologists, endoscopically by surgeons and gastroenterologists, or laparoscopically or laparotomally by surgeons. This last option is often reserved for patients with difficult anatomy or those who are having laparotomy for another reason.

Because of the stomach’s generous lumen, gastrostomy tubes rarely clog. In the event that they do get clogged, carbonated liquids, meat tenderizer, or enzymes can help dissolve the obstruction. If a gastrostomy tube is left to drain, the patient may experience significant fluid and electrolyte losses, so these need to be carefully monitored.

Jejunostomy tubes are used exclusively for feeding and are usually placed 10-20 cm distal to the ligament of Treitz. These tubes are indicated in patients who require distal feedings due to gastric dysfunction or in those who have undergone a surgery in which a proximal anastomosis requires time to heal. These tubes are more apt to clog and can be more difficult to manage because the lumen of the small bowel is smaller than the stomach. Some prefer not to put pills down the tube to mitigate this risk. Routine flushes with water or saline (30 mL every four to six hours) are also helpful in mitigating the risk of clogging. In the event that they do get clogged, they may be treated like gastrostomy tubes, using carbonated liquids, meat tenderizer, or enzymes to help dissolve the obstruction.

Percutaneous tube sites should be examined frequently for signs of infection. Though gastrostomy and jejunostomy tubes are typically well secured intraabdominally, they can become dislodged. If a gastrostomy or jejunostomy tube has been in place for more than two weeks, it can easily be replaced at the bedside with a tube of comparable caliber by a member of the surgical team or by an experienced hospitalist. If the tube has been in place less than two weeks, it requires replacement with radiographic guidance, as the risk of creating a false lumen is high. Over time, tubes can become loose and fall out. If they need replacement, the preceding guidelines apply.

Back to the Case

A potential major complication of cholecystectomy is severance of the common bile duct, which necessitates significant further surgery. Less severe complications include injuries to the cholecystohepatic ducts (otherwise known as the ducts of Luschka), which can result in leakage of bile into the peritoneal cavity. A bile leak can lead to abscess and systemic infection if left undrained.

Surgeons who are concerned for such a complication intraoperatively may opt to leave a closed suction drain in the gallbladder fossa, such as a Blake drain, for monitoring and subsequent drainage. The drain will remain in place at least until the patient’s diet has been advanced fully, because digestion promotes the secretion of bile and may elucidate a leak. Bilious fluid in the Blake drain is suspicious for a leak.

The surgeon should be notified, and imaging should be obtained to find the nature of the injury to the biliary tree (CT scan with IV contrast, hepatobiliary iminodiacetic acid scan, or endoscopic retrograde cholangiopancreatography). If injury to major biliary structures (the cystic duct stump, the hepatic ducts, or the common bile duct) is diagnosed, a stent may be placed in order to restore ductile continuity.

Minor leaks, with damage to the cystic duct stump, hepatic ducts, and common bile duct ruled out, more often resolve on their own over time, and thus the patient’s closed suction drain will be left in place until biliary drainage ceases, without further initial intervention.

Bottom Line

Surgical tubes and drains have several placement indications. Alterations in quality and quantity of output can indicate changes in clinical status, and hospitalists should be able to handle initial troubleshooting. TH

Dr. Columbus is a general surgery resident at Brigham and Women’s Hospital in Boston. Dr. Havens is an instructor for the department of surgery at Brigham and Women’s Hospital. Dr. Peetz is an instructor for the department of surgery at University Hospital Case Medical Center in Cleveland.

Case

A 45-year-old woman was admitted with choledocholithiasis. Two days prior, following endoscopic retrograde cholangiopancreatography (ERCP), she had gone to the OR for cholecystectomy. The procedure was completed laparoscopically, though the surgeon reported a difficult dissection. The surgeon left a Blake drain in the gallbladder fossa, which initially contained punch-colored fluid. Today, there is bilious fluid in the drain.

Overview

Surgical drains are used to monitor for postoperative leaks or abscesses, to collect normal physiologic fluid, or to minimize dead space. A hospitalist caring for surgical patients may be the first provider to note when something changes in the color or volume of surgical drains. Table 1 lists various types of drains with their indications for use.

Surgical Tubes and Drains

Chest tubes. Chest tubes are placed in the pleural space to evacuate air or fluid. They can be as thin as 20 French or as thick as 40 French (for adults). Chest tubes are typically placed between the fourth and fifth intercostal spaces in the anterior axillary or mid-axillary line; however, the location may vary according to the indication for placement. The tubes can be straight or angled.

The tubes are connected to a collecting system with a three-way chamber. The water chamber holds a column of water, which prevents air from being sucked into the pleural space with inhalation. The suction chamber can be attached to continuous wall suction to remove air or fluid, or it can be placed on “water seal” with no active suction mechanism. The third chamber is the collection chamber for fluid drainage.

Indications for a chest tube include pneumothorax, hemothorax, or a persistent or large pleural effusion. Pneumothorax and hemothorax usually require immediate chest tube placement. Chest tubes are also commonly placed at the end of thoracic surgeries to allow for appropriate re-expansion of the lung tissue.

A chest X-ray should be obtained after any chest tube insertion to ensure appropriate placement. Chest tubes are equipped with a radiopaque line along the longitudinal axis, which should be visible on X-ray. Respiratory variation in the fluid in the collecting tube, called “tidling,” should also be seen in a correctly placed chest tube, and should be monitored at the bedside to reassure continued appropriate location. The interventional radiologist or surgeon who placed the tube should determine the subsequent frequency of serial chest X-rays required to monitor the location of the chest tube.

If the patient has a pneumothorax, air bubbles will be visible in the water chamber; called an air leak, these are often more apparent when the patient coughs. The chest tube should initially be set to continuous suction at -20 mmHg to evacuate the air. Once the air leak has stopped, the chest tube should be placed on water seal to confirm resolution of the pneumothorax (water seal mimics normal physiology). If, after the transition from suction to water seal, resumption of the air leak is noted, it may indicate recurrence of the patient’s pneumothorax. A stat chest X-ray should be obtained, and the chest tube should be placed back on continuous suction. In general, a chest X-ray should be obtained any time the chest tube is changed from suction to water seal or vice versa.

If the patient experiences ongoing or worsening pain, fever, or inadequate drainage, a chest computed tomographic (CT) scan may be warranted to identify inappropriate positioning or other complications, such as occlusion or effusion of the tube. Blood or other debris might clog chest tubes; the surgical team may be able to evacuate the tube with suction tubing at the bedside. If unsuccessful, the tube may need to be removed and reinserted.

The team that placed the tube should help the hospitalist determine the timing of the chest tube removal. If the patient has a pleural effusion, the chest tube can usually be removed when the output is less than 100-200 mL per day and the lung is expanded. The tube should usually be taken off suction and placed on water seal to rule out pneumothorax prior to tube removal.

Penrose drains. Penrose drains are often used to drain fluid or to keep a space open for drainage. Surgeons may use sutures to anchor Penrose drains to skin. Common indications include:

• Ventral hernia repair;
• Debridement of infected pancreatitis; and
• Drainage of superficial abscess cavities.

Penrose drains are simple, flexible tubes that are open at both ends; in contrast to closed drains, they permit ingress as well as egress, facilitating colonization.

Closed suction drains. Closed suction drains with a plastic bulb attachment (i.e., Jackson-Pratt, Blake, Hemovac) are used to collect fluid from a postoperative cavity. Common indications include:

• Post-mastectomy to drain subcutaneous fluid;
• Abdominal surgery;
• Plastic surgery to prevent seroma formation and promote tissue apposition;
• Cholecystectomy if there is concern for damage to ducts of Luschka or other source of bile leak;
• Inadvertent postoperative leakage following a difficult rectal anastomosis; and
• Post-pancreatic surgery.

The quality and quantity of fluid drained should always be carefully noted and recorded. Changes in the fluid can imply development of bleed, leak, or other complications. The surgical team should be contacted immediately if changes are noted.

Typically, closed suction drains will be left in place until the drainage is less than 20 mL per day. These drains can be left in for weeks if necessary and will often be removed during the patient’s scheduled surgical follow-up. Rare complications include erosion into surrounding tissues and inadvertent suturing of the drain in place, such that reexploration is required to remove it. If a closed suction drain becomes occluded, contact the team that placed the drain for further recommendations on adjustment, replacement, or removal.

Nasogastric and duodenal tubes. Nasogastric tubes (NGTs) are often used in the nonoperative management of small bowel obstruction or ileus. They should be placed in the most dependent portion of the gastric lumen and confirmed by chest or abdominal X-ray. NGTs are sump pumps and have a double lumen, which includes an air port to assure flow. The air port should be patent for optimal functioning. The tube may be connected to continuous wall suction or intermittent suction, set to low (less than 60 mmHg) to avoid mucosal avulsion.

NGT output should decrease during the resolution of obstruction or ileus, and symptoms of nausea, vomiting, and abdominal distention should concomitantly improve. Persistently high output in a patient with other indicators of bowel function (flatus, for example) may suggest postpyloric placement (and placement should be checked by X-ray). The timing of NGT removal depends on resumption of bowel function.

Gastrostomy and jejunostomy tubes. Gastrostomy tubes are most commonly used for feeding but may also be used for decompression of functional or anatomic gastric outlet obstruction. They are indicated when patients need prolonged enteral access, such as those with prolonged mechanical ventilation or head and neck pathology that prohibits oral feeding. They are also rarely used for gastropexy to tack an atonic or patulous stomach to the abdominal wall or to prevent recurrence of paraesophageal hernias. These tubes can be placed percutaneously by interventional radiologists, endoscopically by surgeons and gastroenterologists, or laparoscopically or laparotomally by surgeons. This last option is often reserved for patients with difficult anatomy or those who are having laparotomy for another reason.

Because of the stomach’s generous lumen, gastrostomy tubes rarely clog. In the event that they do get clogged, carbonated liquids, meat tenderizer, or enzymes can help dissolve the obstruction. If a gastrostomy tube is left to drain, the patient may experience significant fluid and electrolyte losses, so these need to be carefully monitored.

Jejunostomy tubes are used exclusively for feeding and are usually placed 10-20 cm distal to the ligament of Treitz. These tubes are indicated in patients who require distal feedings due to gastric dysfunction or in those who have undergone a surgery in which a proximal anastomosis requires time to heal. These tubes are more apt to clog and can be more difficult to manage because the lumen of the small bowel is smaller than the stomach. Some prefer not to put pills down the tube to mitigate this risk. Routine flushes with water or saline (30 mL every four to six hours) are also helpful in mitigating the risk of clogging. In the event that they do get clogged, they may be treated like gastrostomy tubes, using carbonated liquids, meat tenderizer, or enzymes to help dissolve the obstruction.

Percutaneous tube sites should be examined frequently for signs of infection. Though gastrostomy and jejunostomy tubes are typically well secured intraabdominally, they can become dislodged. If a gastrostomy or jejunostomy tube has been in place for more than two weeks, it can easily be replaced at the bedside with a tube of comparable caliber by a member of the surgical team or by an experienced hospitalist. If the tube has been in place less than two weeks, it requires replacement with radiographic guidance, as the risk of creating a false lumen is high. Over time, tubes can become loose and fall out. If they need replacement, the preceding guidelines apply.

Back to the Case

A potential major complication of cholecystectomy is severance of the common bile duct, which necessitates significant further surgery. Less severe complications include injuries to the cholecystohepatic ducts (otherwise known as the ducts of Luschka), which can result in leakage of bile into the peritoneal cavity. A bile leak can lead to abscess and systemic infection if left undrained.

Surgeons who are concerned for such a complication intraoperatively may opt to leave a closed suction drain in the gallbladder fossa, such as a Blake drain, for monitoring and subsequent drainage. The drain will remain in place at least until the patient’s diet has been advanced fully, because digestion promotes the secretion of bile and may elucidate a leak. Bilious fluid in the Blake drain is suspicious for a leak.

The surgeon should be notified, and imaging should be obtained to find the nature of the injury to the biliary tree (CT scan with IV contrast, hepatobiliary iminodiacetic acid scan, or endoscopic retrograde cholangiopancreatography). If injury to major biliary structures (the cystic duct stump, the hepatic ducts, or the common bile duct) is diagnosed, a stent may be placed in order to restore ductile continuity.

Minor leaks, with damage to the cystic duct stump, hepatic ducts, and common bile duct ruled out, more often resolve on their own over time, and thus the patient’s closed suction drain will be left in place until biliary drainage ceases, without further initial intervention.

Bottom Line

Surgical tubes and drains have several placement indications. Alterations in quality and quantity of output can indicate changes in clinical status, and hospitalists should be able to handle initial troubleshooting. TH

Dr. Columbus is a general surgery resident at Brigham and Women’s Hospital in Boston. Dr. Havens is an instructor for the department of surgery at Brigham and Women’s Hospital. Dr. Peetz is an instructor for the department of surgery at University Hospital Case Medical Center in Cleveland.

Case

A 45-year-old woman was admitted with choledocholithiasis. Two days prior, following endoscopic retrograde cholangiopancreatography (ERCP), she had gone to the OR for cholecystectomy. The procedure was completed laparoscopically, though the surgeon reported a difficult dissection. The surgeon left a Blake drain in the gallbladder fossa, which initially contained punch-colored fluid. Today, there is bilious fluid in the drain.

Overview

Surgical drains are used to monitor for postoperative leaks or abscesses, to collect normal physiologic fluid, or to minimize dead space. A hospitalist caring for surgical patients may be the first provider to note when something changes in the color or volume of surgical drains. Table 1 lists various types of drains with their indications for use.

Surgical Tubes and Drains

Chest tubes. Chest tubes are placed in the pleural space to evacuate air or fluid. They can be as thin as 20 French or as thick as 40 French (for adults). Chest tubes are typically placed between the fourth and fifth intercostal spaces in the anterior axillary or mid-axillary line; however, the location may vary according to the indication for placement. The tubes can be straight or angled.

The tubes are connected to a collecting system with a three-way chamber. The water chamber holds a column of water, which prevents air from being sucked into the pleural space with inhalation. The suction chamber can be attached to continuous wall suction to remove air or fluid, or it can be placed on “water seal” with no active suction mechanism. The third chamber is the collection chamber for fluid drainage.

Indications for a chest tube include pneumothorax, hemothorax, or a persistent or large pleural effusion. Pneumothorax and hemothorax usually require immediate chest tube placement. Chest tubes are also commonly placed at the end of thoracic surgeries to allow for appropriate re-expansion of the lung tissue.

A chest X-ray should be obtained after any chest tube insertion to ensure appropriate placement. Chest tubes are equipped with a radiopaque line along the longitudinal axis, which should be visible on X-ray. Respiratory variation in the fluid in the collecting tube, called “tidling,” should also be seen in a correctly placed chest tube, and should be monitored at the bedside to reassure continued appropriate location. The interventional radiologist or surgeon who placed the tube should determine the subsequent frequency of serial chest X-rays required to monitor the location of the chest tube.

If the patient has a pneumothorax, air bubbles will be visible in the water chamber; called an air leak, these are often more apparent when the patient coughs. The chest tube should initially be set to continuous suction at -20 mmHg to evacuate the air. Once the air leak has stopped, the chest tube should be placed on water seal to confirm resolution of the pneumothorax (water seal mimics normal physiology). If, after the transition from suction to water seal, resumption of the air leak is noted, it may indicate recurrence of the patient’s pneumothorax. A stat chest X-ray should be obtained, and the chest tube should be placed back on continuous suction. In general, a chest X-ray should be obtained any time the chest tube is changed from suction to water seal or vice versa.

If the patient experiences ongoing or worsening pain, fever, or inadequate drainage, a chest computed tomographic (CT) scan may be warranted to identify inappropriate positioning or other complications, such as occlusion or effusion of the tube. Blood or other debris might clog chest tubes; the surgical team may be able to evacuate the tube with suction tubing at the bedside. If unsuccessful, the tube may need to be removed and reinserted.

The team that placed the tube should help the hospitalist determine the timing of the chest tube removal. If the patient has a pleural effusion, the chest tube can usually be removed when the output is less than 100-200 mL per day and the lung is expanded. The tube should usually be taken off suction and placed on water seal to rule out pneumothorax prior to tube removal.

Penrose drains. Penrose drains are often used to drain fluid or to keep a space open for drainage. Surgeons may use sutures to anchor Penrose drains to skin. Common indications include:

• Ventral hernia repair;
• Debridement of infected pancreatitis; and
• Drainage of superficial abscess cavities.

Penrose drains are simple, flexible tubes that are open at both ends; in contrast to closed drains, they permit ingress as well as egress, facilitating colonization.

Closed suction drains. Closed suction drains with a plastic bulb attachment (i.e., Jackson-Pratt, Blake, Hemovac) are used to collect fluid from a postoperative cavity. Common indications include:

• Post-mastectomy to drain subcutaneous fluid;
• Abdominal surgery;
• Plastic surgery to prevent seroma formation and promote tissue apposition;
• Cholecystectomy if there is concern for damage to ducts of Luschka or other source of bile leak;
• Inadvertent postoperative leakage following a difficult rectal anastomosis; and
• Post-pancreatic surgery.

The quality and quantity of fluid drained should always be carefully noted and recorded. Changes in the fluid can imply development of bleed, leak, or other complications. The surgical team should be contacted immediately if changes are noted.

Typically, closed suction drains will be left in place until the drainage is less than 20 mL per day. These drains can be left in for weeks if necessary and will often be removed during the patient’s scheduled surgical follow-up. Rare complications include erosion into surrounding tissues and inadvertent suturing of the drain in place, such that reexploration is required to remove it. If a closed suction drain becomes occluded, contact the team that placed the drain for further recommendations on adjustment, replacement, or removal.

Nasogastric and duodenal tubes. Nasogastric tubes (NGTs) are often used in the nonoperative management of small bowel obstruction or ileus. They should be placed in the most dependent portion of the gastric lumen and confirmed by chest or abdominal X-ray. NGTs are sump pumps and have a double lumen, which includes an air port to assure flow. The air port should be patent for optimal functioning. The tube may be connected to continuous wall suction or intermittent suction, set to low (less than 60 mmHg) to avoid mucosal avulsion.

NGT output should decrease during the resolution of obstruction or ileus, and symptoms of nausea, vomiting, and abdominal distention should concomitantly improve. Persistently high output in a patient with other indicators of bowel function (flatus, for example) may suggest postpyloric placement (and placement should be checked by X-ray). The timing of NGT removal depends on resumption of bowel function.

Gastrostomy and jejunostomy tubes. Gastrostomy tubes are most commonly used for feeding but may also be used for decompression of functional or anatomic gastric outlet obstruction. They are indicated when patients need prolonged enteral access, such as those with prolonged mechanical ventilation or head and neck pathology that prohibits oral feeding. They are also rarely used for gastropexy to tack an atonic or patulous stomach to the abdominal wall or to prevent recurrence of paraesophageal hernias. These tubes can be placed percutaneously by interventional radiologists, endoscopically by surgeons and gastroenterologists, or laparoscopically or laparotomally by surgeons. This last option is often reserved for patients with difficult anatomy or those who are having laparotomy for another reason.

Because of the stomach’s generous lumen, gastrostomy tubes rarely clog. In the event that they do get clogged, carbonated liquids, meat tenderizer, or enzymes can help dissolve the obstruction. If a gastrostomy tube is left to drain, the patient may experience significant fluid and electrolyte losses, so these need to be carefully monitored.

Jejunostomy tubes are used exclusively for feeding and are usually placed 10-20 cm distal to the ligament of Treitz. These tubes are indicated in patients who require distal feedings due to gastric dysfunction or in those who have undergone a surgery in which a proximal anastomosis requires time to heal. These tubes are more apt to clog and can be more difficult to manage because the lumen of the small bowel is smaller than the stomach. Some prefer not to put pills down the tube to mitigate this risk. Routine flushes with water or saline (30 mL every four to six hours) are also helpful in mitigating the risk of clogging. In the event that they do get clogged, they may be treated like gastrostomy tubes, using carbonated liquids, meat tenderizer, or enzymes to help dissolve the obstruction.

Percutaneous tube sites should be examined frequently for signs of infection. Though gastrostomy and jejunostomy tubes are typically well secured intraabdominally, they can become dislodged. If a gastrostomy or jejunostomy tube has been in place for more than two weeks, it can easily be replaced at the bedside with a tube of comparable caliber by a member of the surgical team or by an experienced hospitalist. If the tube has been in place less than two weeks, it requires replacement with radiographic guidance, as the risk of creating a false lumen is high. Over time, tubes can become loose and fall out. If they need replacement, the preceding guidelines apply.

Back to the Case

A potential major complication of cholecystectomy is severance of the common bile duct, which necessitates significant further surgery. Less severe complications include injuries to the cholecystohepatic ducts (otherwise known as the ducts of Luschka), which can result in leakage of bile into the peritoneal cavity. A bile leak can lead to abscess and systemic infection if left undrained.

Surgeons who are concerned for such a complication intraoperatively may opt to leave a closed suction drain in the gallbladder fossa, such as a Blake drain, for monitoring and subsequent drainage. The drain will remain in place at least until the patient’s diet has been advanced fully, because digestion promotes the secretion of bile and may elucidate a leak. Bilious fluid in the Blake drain is suspicious for a leak.

The surgeon should be notified, and imaging should be obtained to find the nature of the injury to the biliary tree (CT scan with IV contrast, hepatobiliary iminodiacetic acid scan, or endoscopic retrograde cholangiopancreatography). If injury to major biliary structures (the cystic duct stump, the hepatic ducts, or the common bile duct) is diagnosed, a stent may be placed in order to restore ductile continuity.

Minor leaks, with damage to the cystic duct stump, hepatic ducts, and common bile duct ruled out, more often resolve on their own over time, and thus the patient’s closed suction drain will be left in place until biliary drainage ceases, without further initial intervention.

Bottom Line

Surgical tubes and drains have several placement indications. Alterations in quality and quantity of output can indicate changes in clinical status, and hospitalists should be able to handle initial troubleshooting. TH

Dr. Columbus is a general surgery resident at Brigham and Women’s Hospital in Boston. Dr. Havens is an instructor for the department of surgery at Brigham and Women’s Hospital. Dr. Peetz is an instructor for the department of surgery at University Hospital Case Medical Center in Cleveland.

ORLANDO – The one-two punch of combining the programmed cell death-1 (PD-1) inhibitor pembrolizumab with the immunomodulatory drug lenalidomide and low-dose dexamethasone produced responses in 76% of 17 heavily pretreated patients with relapsed or refractory multiple myeloma in the KEYNOTE-023 study.

This included four very good partial responses (24%) and nine partial responses (53%).

In nine lenalidomide-refractory patients, the overall response rate was 56%, including two very good partial responses (22%) and three partial responses (33%).

The efficacy results are preliminary, but support the continued development of pembrolizumab (Keytruda) in patients with multiple myeloma, Dr. Jesús San Miguel of Clinica Universidad de Navarra, Pamplona, Spain, said at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

He closed his presentation with two illustrative cases highlighting a rapid response lasting more than a year and a half in a 49-year-old man with myeloma triple-refractory to autologous stem cell transplant (ASCT), lenalidomide (Revlimid), and dexamethasone.

The second case involved a patient with double-refractory myeloma and extramedullary disease who achieved a stringent complete response after two cycles of fourth-line pembrolizumab that was associated with a “striking” reduction in lesion volume on computed tomography scans, he said.

The median duration of response among the 17 evaluable patients was 9.7 months.

The median time to first response was 1.2 months (range 1.0 months to 6.5 months). But some patients require more time and, interestingly, the quality of the response was upgraded in 11% with continued treatment, Dr. San Miguel said.

The rationale for combining PD-1 inhibitors with immunomodulatory drugs (IMiD) lies in recent research showing that lenalidomide reduces PD-ligand 1 and PD-1 expression on multiple myeloma cells as well as on T and myeloid-derived suppressor cells, he explained. In addition, lenalidomide enhances checkpoint blockade–induced effector cytokine production in multiple myeloma bone marrow and induces cytotoxicity against myeloma cells.

“Lenalidomide will increase the number of T cells and the T-cell activation and anti-PD-1 will release the brake in order to allow these activated T cells to interact with the tumor,” Dr. San Miguel said.

Patients enrolled in KEYSTONE-023 were heavily pretreated, with 26% previously exposed to pomalidomide, 76% refractory to lenalidomide, 80% refractory to their last line of therapy, and 86% having undergone prior ASCT. Half the patients were double, triple, or quadruple refractory, he noted.

The study (Abstract 505) was designed to identify the maximum tolerated dose (MTD) of pembrolizumab and to assess its safety and tolerability when given with lenalidomide and dexamethasone in patients with multiple myeloma failing at least two prior lines of therapy including a proteasome inhibitor and an IMiD. Their median age was 62 years; 64% were male.

In the dose-determination stage, three of six patients treated with pembrolizumab 2 mg/kg plus lenalidomide 25 mg and dexamethasone 40 mg experienced dose-limiting toxicities that resolved without treatment discontinuation.

After dose adjustments, a “flat dose” of pembrolizumab 200 mg given every other week in a rapid 30-minute intravenous infusion without premedication with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg weekly did not cause any dose-limiting toxicities and was identified as the final MTD, Dr. San Miguel said.

The regimen is to continue for 24 months or until tumor progression or excessive side effects and was carried forward into the dose-expansion stage in 33 additional patients with a median follow-up of 48 days.

Among all 50 patients evaluable for safety, 72% experienced at least one treatment-related adverse event of any grade and 46% (23/50 patients) had grade 3/4 adverse events including neutropenia (22%), thrombocytopenia and anemia (8% each), hyperglycemia (6%), and fatigue, muscle spasms, and diarrhea (2% each).

The adverse events were consistent with the individual drug safety profiles, but “the incidence may be underestimated due to the limited drug exposure,” Dr. San Miguel cautioned.

Immune-mediated adverse events included two cases each of hyper- and hypothyroidism, one case of thyroiditis, and one grade 2 adrenal insufficiency. No cases of colitis or pneumonitis were reported. No dose modifications or treatment discontinuations were required to mange the immune-related side effects, he said. No treatment-related deaths occurred.

In a second study reported during the same oral myeloma session, pneumonitis cropped up in 10% of heavily pretreated patients with relapsed multiple myeloma receiving a slightly different regimen of pembrolizumab plus the IMiD pomalidomide (Pomalyst) and dexamethasone. The overall response rate in the phase II study was 60% among 27 evaluable patients and 55% in those double-refractory to IMiDs and proteasome inhibitors.

[email protected]

ORLANDO – The one-two punch of combining the programmed cell death-1 (PD-1) inhibitor pembrolizumab with the immunomodulatory drug lenalidomide and low-dose dexamethasone produced responses in 76% of 17 heavily pretreated patients with relapsed or refractory multiple myeloma in the KEYNOTE-023 study.

This included four very good partial responses (24%) and nine partial responses (53%).

In nine lenalidomide-refractory patients, the overall response rate was 56%, including two very good partial responses (22%) and three partial responses (33%).

The efficacy results are preliminary, but support the continued development of pembrolizumab (Keytruda) in patients with multiple myeloma, Dr. Jesús San Miguel of Clinica Universidad de Navarra, Pamplona, Spain, said at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

He closed his presentation with two illustrative cases highlighting a rapid response lasting more than a year and a half in a 49-year-old man with myeloma triple-refractory to autologous stem cell transplant (ASCT), lenalidomide (Revlimid), and dexamethasone.

The second case involved a patient with double-refractory myeloma and extramedullary disease who achieved a stringent complete response after two cycles of fourth-line pembrolizumab that was associated with a “striking” reduction in lesion volume on computed tomography scans, he said.

The median duration of response among the 17 evaluable patients was 9.7 months.

The median time to first response was 1.2 months (range 1.0 months to 6.5 months). But some patients require more time and, interestingly, the quality of the response was upgraded in 11% with continued treatment, Dr. San Miguel said.

The rationale for combining PD-1 inhibitors with immunomodulatory drugs (IMiD) lies in recent research showing that lenalidomide reduces PD-ligand 1 and PD-1 expression on multiple myeloma cells as well as on T and myeloid-derived suppressor cells, he explained. In addition, lenalidomide enhances checkpoint blockade–induced effector cytokine production in multiple myeloma bone marrow and induces cytotoxicity against myeloma cells.

“Lenalidomide will increase the number of T cells and the T-cell activation and anti-PD-1 will release the brake in order to allow these activated T cells to interact with the tumor,” Dr. San Miguel said.

Patients enrolled in KEYSTONE-023 were heavily pretreated, with 26% previously exposed to pomalidomide, 76% refractory to lenalidomide, 80% refractory to their last line of therapy, and 86% having undergone prior ASCT. Half the patients were double, triple, or quadruple refractory, he noted.

The study (Abstract 505) was designed to identify the maximum tolerated dose (MTD) of pembrolizumab and to assess its safety and tolerability when given with lenalidomide and dexamethasone in patients with multiple myeloma failing at least two prior lines of therapy including a proteasome inhibitor and an IMiD. Their median age was 62 years; 64% were male.

In the dose-determination stage, three of six patients treated with pembrolizumab 2 mg/kg plus lenalidomide 25 mg and dexamethasone 40 mg experienced dose-limiting toxicities that resolved without treatment discontinuation.

After dose adjustments, a “flat dose” of pembrolizumab 200 mg given every other week in a rapid 30-minute intravenous infusion without premedication with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg weekly did not cause any dose-limiting toxicities and was identified as the final MTD, Dr. San Miguel said.

The regimen is to continue for 24 months or until tumor progression or excessive side effects and was carried forward into the dose-expansion stage in 33 additional patients with a median follow-up of 48 days.

Among all 50 patients evaluable for safety, 72% experienced at least one treatment-related adverse event of any grade and 46% (23/50 patients) had grade 3/4 adverse events including neutropenia (22%), thrombocytopenia and anemia (8% each), hyperglycemia (6%), and fatigue, muscle spasms, and diarrhea (2% each).

The adverse events were consistent with the individual drug safety profiles, but “the incidence may be underestimated due to the limited drug exposure,” Dr. San Miguel cautioned.

Immune-mediated adverse events included two cases each of hyper- and hypothyroidism, one case of thyroiditis, and one grade 2 adrenal insufficiency. No cases of colitis or pneumonitis were reported. No dose modifications or treatment discontinuations were required to mange the immune-related side effects, he said. No treatment-related deaths occurred.

In a second study reported during the same oral myeloma session, pneumonitis cropped up in 10% of heavily pretreated patients with relapsed multiple myeloma receiving a slightly different regimen of pembrolizumab plus the IMiD pomalidomide (Pomalyst) and dexamethasone. The overall response rate in the phase II study was 60% among 27 evaluable patients and 55% in those double-refractory to IMiDs and proteasome inhibitors.

[email protected]

ORLANDO – The one-two punch of combining the programmed cell death-1 (PD-1) inhibitor pembrolizumab with the immunomodulatory drug lenalidomide and low-dose dexamethasone produced responses in 76% of 17 heavily pretreated patients with relapsed or refractory multiple myeloma in the KEYNOTE-023 study.

This included four very good partial responses (24%) and nine partial responses (53%).

In nine lenalidomide-refractory patients, the overall response rate was 56%, including two very good partial responses (22%) and three partial responses (33%).

The efficacy results are preliminary, but support the continued development of pembrolizumab (Keytruda) in patients with multiple myeloma, Dr. Jesús San Miguel of Clinica Universidad de Navarra, Pamplona, Spain, said at the annual meeting of the American Society of Hematology.

Patrice Wendling/Frontline Medical News

He closed his presentation with two illustrative cases highlighting a rapid response lasting more than a year and a half in a 49-year-old man with myeloma triple-refractory to autologous stem cell transplant (ASCT), lenalidomide (Revlimid), and dexamethasone.

The second case involved a patient with double-refractory myeloma and extramedullary disease who achieved a stringent complete response after two cycles of fourth-line pembrolizumab that was associated with a “striking” reduction in lesion volume on computed tomography scans, he said.

The median duration of response among the 17 evaluable patients was 9.7 months.

The median time to first response was 1.2 months (range 1.0 months to 6.5 months). But some patients require more time and, interestingly, the quality of the response was upgraded in 11% with continued treatment, Dr. San Miguel said.

The rationale for combining PD-1 inhibitors with immunomodulatory drugs (IMiD) lies in recent research showing that lenalidomide reduces PD-ligand 1 and PD-1 expression on multiple myeloma cells as well as on T and myeloid-derived suppressor cells, he explained. In addition, lenalidomide enhances checkpoint blockade–induced effector cytokine production in multiple myeloma bone marrow and induces cytotoxicity against myeloma cells.

“Lenalidomide will increase the number of T cells and the T-cell activation and anti-PD-1 will release the brake in order to allow these activated T cells to interact with the tumor,” Dr. San Miguel said.

Patients enrolled in KEYSTONE-023 were heavily pretreated, with 26% previously exposed to pomalidomide, 76% refractory to lenalidomide, 80% refractory to their last line of therapy, and 86% having undergone prior ASCT. Half the patients were double, triple, or quadruple refractory, he noted.

The study (Abstract 505) was designed to identify the maximum tolerated dose (MTD) of pembrolizumab and to assess its safety and tolerability when given with lenalidomide and dexamethasone in patients with multiple myeloma failing at least two prior lines of therapy including a proteasome inhibitor and an IMiD. Their median age was 62 years; 64% were male.

In the dose-determination stage, three of six patients treated with pembrolizumab 2 mg/kg plus lenalidomide 25 mg and dexamethasone 40 mg experienced dose-limiting toxicities that resolved without treatment discontinuation.

After dose adjustments, a “flat dose” of pembrolizumab 200 mg given every other week in a rapid 30-minute intravenous infusion without premedication with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg weekly did not cause any dose-limiting toxicities and was identified as the final MTD, Dr. San Miguel said.

The regimen is to continue for 24 months or until tumor progression or excessive side effects and was carried forward into the dose-expansion stage in 33 additional patients with a median follow-up of 48 days.

Among all 50 patients evaluable for safety, 72% experienced at least one treatment-related adverse event of any grade and 46% (23/50 patients) had grade 3/4 adverse events including neutropenia (22%), thrombocytopenia and anemia (8% each), hyperglycemia (6%), and fatigue, muscle spasms, and diarrhea (2% each).

The adverse events were consistent with the individual drug safety profiles, but “the incidence may be underestimated due to the limited drug exposure,” Dr. San Miguel cautioned.

Immune-mediated adverse events included two cases each of hyper- and hypothyroidism, one case of thyroiditis, and one grade 2 adrenal insufficiency. No cases of colitis or pneumonitis were reported. No dose modifications or treatment discontinuations were required to mange the immune-related side effects, he said. No treatment-related deaths occurred.

In a second study reported during the same oral myeloma session, pneumonitis cropped up in 10% of heavily pretreated patients with relapsed multiple myeloma receiving a slightly different regimen of pembrolizumab plus the IMiD pomalidomide (Pomalyst) and dexamethasone. The overall response rate in the phase II study was 60% among 27 evaluable patients and 55% in those double-refractory to IMiDs and proteasome inhibitors.

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An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.

An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.

An expert panel has developed a communication framework to improve treatment of older, seriously ill patients who have surgical emergencies, which has been published online in Annals of Surgery.

A substantial portion of older patients who undergo emergency surgeries already have serious life-limiting illnesses such as cardiopulmonary disease, renal failure, liver failure, dementia, severe neurological impairment, or malignancy. The advisory panel based its work on the premise that surgery in these circumstances can lead to significant further morbidity, health care utilization, functional decline, prolonged hospital stay or institutionalization, and death, with attendant physical discomfort and psychological distress at the end of these patients’ lives.

Surgeons consulted in the emergency setting for these patients are hampered by patients unable to communicate well because they are in extremis, by surrogates who are unprepared for their role, and by time constraints, lack of familiarity with the patient, poor understanding of the illness by patients and families, prognostic uncertainty, and inadequate advance care planning. In addition, “many surgeons lack skills to engage in conversations about end-of-life care, or are too unfamiliar with palliative options to discuss them well,” or feel obligated to maintain postoperative life support despite the patient’s wishes, said Dr. Zara Cooper, of Ariadne Labs and the Center for Surgery and Public Health at Brigham and Women’s Hospital, both in Boston, and her associates.

To address these issues and assist surgeons in caring for such patients, an expert panel of 23 national leaders in acute care surgery, general surgery, surgical oncology, palliative medicine, critical care, emergency medicine, anesthesia, and health care innovation was convened at Harvard Medical School, Boston.

The focus of the panel’s recommendations was a structured communications framework prototype to facilitate shared decision-making in these difficult circumstances.

Among the panel’s recommendations for surgeons were the following priorities:

• Review the medical record and consult the treatment team to fully understand the patient’s current condition, comorbidities, expected illness trajectory, and preferences for end-of-life care.

• Assess functional performance as part of the routine history and physical to fully understand the patient’s fitness for surgery.

• Formulate a prognosis regarding the patient’s overall health both with and without surgery.

The panel offered a set of principles and specific elements for the meeting with the patient and family:

• The surgeon should begin by introducing himself or herself; according to reports in the literature, physicians fail to do this approximately half of the time.

• Pay attention to nonverbal communication, such as eye contact and physical contact, as this is critical to building rapport. Immediately address pain, anxiety, and other indicators of distress, to maximize the patients’ and the families’ engagement in subsequent medical discussions. “Although adequate analgesia may render a patient unable to make their own decisions, surrogates are more likely to make appropriate decisions when they feel their loved one is comfortable,” the panel noted.

• Allow pauses and silences to occur. Let the patient and the family process information and their own emotions.

• Elicit the patients’ or the surrogates’ understanding of the illness and their views of the patients’ likely trajectory, correcting any inaccuracies. This substantially influences their decisions regarding the aggressiveness of subsequent treatments.

• Inform the patient and family of the life-threatening nature of the patient’s acute condition and its potential impact on the rest of his or her life, including the possibility of prolonged life support, ICU stay, burdensome treatment, and loss of independence. Use accepted techniques for breaking bad news, and check to be sure the patient understands what was conveyed.

• At this point, the surgeon should synthesize and summarize the information from the patient, the family, and the medical record, then pause to give them time to process the information and to assess their emotional state. It is helpful to label and respond to the patient’s emotions at this juncture, and to build empathy with statements such as “I know this is difficult news, and I wish it were different.”

• Describe the benefits, burdens, and range of likely outcomes if surgery is undertaken and if it is not. The surgeon should use nonmedical language to describe symptoms, and should convey his or her expectations regarding length of hospitalization, need for and duration of life support, burdensome symptoms, discharge to an institution, and functional recovery.

• Surgeons should be able to communicate palliative options possible either in combination with surgery or instead of surgery. Palliative care can aid in managing advanced symptoms, providing psychosocial support for patients and caregivers, facilitating interdisciplinary communication, and facilitating medical decisions and care transitions.

• Avoid describing surgical procedures as “doing everything” and palliative care as “doing nothing.” This can make patients and families “feel abandoned, fearful, isolated, and angry, and fails to encompass palliative care’s practices of proactive communication, aggressive symptom management, and timely emotional support to alleviate suffering and affirm quality of life,” the panel said.

• Surgeons should explicitly support the patients’ medical decisions, whether or not they choose surgery.

The panel also cited a few factors that would assist surgeons in following these recommendations. First, surgeons must recognize the importance of communicating well with seriously ill older patients and acknowledge that this is a crucial clinical skill for them to cultivate. They must also recognize that palliative care is vital to delivering high-quality surgical care. Surgeons should consider discharging patients to hospice, which can improve pain and symptom management, improve patient and family satisfaction with care, and avoid unwanted hospitalization or cardiopulmonary resuscitation.

“There are a number of major barriers to introducing palliative care in these situations. One is an education problem - the perception on the part of patients and clinicians, and surgeons in particular, that palliative care is only limited to end-of-life care, which it is not. It is a misperception of what palliative care means in this equation - that palliative care and hospice are the same thing, which they absolutely are not,”said Dr. Cooper in an interview.

”The definition of palliative care has evolved over the past decade and the focus of palliative care is on quality of life and alleviating symptoms. End-of-life palliative care is part of that, and as patients get closer to the end of life, symptom management and quality of life become more focal than life-prolonging treatment... But for patients with chronic and serious illness, there has to be a role for palliative care because we know that when patients feel better, they tend to live longer. And when patients feel their emotional concerns and physical needs are being addressed, they tend to do better. Patients families have improved satisfaction when their loved one receives palliative care,” she noted.”

However, the number of palliative providers is completely inadequate to meet the needs of the number of seriously ill patients, she said. And a lot of hospital-based palliative care is by necessity limited to end-of-life care because of a lack of palliative resources.

Dr. Atul Gawande, a coauthor of the panel recommendations, wrote a best-selling book, Being Mortal (New York: Metropolitan Books, 2014) addressing the shortcomings and potential remaking of medical care in the context of age-related frailty, grave illness, and death. Dr. Cooper noted that there is a growing sentiment among the general public that they want to have their quality of life addressed in the type of medical care they receive. She said that Dr. Gawande’s book tapped into the perception of a lack of recognition of personhood of seriously ill patients.

“We often focus on diagnosis and we don’t have the ‘bandwidth’ to focus on the person carrying that diagnosis, and our patients and focus on the person carrying that diagnosis, but our patients and their families are demanding different types of care. So, ultimately, the patients will be the ones to push us to do better for them.”

The next steps to further developing a widely used and validated communication framework would be to create educational opportunities for clinicians to develop clinical skills in communication with seriously ill patients and palliative care, and to study the impact of these initiatives on improving outcomes most relevant to older patient. This work was supported by the Ariadne Labs, a Joint Center for Health System Innovation at Brigham and Women’s Hospital. Dr. Cooper and her associates reported having no relevant financial disclosures.