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Legislators question price of leukemia drug
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A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information. 
Photo from Business Wire
A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information.
Photo from Business Wire
A pair of US legislators are questioning why ARIAD Pharmaceuticals, Inc. has increased the price of its leukemia drug Iclusig (ponatinib) by more than $80,000 over the last several years.
ARIAD raised the price of Iclusig 4 times in 2016. The drug now costs nearly $199,000 a year.
Senator Bernie Sanders (Vermont) and Congressman Elijah Cummings (Maryland) sent a letter to ARIAD last week requesting information about these price increases.
Cummings and Sanders are also investigating whether ARIAD took additional steps to boost profits by discontinuing sales of certain dosages and quantities of Iclusig in order to charge patients and insurers more in exchange for less medicine.
“These outrageous sales tactics indicate that ARIAD is more concerned with its profit than with its patients,” Sanders and Cummings wrote in the letter.
The US Food and Drug Administration (FDA) approved Iclusig in December 2012 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).
In late 2013, the FDA suspended sales and clinical trials of the drug due to reports of serious adverse events.
The FDA allowed ARIAD to resume selling Iclusig in December 2013, but only to CML/ALL patients who cannot tolerate, or whose disease is resistant to, other tyrosine kinase inhibitors.
“Despite this new evidence showing the drug posed a far greater safety risk to patients than was known when the drug came on the market, ARIAD nonetheless raised the price of Iclusig several times over the subsequent 4 years,” Sanders and Cummings wrote.
“In the interest of patients and taxpayers, we are interested in learning more about the impact that the escalating price and restrictions on product availability have had.”
ARIAD has released a statement acknowledging Cummings’ and Sanders’ letter and defending its decisions to increase the price of Iclusig.
The company said it “makes significant investments in research and development (R&D) to advance breakthrough treatments” for patients with rare cancers.
In fact, ARIAD has invested more than $1.3 billion in R&D and accumulated losses of approximately $1.4 billion, which have not been recovered. In 2015, ARIAD generated $119 million in total revenue and invested $171 million in R&D.
The company said it intends to respond to Cummings’ and Sanders’ request for information.
COPD: Diagnostic and Treatment Update for the Primary Care Setting
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Smokers’ hand grip strength predicts risk for respiratory events
LOS ANGELES – Hand grip strength is independently predictive of risk for respiratory events in smokers who have or are at risk for chronic obstructive pulmonary disease, results from a single-center study showed.
“Measures of lung function, including spirometry, are used as the main descriptors of COPD severity and prognosis,” Carlos H. Martinez, MD, MPH, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “These measurements, as important as they are, need to be improved, in order to develop better risk and prognostic models of the disease, to identify subgroups at higher risk of poor outcomes ... With our work, we have proved that simple physical tests could be part of future prognostic models.”
Interest has grown in developing multidimensional models to predict respiratory prognosis. Such models include BODE (body mass index, airflow obstruction, dyspnea and exercise capacity), ADO (age, dyspnea and airflow obstruction), and DOSE (dyspnea, airflow obstruction, smoking status, and exacerbation frequency).
In patients with or at risk for COPD, Dr. Martinez, of the University of Michigan Health System, Ann Arbor, and his colleagues tested the associations of hand grip strength with measures of body composition such as pectoralis muscle area and extent of subcutaneous fat, imaging phenotypes, and lung function.
The researchers obtained demographic, clinical, lung function, hand grip strength, and imaging data from 441 smokers with and without COPD participating in the Genetic Epidemiology of COPD Study (COPDGene) at the National Jewish Health in Denver. Imaging methods used in the study were developed by George R. Washko, MD, and his associates at Brigham and Women’s Hospital, Boston, to evaluate patients’ body composition, including chest CTs to obtain measures of airway thickness, emphysema percentage, pectoralis muscle area, and subcutaneous adipose tissue area.
Correlations between measures of lung function, imaging phenotypes, body composition, and hand grip strength were analyzed in univariate analysis and in multivariate linear models. The association between hand grip strength and exacerbations was analyzed at enrollment and during an average follow-up of 2.6 years.
Hand grip strength was similar across groups categorized by spirometry severity and was not associated with emphysema severity.
After adjustment for demographics, smoking history, smoking intensity, comorbidities and lung imaging phenotypes, however, grip strength was associated with pectoralis muscle area (increase of 3.9 kg per one standard deviation of pectoral muscle area) and subcutaneous adipose tissue (a decrement of 5.1 kg per one standard deviation of subcutaneous adipose tissue). These associations were independent of body mass index and the presence of emphysema.
During follow-up, hand grip strength was associated with exacerbations (risk ratio 0.94 per one kg increment on grip strength) and incident exacerbations (incident risk ratio 0.92 per one kg increment on grip strength) in models adjusted for other factors known to be associated with exacerbations.
Research in body composition has mostly relied on dual absorptiometry and bioelectrical impedance, tools not routinely used in clinical practice, Dr. Martinez said. “We were surprised by the ability to show similar results using imaging data that are available from regular chest CTs.”
“We have confirmed prior hypotheses that it is not just weight or BMI that matters (to risk of exacerbations), but how much muscle and how much fat are contributing to our patient’s high or low BMI,” Dr. Martinez said.
Hand grip testing can be challenging in this patient population, he said. Still, “asking relevant questions about (patients’) physical fitness will help us to understand better our patients’ needs. We can also give more attention to the extrapulmonary structures included in the numerous chest CT scans that we order for our patients. These imaging studies, besides the information that they provide about parenchymal and mediastinal structures, include important and easy to discover clues to identify patients at higher risk of exacerbations – those with low muscle and low hand grip could benefit from close follow-up.”
Dr. Martinez acknowledged certain limitations of the study, including the selection of the measures of body composition. “We used analysis of chest CTs, instead of the gold standard of dual absorptiometry (DXA) or other methods such as bioelectrical impedance,” he said. “A final limitation is that we tested a selected group of participants in a cohort study, not a representative sample of the population, [with a] low burden of emphysema and fewer African American participants.”
Dr. Martinez disclosed that his work is supported by the National Institutes of Health and that COPDGene also receives NIH funding. He acknowledged the support and effort of all COPDGene investigators and participants.
LOS ANGELES – Hand grip strength is independently predictive of risk for respiratory events in smokers who have or are at risk for chronic obstructive pulmonary disease, results from a single-center study showed.
“Measures of lung function, including spirometry, are used as the main descriptors of COPD severity and prognosis,” Carlos H. Martinez, MD, MPH, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “These measurements, as important as they are, need to be improved, in order to develop better risk and prognostic models of the disease, to identify subgroups at higher risk of poor outcomes ... With our work, we have proved that simple physical tests could be part of future prognostic models.”
Interest has grown in developing multidimensional models to predict respiratory prognosis. Such models include BODE (body mass index, airflow obstruction, dyspnea and exercise capacity), ADO (age, dyspnea and airflow obstruction), and DOSE (dyspnea, airflow obstruction, smoking status, and exacerbation frequency).
In patients with or at risk for COPD, Dr. Martinez, of the University of Michigan Health System, Ann Arbor, and his colleagues tested the associations of hand grip strength with measures of body composition such as pectoralis muscle area and extent of subcutaneous fat, imaging phenotypes, and lung function.
The researchers obtained demographic, clinical, lung function, hand grip strength, and imaging data from 441 smokers with and without COPD participating in the Genetic Epidemiology of COPD Study (COPDGene) at the National Jewish Health in Denver. Imaging methods used in the study were developed by George R. Washko, MD, and his associates at Brigham and Women’s Hospital, Boston, to evaluate patients’ body composition, including chest CTs to obtain measures of airway thickness, emphysema percentage, pectoralis muscle area, and subcutaneous adipose tissue area.
Correlations between measures of lung function, imaging phenotypes, body composition, and hand grip strength were analyzed in univariate analysis and in multivariate linear models. The association between hand grip strength and exacerbations was analyzed at enrollment and during an average follow-up of 2.6 years.
Hand grip strength was similar across groups categorized by spirometry severity and was not associated with emphysema severity.
After adjustment for demographics, smoking history, smoking intensity, comorbidities and lung imaging phenotypes, however, grip strength was associated with pectoralis muscle area (increase of 3.9 kg per one standard deviation of pectoral muscle area) and subcutaneous adipose tissue (a decrement of 5.1 kg per one standard deviation of subcutaneous adipose tissue). These associations were independent of body mass index and the presence of emphysema.
During follow-up, hand grip strength was associated with exacerbations (risk ratio 0.94 per one kg increment on grip strength) and incident exacerbations (incident risk ratio 0.92 per one kg increment on grip strength) in models adjusted for other factors known to be associated with exacerbations.
Research in body composition has mostly relied on dual absorptiometry and bioelectrical impedance, tools not routinely used in clinical practice, Dr. Martinez said. “We were surprised by the ability to show similar results using imaging data that are available from regular chest CTs.”
“We have confirmed prior hypotheses that it is not just weight or BMI that matters (to risk of exacerbations), but how much muscle and how much fat are contributing to our patient’s high or low BMI,” Dr. Martinez said.
Hand grip testing can be challenging in this patient population, he said. Still, “asking relevant questions about (patients’) physical fitness will help us to understand better our patients’ needs. We can also give more attention to the extrapulmonary structures included in the numerous chest CT scans that we order for our patients. These imaging studies, besides the information that they provide about parenchymal and mediastinal structures, include important and easy to discover clues to identify patients at higher risk of exacerbations – those with low muscle and low hand grip could benefit from close follow-up.”
Dr. Martinez acknowledged certain limitations of the study, including the selection of the measures of body composition. “We used analysis of chest CTs, instead of the gold standard of dual absorptiometry (DXA) or other methods such as bioelectrical impedance,” he said. “A final limitation is that we tested a selected group of participants in a cohort study, not a representative sample of the population, [with a] low burden of emphysema and fewer African American participants.”
Dr. Martinez disclosed that his work is supported by the National Institutes of Health and that COPDGene also receives NIH funding. He acknowledged the support and effort of all COPDGene investigators and participants.
LOS ANGELES – Hand grip strength is independently predictive of risk for respiratory events in smokers who have or are at risk for chronic obstructive pulmonary disease, results from a single-center study showed.
“Measures of lung function, including spirometry, are used as the main descriptors of COPD severity and prognosis,” Carlos H. Martinez, MD, MPH, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “These measurements, as important as they are, need to be improved, in order to develop better risk and prognostic models of the disease, to identify subgroups at higher risk of poor outcomes ... With our work, we have proved that simple physical tests could be part of future prognostic models.”
Interest has grown in developing multidimensional models to predict respiratory prognosis. Such models include BODE (body mass index, airflow obstruction, dyspnea and exercise capacity), ADO (age, dyspnea and airflow obstruction), and DOSE (dyspnea, airflow obstruction, smoking status, and exacerbation frequency).
In patients with or at risk for COPD, Dr. Martinez, of the University of Michigan Health System, Ann Arbor, and his colleagues tested the associations of hand grip strength with measures of body composition such as pectoralis muscle area and extent of subcutaneous fat, imaging phenotypes, and lung function.
The researchers obtained demographic, clinical, lung function, hand grip strength, and imaging data from 441 smokers with and without COPD participating in the Genetic Epidemiology of COPD Study (COPDGene) at the National Jewish Health in Denver. Imaging methods used in the study were developed by George R. Washko, MD, and his associates at Brigham and Women’s Hospital, Boston, to evaluate patients’ body composition, including chest CTs to obtain measures of airway thickness, emphysema percentage, pectoralis muscle area, and subcutaneous adipose tissue area.
Correlations between measures of lung function, imaging phenotypes, body composition, and hand grip strength were analyzed in univariate analysis and in multivariate linear models. The association between hand grip strength and exacerbations was analyzed at enrollment and during an average follow-up of 2.6 years.
Hand grip strength was similar across groups categorized by spirometry severity and was not associated with emphysema severity.
After adjustment for demographics, smoking history, smoking intensity, comorbidities and lung imaging phenotypes, however, grip strength was associated with pectoralis muscle area (increase of 3.9 kg per one standard deviation of pectoral muscle area) and subcutaneous adipose tissue (a decrement of 5.1 kg per one standard deviation of subcutaneous adipose tissue). These associations were independent of body mass index and the presence of emphysema.
During follow-up, hand grip strength was associated with exacerbations (risk ratio 0.94 per one kg increment on grip strength) and incident exacerbations (incident risk ratio 0.92 per one kg increment on grip strength) in models adjusted for other factors known to be associated with exacerbations.
Research in body composition has mostly relied on dual absorptiometry and bioelectrical impedance, tools not routinely used in clinical practice, Dr. Martinez said. “We were surprised by the ability to show similar results using imaging data that are available from regular chest CTs.”
“We have confirmed prior hypotheses that it is not just weight or BMI that matters (to risk of exacerbations), but how much muscle and how much fat are contributing to our patient’s high or low BMI,” Dr. Martinez said.
Hand grip testing can be challenging in this patient population, he said. Still, “asking relevant questions about (patients’) physical fitness will help us to understand better our patients’ needs. We can also give more attention to the extrapulmonary structures included in the numerous chest CT scans that we order for our patients. These imaging studies, besides the information that they provide about parenchymal and mediastinal structures, include important and easy to discover clues to identify patients at higher risk of exacerbations – those with low muscle and low hand grip could benefit from close follow-up.”
Dr. Martinez acknowledged certain limitations of the study, including the selection of the measures of body composition. “We used analysis of chest CTs, instead of the gold standard of dual absorptiometry (DXA) or other methods such as bioelectrical impedance,” he said. “A final limitation is that we tested a selected group of participants in a cohort study, not a representative sample of the population, [with a] low burden of emphysema and fewer African American participants.”
Dr. Martinez disclosed that his work is supported by the National Institutes of Health and that COPDGene also receives NIH funding. He acknowledged the support and effort of all COPDGene investigators and participants.
AT CHEST 2016
Key clinical point:
Major finding: During an average follow-up of 2.6 years, hand grip strength was associated with cross-sectional exacerbations (risk ratio 0.94 per one kg increment on grip strength) and incident exacerbations (incident risk ratio 0.92 per one kg increment on grip strength).
Data source: Data from 441 smokers with and without COPD participating in the Genetic Epidemiology of COPD Study (COPDGene) at National Jewish Health in Denver.
Disclosures: Dr. Martinez disclosed that his work is supported by the National Institutes of Health and that COPDGene also receives NIH funding.
LMWH best for preventing PE in patients with major trauma
WAIKOLOA, HAWAII – Venous thromboembolism prophylaxis with low molecular weight heparin (LMWH), instead of unfractionated heparin (UH), is associated with lower risk of pulmonary embolism (PE) in patients with major trauma, results from a large study have shown.
The results of the study, based on data from the American College of Surgeons (ACS) Trauma Quality Improvement Program, suggest that LMWH-based strategies for thromboprophylaxis should be preferred after major trauma.
Dr. Byrne, a general surgery resident at Sunnybrook Health Science Center, Toronto, Ontario, Canada, went on to note that LMWH is often favored because of a randomized controlled trial which showed that LMWH was associated with fewer deep vein thromboses (N Engl. J. Med. 1996;335[10]:701-7). However, significant practice variability continues to exist.
“Practitioners might favor the shorter half-life of unfractionated heparin in patients where they perceive the risk for hemorrhagic complications is high,” he said. “There’s also recent evidence to suggest that dosing may be all important and that unfractionated heparin dosed three times daily may be equivalent to low molecular weight heparin. If this is true, it might suggest that the historically higher cost of low molecular weight heparin could favor the use of unfractionated heparin.”
Furthermore, there is a is a lack of evidence comparing either agent to prevent PE, he added. “This is an important gap in our knowledge, because PE frequently occurs in the absence of an identified DVT and carries a significant risk of death. At present, it is not known how practice patterns with respect to choice of prophylaxis type influence risk of PE at the patient or hospital levels.”
Due to a lack of evidence comparing agents to prevent PE, the researchers set out to compare the effectiveness of LMWH versus UH to prevent PE in patients with major trauma who were treated at trauma centers participating in the ACS Trauma Quality Improvement Program from 2012 to 2015. They included all adults with severe injury who received LMWH or UH and excluded those who died or were discharged within five days, and those with a bleeding disorder or chronic anticoagulation. The exposure was defined as thromboprophylaxis with LMWH versus UH, and the primary outcome was PE confirmed on radiologic imaging. Potential confounders were considered, including patient baseline characteristics, anatomic and global injury severity, presenting characteristics in the emergency department, acute intracranial injuries, orthopedic injuries, early surgical interventions, and timing of prophylaxis initiation.
Dr. Byrne and his associates then used three analytic approaches in the study: a propensity score matching methodology, a multivariable logistic regression model for PE, and a center-level analysis examining the influence of LMWH utilization on hospital rates of PE.
They identified 153,474 trauma patients from 217 trauma centers. Their median age was 50 years and 67% were male. Blunt trauma was most common (89%), with a mean Injury Severity Score score of 20. LMWH was the most common type of thromboprophylaxis used (74%), and PE was diagnosed in 2,722 patients (1.8%).
Compared with patients who received LMWH, those who received UH were older and were significantly more likely to have been injured by falling (42% vs. 28%), with higher rates of severe head injuries (43% vs. 24%) and intracranial hemorrhage (38% vs. 19%). Conversely, LMWH was most favored in patients with orthopedic injuries.
After propensity score matching, patients on LMWH suffered significantly fewer PEs (1.4% vs. 2.4%; odds ratio, 0.56). This result was consistent within propensity-matched subgroups, including for patients with blunt multisystem injuries (OR, 0.60), penetrating truncal injuries (OR, 0.65), shock in the ED (OR, 0.68), isolated severe traumatic brain injury (OR, 0.49), and isolated orthopedic injuries (OR, 0.28).
Results of a sensitivity analysis in which each propensity-matched pair was matched within the same trauma center yielded similar results. Specifically, patients who received LMWH were at significantly lower risk for developing PE (OR, 0.64). “Importantly, this analysis minimized residual confounding due to differences in hospital-level processes of care, such as prophylaxis dosing or frequency, mechanical prophylaxis use, and thromboembolism screening practices,” Dr. Byrne noted.
Multivariable logistic regression also showed that patients who received LMWH had lower odds of PE (OR, 0.59). Other significant predictors of PE included obesity (OR, 1.54), severe chest injury (OR, 1.31), femoral shaft fracture (OR, 1.60), and spinal cord injury (OR, 1.60). Delays in prophylaxis initiation beyond the first day in the hospital were associated with significantly higher rates of PE, with an 80% increased risk of PE for patients who had their prophylaxis initiated after the fourth day.
The researchers conducted a center-level analysis in an effort to answer the question whether practice patterns with respect to choice of prophylaxis type influence hospital rates of PE. Across all 217 trauma centers in the study, the median rate of LMWH use was 80%, while the mean rate of PE was 1.6%. When trauma centers were grouped into quartiles based on their unique rate of LMWH use, trauma centers in the highest quartile (median LMWH use: 95%) were 50 times more likely to use LMWH, compared to those in the lowest quartile (median LMWH use: 39%) after adjusting for patient case mix. Compared with the lowest quartile, trauma centers that used the greatest proportion of LMWH had significantly lower rates of PE (1.2% vs. 2.0%). After adjusting for patient baseline and injury characteristics, patients who were treated at trauma centers in the highest quartile had significantly lower odds of PE (OR, 0.59).
Dr. Byrne acknowledged certain limitations of the study, including the potential for residual confounding and the inability to account for the dosing and frequency of prophylaxis that was given. “We were only able to measure the type and timing of prophylaxis initiation. We don’t know what doses of prophylaxis were used, and it is possible that the trauma centers included in this study favored use of UH twice daily,” he said.
Therefore, it is possible that the results might have been different if they had been able to directly compare LMWH to UH administered three times a day. “We also couldn’t measure interruptions in dosing due to surgery or patient refusal,” he said. “However, if it the case that UH is more likely to be refused based on the need for more frequent dosing, perhaps that is another feather in the cap of low molecular weight heparin-based thromboprophylaxis strategies. Larger prospective studies are needed, that take into account prophylaxis type and dosing, and are powered to detect a difference with respect to PE.”
Dr. Byrne reported having no financial disclosures.
WAIKOLOA, HAWAII – Venous thromboembolism prophylaxis with low molecular weight heparin (LMWH), instead of unfractionated heparin (UH), is associated with lower risk of pulmonary embolism (PE) in patients with major trauma, results from a large study have shown.
The results of the study, based on data from the American College of Surgeons (ACS) Trauma Quality Improvement Program, suggest that LMWH-based strategies for thromboprophylaxis should be preferred after major trauma.
Dr. Byrne, a general surgery resident at Sunnybrook Health Science Center, Toronto, Ontario, Canada, went on to note that LMWH is often favored because of a randomized controlled trial which showed that LMWH was associated with fewer deep vein thromboses (N Engl. J. Med. 1996;335[10]:701-7). However, significant practice variability continues to exist.
“Practitioners might favor the shorter half-life of unfractionated heparin in patients where they perceive the risk for hemorrhagic complications is high,” he said. “There’s also recent evidence to suggest that dosing may be all important and that unfractionated heparin dosed three times daily may be equivalent to low molecular weight heparin. If this is true, it might suggest that the historically higher cost of low molecular weight heparin could favor the use of unfractionated heparin.”
Furthermore, there is a is a lack of evidence comparing either agent to prevent PE, he added. “This is an important gap in our knowledge, because PE frequently occurs in the absence of an identified DVT and carries a significant risk of death. At present, it is not known how practice patterns with respect to choice of prophylaxis type influence risk of PE at the patient or hospital levels.”
Due to a lack of evidence comparing agents to prevent PE, the researchers set out to compare the effectiveness of LMWH versus UH to prevent PE in patients with major trauma who were treated at trauma centers participating in the ACS Trauma Quality Improvement Program from 2012 to 2015. They included all adults with severe injury who received LMWH or UH and excluded those who died or were discharged within five days, and those with a bleeding disorder or chronic anticoagulation. The exposure was defined as thromboprophylaxis with LMWH versus UH, and the primary outcome was PE confirmed on radiologic imaging. Potential confounders were considered, including patient baseline characteristics, anatomic and global injury severity, presenting characteristics in the emergency department, acute intracranial injuries, orthopedic injuries, early surgical interventions, and timing of prophylaxis initiation.
Dr. Byrne and his associates then used three analytic approaches in the study: a propensity score matching methodology, a multivariable logistic regression model for PE, and a center-level analysis examining the influence of LMWH utilization on hospital rates of PE.
They identified 153,474 trauma patients from 217 trauma centers. Their median age was 50 years and 67% were male. Blunt trauma was most common (89%), with a mean Injury Severity Score score of 20. LMWH was the most common type of thromboprophylaxis used (74%), and PE was diagnosed in 2,722 patients (1.8%).
Compared with patients who received LMWH, those who received UH were older and were significantly more likely to have been injured by falling (42% vs. 28%), with higher rates of severe head injuries (43% vs. 24%) and intracranial hemorrhage (38% vs. 19%). Conversely, LMWH was most favored in patients with orthopedic injuries.
After propensity score matching, patients on LMWH suffered significantly fewer PEs (1.4% vs. 2.4%; odds ratio, 0.56). This result was consistent within propensity-matched subgroups, including for patients with blunt multisystem injuries (OR, 0.60), penetrating truncal injuries (OR, 0.65), shock in the ED (OR, 0.68), isolated severe traumatic brain injury (OR, 0.49), and isolated orthopedic injuries (OR, 0.28).
Results of a sensitivity analysis in which each propensity-matched pair was matched within the same trauma center yielded similar results. Specifically, patients who received LMWH were at significantly lower risk for developing PE (OR, 0.64). “Importantly, this analysis minimized residual confounding due to differences in hospital-level processes of care, such as prophylaxis dosing or frequency, mechanical prophylaxis use, and thromboembolism screening practices,” Dr. Byrne noted.
Multivariable logistic regression also showed that patients who received LMWH had lower odds of PE (OR, 0.59). Other significant predictors of PE included obesity (OR, 1.54), severe chest injury (OR, 1.31), femoral shaft fracture (OR, 1.60), and spinal cord injury (OR, 1.60). Delays in prophylaxis initiation beyond the first day in the hospital were associated with significantly higher rates of PE, with an 80% increased risk of PE for patients who had their prophylaxis initiated after the fourth day.
The researchers conducted a center-level analysis in an effort to answer the question whether practice patterns with respect to choice of prophylaxis type influence hospital rates of PE. Across all 217 trauma centers in the study, the median rate of LMWH use was 80%, while the mean rate of PE was 1.6%. When trauma centers were grouped into quartiles based on their unique rate of LMWH use, trauma centers in the highest quartile (median LMWH use: 95%) were 50 times more likely to use LMWH, compared to those in the lowest quartile (median LMWH use: 39%) after adjusting for patient case mix. Compared with the lowest quartile, trauma centers that used the greatest proportion of LMWH had significantly lower rates of PE (1.2% vs. 2.0%). After adjusting for patient baseline and injury characteristics, patients who were treated at trauma centers in the highest quartile had significantly lower odds of PE (OR, 0.59).
Dr. Byrne acknowledged certain limitations of the study, including the potential for residual confounding and the inability to account for the dosing and frequency of prophylaxis that was given. “We were only able to measure the type and timing of prophylaxis initiation. We don’t know what doses of prophylaxis were used, and it is possible that the trauma centers included in this study favored use of UH twice daily,” he said.
Therefore, it is possible that the results might have been different if they had been able to directly compare LMWH to UH administered three times a day. “We also couldn’t measure interruptions in dosing due to surgery or patient refusal,” he said. “However, if it the case that UH is more likely to be refused based on the need for more frequent dosing, perhaps that is another feather in the cap of low molecular weight heparin-based thromboprophylaxis strategies. Larger prospective studies are needed, that take into account prophylaxis type and dosing, and are powered to detect a difference with respect to PE.”
Dr. Byrne reported having no financial disclosures.
WAIKOLOA, HAWAII – Venous thromboembolism prophylaxis with low molecular weight heparin (LMWH), instead of unfractionated heparin (UH), is associated with lower risk of pulmonary embolism (PE) in patients with major trauma, results from a large study have shown.
The results of the study, based on data from the American College of Surgeons (ACS) Trauma Quality Improvement Program, suggest that LMWH-based strategies for thromboprophylaxis should be preferred after major trauma.
Dr. Byrne, a general surgery resident at Sunnybrook Health Science Center, Toronto, Ontario, Canada, went on to note that LMWH is often favored because of a randomized controlled trial which showed that LMWH was associated with fewer deep vein thromboses (N Engl. J. Med. 1996;335[10]:701-7). However, significant practice variability continues to exist.
“Practitioners might favor the shorter half-life of unfractionated heparin in patients where they perceive the risk for hemorrhagic complications is high,” he said. “There’s also recent evidence to suggest that dosing may be all important and that unfractionated heparin dosed three times daily may be equivalent to low molecular weight heparin. If this is true, it might suggest that the historically higher cost of low molecular weight heparin could favor the use of unfractionated heparin.”
Furthermore, there is a is a lack of evidence comparing either agent to prevent PE, he added. “This is an important gap in our knowledge, because PE frequently occurs in the absence of an identified DVT and carries a significant risk of death. At present, it is not known how practice patterns with respect to choice of prophylaxis type influence risk of PE at the patient or hospital levels.”
Due to a lack of evidence comparing agents to prevent PE, the researchers set out to compare the effectiveness of LMWH versus UH to prevent PE in patients with major trauma who were treated at trauma centers participating in the ACS Trauma Quality Improvement Program from 2012 to 2015. They included all adults with severe injury who received LMWH or UH and excluded those who died or were discharged within five days, and those with a bleeding disorder or chronic anticoagulation. The exposure was defined as thromboprophylaxis with LMWH versus UH, and the primary outcome was PE confirmed on radiologic imaging. Potential confounders were considered, including patient baseline characteristics, anatomic and global injury severity, presenting characteristics in the emergency department, acute intracranial injuries, orthopedic injuries, early surgical interventions, and timing of prophylaxis initiation.
Dr. Byrne and his associates then used three analytic approaches in the study: a propensity score matching methodology, a multivariable logistic regression model for PE, and a center-level analysis examining the influence of LMWH utilization on hospital rates of PE.
They identified 153,474 trauma patients from 217 trauma centers. Their median age was 50 years and 67% were male. Blunt trauma was most common (89%), with a mean Injury Severity Score score of 20. LMWH was the most common type of thromboprophylaxis used (74%), and PE was diagnosed in 2,722 patients (1.8%).
Compared with patients who received LMWH, those who received UH were older and were significantly more likely to have been injured by falling (42% vs. 28%), with higher rates of severe head injuries (43% vs. 24%) and intracranial hemorrhage (38% vs. 19%). Conversely, LMWH was most favored in patients with orthopedic injuries.
After propensity score matching, patients on LMWH suffered significantly fewer PEs (1.4% vs. 2.4%; odds ratio, 0.56). This result was consistent within propensity-matched subgroups, including for patients with blunt multisystem injuries (OR, 0.60), penetrating truncal injuries (OR, 0.65), shock in the ED (OR, 0.68), isolated severe traumatic brain injury (OR, 0.49), and isolated orthopedic injuries (OR, 0.28).
Results of a sensitivity analysis in which each propensity-matched pair was matched within the same trauma center yielded similar results. Specifically, patients who received LMWH were at significantly lower risk for developing PE (OR, 0.64). “Importantly, this analysis minimized residual confounding due to differences in hospital-level processes of care, such as prophylaxis dosing or frequency, mechanical prophylaxis use, and thromboembolism screening practices,” Dr. Byrne noted.
Multivariable logistic regression also showed that patients who received LMWH had lower odds of PE (OR, 0.59). Other significant predictors of PE included obesity (OR, 1.54), severe chest injury (OR, 1.31), femoral shaft fracture (OR, 1.60), and spinal cord injury (OR, 1.60). Delays in prophylaxis initiation beyond the first day in the hospital were associated with significantly higher rates of PE, with an 80% increased risk of PE for patients who had their prophylaxis initiated after the fourth day.
The researchers conducted a center-level analysis in an effort to answer the question whether practice patterns with respect to choice of prophylaxis type influence hospital rates of PE. Across all 217 trauma centers in the study, the median rate of LMWH use was 80%, while the mean rate of PE was 1.6%. When trauma centers were grouped into quartiles based on their unique rate of LMWH use, trauma centers in the highest quartile (median LMWH use: 95%) were 50 times more likely to use LMWH, compared to those in the lowest quartile (median LMWH use: 39%) after adjusting for patient case mix. Compared with the lowest quartile, trauma centers that used the greatest proportion of LMWH had significantly lower rates of PE (1.2% vs. 2.0%). After adjusting for patient baseline and injury characteristics, patients who were treated at trauma centers in the highest quartile had significantly lower odds of PE (OR, 0.59).
Dr. Byrne acknowledged certain limitations of the study, including the potential for residual confounding and the inability to account for the dosing and frequency of prophylaxis that was given. “We were only able to measure the type and timing of prophylaxis initiation. We don’t know what doses of prophylaxis were used, and it is possible that the trauma centers included in this study favored use of UH twice daily,” he said.
Therefore, it is possible that the results might have been different if they had been able to directly compare LMWH to UH administered three times a day. “We also couldn’t measure interruptions in dosing due to surgery or patient refusal,” he said. “However, if it the case that UH is more likely to be refused based on the need for more frequent dosing, perhaps that is another feather in the cap of low molecular weight heparin-based thromboprophylaxis strategies. Larger prospective studies are needed, that take into account prophylaxis type and dosing, and are powered to detect a difference with respect to PE.”
Dr. Byrne reported having no financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point:
Major finding: After propensity score matching, patients on LMWH had significantly fewer PEs, compared with those on unfractionated heparin (1.4% vs. 2.4%; odds ratio, 0.56). Data source: A multicenter analysis of 2,722 trauma patients who were diagnosed with pulmonary embolism.
Disclosures: Dr. Byrne reported having no financial disclosures.
Chest physician perceptions of e-cigarettes mixed
AT CHEST 2016
LOS ANGELES – Chest physicians in the United States are likely to encounter electronic cigarette users in clinical practice, yet there is no consensus regarding how to advise them, results from a survey suggest.
“There is controversy in the community of physicians we surveyed on whether e-cigarettes would be useful for smoking cessation and whether they can reduce harm from tobacco smoking,” lead study author Stephen R. Baldassarri, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “Our results suggest that we need more high quality scientific data regarding potential harms and benefits of e-cigarettes in order to inform both health professionals and the general public.”
When asked if ECs promote tobacco cessation, respondents were split (33% agreed or strongly agreed while 32% disagreed or strongly disagreed); only 13% believed that ECs were at least as effective as Food and Drug Administration–approved treatments to promote smoking cessation, and 11% reported that ECs should be used in an initial quit attempt. Dr. Baldassarri also reported that 6% of respondents thought ECs are more harmful than smoking, 21% thought switching from daily tobacco smoking to EC use would improve a patient’s health, and 55% reported feeling comfortable discussing health effects of ECs with their patients.
“In light of the fact that the long-term health risks of ECs remain unknown, we were surprised to find that more than half of the survey respondents reported feeling comfortable discussing health effects of ECs,” Dr. Baldassarri commented. “This proportion was higher than we expected given the current state of the scientific evidence.”
He acknowledged certain limitations of the survey, including its low response rate, “which limits the degree to which we can generalize our findings to account for the perceptions of all chest physicians,” he said. “We surveyed providers only within CHEST, and opinions and experiences of physicians outside of the organization and in other specialties may vary. And finally, since knowledge regarding e-cigarettes is rapidly evolving, the perceptions and opinions here are likely subject to change over the next few years as more becomes known.”
Dr. Baldassarri reported having no financial disclosures.
AT CHEST 2016
LOS ANGELES – Chest physicians in the United States are likely to encounter electronic cigarette users in clinical practice, yet there is no consensus regarding how to advise them, results from a survey suggest.
“There is controversy in the community of physicians we surveyed on whether e-cigarettes would be useful for smoking cessation and whether they can reduce harm from tobacco smoking,” lead study author Stephen R. Baldassarri, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “Our results suggest that we need more high quality scientific data regarding potential harms and benefits of e-cigarettes in order to inform both health professionals and the general public.”
When asked if ECs promote tobacco cessation, respondents were split (33% agreed or strongly agreed while 32% disagreed or strongly disagreed); only 13% believed that ECs were at least as effective as Food and Drug Administration–approved treatments to promote smoking cessation, and 11% reported that ECs should be used in an initial quit attempt. Dr. Baldassarri also reported that 6% of respondents thought ECs are more harmful than smoking, 21% thought switching from daily tobacco smoking to EC use would improve a patient’s health, and 55% reported feeling comfortable discussing health effects of ECs with their patients.
“In light of the fact that the long-term health risks of ECs remain unknown, we were surprised to find that more than half of the survey respondents reported feeling comfortable discussing health effects of ECs,” Dr. Baldassarri commented. “This proportion was higher than we expected given the current state of the scientific evidence.”
He acknowledged certain limitations of the survey, including its low response rate, “which limits the degree to which we can generalize our findings to account for the perceptions of all chest physicians,” he said. “We surveyed providers only within CHEST, and opinions and experiences of physicians outside of the organization and in other specialties may vary. And finally, since knowledge regarding e-cigarettes is rapidly evolving, the perceptions and opinions here are likely subject to change over the next few years as more becomes known.”
Dr. Baldassarri reported having no financial disclosures.
AT CHEST 2016
LOS ANGELES – Chest physicians in the United States are likely to encounter electronic cigarette users in clinical practice, yet there is no consensus regarding how to advise them, results from a survey suggest.
“There is controversy in the community of physicians we surveyed on whether e-cigarettes would be useful for smoking cessation and whether they can reduce harm from tobacco smoking,” lead study author Stephen R. Baldassarri, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “Our results suggest that we need more high quality scientific data regarding potential harms and benefits of e-cigarettes in order to inform both health professionals and the general public.”
When asked if ECs promote tobacco cessation, respondents were split (33% agreed or strongly agreed while 32% disagreed or strongly disagreed); only 13% believed that ECs were at least as effective as Food and Drug Administration–approved treatments to promote smoking cessation, and 11% reported that ECs should be used in an initial quit attempt. Dr. Baldassarri also reported that 6% of respondents thought ECs are more harmful than smoking, 21% thought switching from daily tobacco smoking to EC use would improve a patient’s health, and 55% reported feeling comfortable discussing health effects of ECs with their patients.
“In light of the fact that the long-term health risks of ECs remain unknown, we were surprised to find that more than half of the survey respondents reported feeling comfortable discussing health effects of ECs,” Dr. Baldassarri commented. “This proportion was higher than we expected given the current state of the scientific evidence.”
He acknowledged certain limitations of the survey, including its low response rate, “which limits the degree to which we can generalize our findings to account for the perceptions of all chest physicians,” he said. “We surveyed providers only within CHEST, and opinions and experiences of physicians outside of the organization and in other specialties may vary. And finally, since knowledge regarding e-cigarettes is rapidly evolving, the perceptions and opinions here are likely subject to change over the next few years as more becomes known.”
Dr. Baldassarri reported having no financial disclosures.
Key clinical point:
Major finding: When asked if electronic cigarettes (ECs) promote tobacco cessation, respondents were split (33% agreed or strongly agreed, while 32% disagreed or strongly disagreed).
Data source: Responses from 994 members of the American College of Chest Physicians who completed a brief online questionnaire about practice patterns and perceptions regarding EC use and tobacco smoking among their patients.
Disclosures: Dr. Baldassarri reported having no financial disclosures.
Pelvic fracture pattern predicts the need for hemorrhage control
WAIKOLOA, HAWAII – Blunt trauma patients admitted in shock with anterior posterior compression III or vertical shear fracture patterns, or patients with open pelvic fracture are at greatest risk of severe bleeding requiring pelvic hemorrhage control intervention, results from a multicenter trial demonstrated.
Thirty years ago, researchers defined a classification of pelvic fracture based on a pattern of force applied to the pelvis, Todd W. Costantini, MD, said at the annual meeting of the American Association for the Surgery of Trauma. They identified three main force patterns, including lateral compression, anterior posterior compression, and vertical shear (Radiology. 1986 Aug;160 [2]:445-51).
In a recently published study, Dr. Costantini and his associates found wide variability in the use of various pelvic hemorrhage control methods (J Trauma Acute Care Surg. 2016 May;80 [5]:717-25). “While angioembolization alone and external fixator placement alone were the most common methods used, there were various combinations of these methods used at different times by different institutions,” he said.
These results prompted the researchers to prospectively evaluate the correlation between pelvic fracture pattern and modern care of pelvic hemorrhage control at 11 Level I trauma centers over a two year period. Inclusion criteria for the study, which was sponsored by the AAST Multi-institutional Trials Committee, were patients over the age of 18, blunt mechanism of injury, and shock on admission, which was defined as an admission systolic blood pressure of less than 90 mm Hg, or heart rate greater than 120, or base deficit greater than 5. Exclusion criteria included isolated hip fracture, pregnancy, and lack of pelvic imaging.
The researchers evaluated the pelvic fracture pattern for each patient in the study. “Each pelvic image was evaluated by a trauma surgeon, orthopedic surgeon, or radiologist and classified using the Young-Burgess Classification system,” Dr. Costantini said. Next, they used univariate and multivariate logistic regression analysis to analyze predictors for hemorrhage control intervention and mortality. The objective was to determine whether pelvic fracture pattern would predict the need for a hemorrhage control intervention.
Of the 46,716 trauma patients admitted over the two year period, 1,339 sustained a pelvic fracture. Of these, 178 met criteria for shock. The researchers excluded 15 patients due to lack of pelvic imaging, which left 163 patients in the final analysis. Their mean age was 44 years and 58% were male. On admission, their mean systolic blood pressure was 93 mm Hg, their mean heart rate was 117 beats per minute, and their median Injury Severity Score was 28. The mean hospital length of stay was 12 days and the mortality rate was 30%. The three most common mechanisms of injury were motor vehicle crash (42%), followed by pedestrian versus auto (23%), and falls (18%).
Compared with patients who did not require hemorrhage control intervention, those who did received more transfusion of packed red blood cells (13 vs. 7 units, respectively; P less than .01) and fresh frozen plasma (10 vs. 5 units; P = .01). In addition, 67% of patients with open pelvic fracture required a hemorrhage control intervention. The rate of mortality was similar between the patients who required a pelvic hemorrhage control intervention and those who did not (34% vs. 28%; P = .47).
The three most common types of pelvic fracture patterns were lateral compression I (36%) and II (23%), followed by vertical shear (13%). Patients with lateral compression I and II fractures were least likely to require hemorrhage control intervention (22% and 19%, respectively). However, on univariate analysis, patients with anterior posterior compression III fractures and those with vertical shear fractures were more likely to require a pelvic hemorrhage control intervention, compared with those who sustained other types of pelvic fractures (83% and 55%, respectively).
On multivariate analysis, the three main independent predictors of need for a hemorrhagic control intervention were anterior posterior compression III fracture (odds ratio, 109.43; P less than .001), open pelvic fracture (OR, 7.36; P = .014), and vertical shear fracture (OR, 6.99; P = .002). Pelvic fracture pattern did not predict mortality on multivariate analysis.
The invited discussant, Joseph M. Galante, MD, trauma medical director for the University of California, Davis Health System, characterized the study as important, “because it examines all forms of hemorrhage control, not just arterioembolism in the treatment of pelvic fractures,” he said. “The ability to predict who will need hemorrhage control allows for earlier mobilization to resources, both in the operating room or interventional suite and in the resuscitation bay.”
Dr. Costantini reported having no financial disclosures.
WAIKOLOA, HAWAII – Blunt trauma patients admitted in shock with anterior posterior compression III or vertical shear fracture patterns, or patients with open pelvic fracture are at greatest risk of severe bleeding requiring pelvic hemorrhage control intervention, results from a multicenter trial demonstrated.
Thirty years ago, researchers defined a classification of pelvic fracture based on a pattern of force applied to the pelvis, Todd W. Costantini, MD, said at the annual meeting of the American Association for the Surgery of Trauma. They identified three main force patterns, including lateral compression, anterior posterior compression, and vertical shear (Radiology. 1986 Aug;160 [2]:445-51).
In a recently published study, Dr. Costantini and his associates found wide variability in the use of various pelvic hemorrhage control methods (J Trauma Acute Care Surg. 2016 May;80 [5]:717-25). “While angioembolization alone and external fixator placement alone were the most common methods used, there were various combinations of these methods used at different times by different institutions,” he said.
These results prompted the researchers to prospectively evaluate the correlation between pelvic fracture pattern and modern care of pelvic hemorrhage control at 11 Level I trauma centers over a two year period. Inclusion criteria for the study, which was sponsored by the AAST Multi-institutional Trials Committee, were patients over the age of 18, blunt mechanism of injury, and shock on admission, which was defined as an admission systolic blood pressure of less than 90 mm Hg, or heart rate greater than 120, or base deficit greater than 5. Exclusion criteria included isolated hip fracture, pregnancy, and lack of pelvic imaging.
The researchers evaluated the pelvic fracture pattern for each patient in the study. “Each pelvic image was evaluated by a trauma surgeon, orthopedic surgeon, or radiologist and classified using the Young-Burgess Classification system,” Dr. Costantini said. Next, they used univariate and multivariate logistic regression analysis to analyze predictors for hemorrhage control intervention and mortality. The objective was to determine whether pelvic fracture pattern would predict the need for a hemorrhage control intervention.
Of the 46,716 trauma patients admitted over the two year period, 1,339 sustained a pelvic fracture. Of these, 178 met criteria for shock. The researchers excluded 15 patients due to lack of pelvic imaging, which left 163 patients in the final analysis. Their mean age was 44 years and 58% were male. On admission, their mean systolic blood pressure was 93 mm Hg, their mean heart rate was 117 beats per minute, and their median Injury Severity Score was 28. The mean hospital length of stay was 12 days and the mortality rate was 30%. The three most common mechanisms of injury were motor vehicle crash (42%), followed by pedestrian versus auto (23%), and falls (18%).
Compared with patients who did not require hemorrhage control intervention, those who did received more transfusion of packed red blood cells (13 vs. 7 units, respectively; P less than .01) and fresh frozen plasma (10 vs. 5 units; P = .01). In addition, 67% of patients with open pelvic fracture required a hemorrhage control intervention. The rate of mortality was similar between the patients who required a pelvic hemorrhage control intervention and those who did not (34% vs. 28%; P = .47).
The three most common types of pelvic fracture patterns were lateral compression I (36%) and II (23%), followed by vertical shear (13%). Patients with lateral compression I and II fractures were least likely to require hemorrhage control intervention (22% and 19%, respectively). However, on univariate analysis, patients with anterior posterior compression III fractures and those with vertical shear fractures were more likely to require a pelvic hemorrhage control intervention, compared with those who sustained other types of pelvic fractures (83% and 55%, respectively).
On multivariate analysis, the three main independent predictors of need for a hemorrhagic control intervention were anterior posterior compression III fracture (odds ratio, 109.43; P less than .001), open pelvic fracture (OR, 7.36; P = .014), and vertical shear fracture (OR, 6.99; P = .002). Pelvic fracture pattern did not predict mortality on multivariate analysis.
The invited discussant, Joseph M. Galante, MD, trauma medical director for the University of California, Davis Health System, characterized the study as important, “because it examines all forms of hemorrhage control, not just arterioembolism in the treatment of pelvic fractures,” he said. “The ability to predict who will need hemorrhage control allows for earlier mobilization to resources, both in the operating room or interventional suite and in the resuscitation bay.”
Dr. Costantini reported having no financial disclosures.
WAIKOLOA, HAWAII – Blunt trauma patients admitted in shock with anterior posterior compression III or vertical shear fracture patterns, or patients with open pelvic fracture are at greatest risk of severe bleeding requiring pelvic hemorrhage control intervention, results from a multicenter trial demonstrated.
Thirty years ago, researchers defined a classification of pelvic fracture based on a pattern of force applied to the pelvis, Todd W. Costantini, MD, said at the annual meeting of the American Association for the Surgery of Trauma. They identified three main force patterns, including lateral compression, anterior posterior compression, and vertical shear (Radiology. 1986 Aug;160 [2]:445-51).
In a recently published study, Dr. Costantini and his associates found wide variability in the use of various pelvic hemorrhage control methods (J Trauma Acute Care Surg. 2016 May;80 [5]:717-25). “While angioembolization alone and external fixator placement alone were the most common methods used, there were various combinations of these methods used at different times by different institutions,” he said.
These results prompted the researchers to prospectively evaluate the correlation between pelvic fracture pattern and modern care of pelvic hemorrhage control at 11 Level I trauma centers over a two year period. Inclusion criteria for the study, which was sponsored by the AAST Multi-institutional Trials Committee, were patients over the age of 18, blunt mechanism of injury, and shock on admission, which was defined as an admission systolic blood pressure of less than 90 mm Hg, or heart rate greater than 120, or base deficit greater than 5. Exclusion criteria included isolated hip fracture, pregnancy, and lack of pelvic imaging.
The researchers evaluated the pelvic fracture pattern for each patient in the study. “Each pelvic image was evaluated by a trauma surgeon, orthopedic surgeon, or radiologist and classified using the Young-Burgess Classification system,” Dr. Costantini said. Next, they used univariate and multivariate logistic regression analysis to analyze predictors for hemorrhage control intervention and mortality. The objective was to determine whether pelvic fracture pattern would predict the need for a hemorrhage control intervention.
Of the 46,716 trauma patients admitted over the two year period, 1,339 sustained a pelvic fracture. Of these, 178 met criteria for shock. The researchers excluded 15 patients due to lack of pelvic imaging, which left 163 patients in the final analysis. Their mean age was 44 years and 58% were male. On admission, their mean systolic blood pressure was 93 mm Hg, their mean heart rate was 117 beats per minute, and their median Injury Severity Score was 28. The mean hospital length of stay was 12 days and the mortality rate was 30%. The three most common mechanisms of injury were motor vehicle crash (42%), followed by pedestrian versus auto (23%), and falls (18%).
Compared with patients who did not require hemorrhage control intervention, those who did received more transfusion of packed red blood cells (13 vs. 7 units, respectively; P less than .01) and fresh frozen plasma (10 vs. 5 units; P = .01). In addition, 67% of patients with open pelvic fracture required a hemorrhage control intervention. The rate of mortality was similar between the patients who required a pelvic hemorrhage control intervention and those who did not (34% vs. 28%; P = .47).
The three most common types of pelvic fracture patterns were lateral compression I (36%) and II (23%), followed by vertical shear (13%). Patients with lateral compression I and II fractures were least likely to require hemorrhage control intervention (22% and 19%, respectively). However, on univariate analysis, patients with anterior posterior compression III fractures and those with vertical shear fractures were more likely to require a pelvic hemorrhage control intervention, compared with those who sustained other types of pelvic fractures (83% and 55%, respectively).
On multivariate analysis, the three main independent predictors of need for a hemorrhagic control intervention were anterior posterior compression III fracture (odds ratio, 109.43; P less than .001), open pelvic fracture (OR, 7.36; P = .014), and vertical shear fracture (OR, 6.99; P = .002). Pelvic fracture pattern did not predict mortality on multivariate analysis.
The invited discussant, Joseph M. Galante, MD, trauma medical director for the University of California, Davis Health System, characterized the study as important, “because it examines all forms of hemorrhage control, not just arterioembolism in the treatment of pelvic fractures,” he said. “The ability to predict who will need hemorrhage control allows for earlier mobilization to resources, both in the operating room or interventional suite and in the resuscitation bay.”
Dr. Costantini reported having no financial disclosures.
AT THE AAST ANNUAL MEETING
Key clinical point:
Major finding: On multivariate analysis, the three main independent predictors of need for a hemorrhagic control intervention were anterior posterior compression III fracture (odds ratio, 109.43; P less than .001), open pelvic fracture (OR, 7.36; P = .014), and vertical shear fracture (OR, 6.99; P = .002). Data source: A prospective evaluation of 163 patients with pelvic fracture who were admitted to 11 Level I trauma centers over a two-year period.
Disclosures: Dr. Costantini reported having no financial disclosures.
C. difficile risk linked to antibiotic use in prior hospital bed occupant
Inpatients are at increased risk for Clostridium difficile infection if the previous occupant of their hospital bed received antibiotics, according to a report published online October 10 in JAMA Internal Medicine.
The increase in risk was characterized as “modest,” but it is important because the use of antibiotics in hospitals is so common. “Our results show that antibiotics can potentially cause harm to patients who do not themselves receive the antibiotics and thus emphasize the value of antibiotic stewardship,” said Daniel E. Freedberg, MD, a gastroenterologist at Columbia University, New York, and his associates (JAMA Intern Med. 2016 Oct 10. doi: 10.1001/jamainternmed.2016.6193).
They performed a large retrospective cohort study of sequentially hospitalized adults at four New York City area hospitals between 2010 and 2015. They focused on 100,615 pairs of patients in which the first patient was hospitalized for at least 24 hours and was discharged less than 1 week before the second patient was hospitalized in the same bed for at least 48 hours. A total of 576 “second patients” developed C. difficile infection 2 to14 days after hospitalization.
There were no C. difficile outbreaks during the study period, and the incidence of C. difficile infections remained constant. The “first patient” occupied the bed for a median of 3.0 days, and the median interval before the “second patient” arrived at the bed was 10 hours. Among those who developed a C. difficile infection, the median time from admission into the bed to the development of the infection was 6.4 days.
The cumulative incidence of C. difficile infections was significantly higher among second patients when the prior bed occupants had received antibiotics (0.72%) than when the prior bed occupants had not received antibiotics (0.43%). This correlation remained strong and significant when the data were adjusted to account for potential confounders such as the second patient’s comorbidities and use of antibiotics, the number of nearby patients who already had a C. difficile infection, and the type of hospital ward involved.
The strong association also persisted through numerous sensitivity analyses, including one that excluded the 1,497 patient pairs in which the first patient had had a recent C. difficile infection (adjusted hazard ratio, 1.20). In a further analysis examining multiple risk factors for infection, receipt of antibiotics by the “first patient” was the only factor associated with subsequent patients’ infection risk. The investigators noted that the four hospitals involved in this study were among the many that routinely single out the rooms of patients with C. difficile infection for intensive cleaning, including UV radiation.
These findings “support the hypothesis that antibiotics given to one patient may alter the local microenvironment to influence a different patients’ risk” for C. difficile infection, the investigators concluded.
The study was supported in part by the American Gastroenterological Association and the National Center for Advancing Translational Sciences. Dr. Freedberg and his associates reported having no relevant financial disclosures.
Inpatients are at increased risk for Clostridium difficile infection if the previous occupant of their hospital bed received antibiotics, according to a report published online October 10 in JAMA Internal Medicine.
The increase in risk was characterized as “modest,” but it is important because the use of antibiotics in hospitals is so common. “Our results show that antibiotics can potentially cause harm to patients who do not themselves receive the antibiotics and thus emphasize the value of antibiotic stewardship,” said Daniel E. Freedberg, MD, a gastroenterologist at Columbia University, New York, and his associates (JAMA Intern Med. 2016 Oct 10. doi: 10.1001/jamainternmed.2016.6193).
They performed a large retrospective cohort study of sequentially hospitalized adults at four New York City area hospitals between 2010 and 2015. They focused on 100,615 pairs of patients in which the first patient was hospitalized for at least 24 hours and was discharged less than 1 week before the second patient was hospitalized in the same bed for at least 48 hours. A total of 576 “second patients” developed C. difficile infection 2 to14 days after hospitalization.
There were no C. difficile outbreaks during the study period, and the incidence of C. difficile infections remained constant. The “first patient” occupied the bed for a median of 3.0 days, and the median interval before the “second patient” arrived at the bed was 10 hours. Among those who developed a C. difficile infection, the median time from admission into the bed to the development of the infection was 6.4 days.
The cumulative incidence of C. difficile infections was significantly higher among second patients when the prior bed occupants had received antibiotics (0.72%) than when the prior bed occupants had not received antibiotics (0.43%). This correlation remained strong and significant when the data were adjusted to account for potential confounders such as the second patient’s comorbidities and use of antibiotics, the number of nearby patients who already had a C. difficile infection, and the type of hospital ward involved.
The strong association also persisted through numerous sensitivity analyses, including one that excluded the 1,497 patient pairs in which the first patient had had a recent C. difficile infection (adjusted hazard ratio, 1.20). In a further analysis examining multiple risk factors for infection, receipt of antibiotics by the “first patient” was the only factor associated with subsequent patients’ infection risk. The investigators noted that the four hospitals involved in this study were among the many that routinely single out the rooms of patients with C. difficile infection for intensive cleaning, including UV radiation.
These findings “support the hypothesis that antibiotics given to one patient may alter the local microenvironment to influence a different patients’ risk” for C. difficile infection, the investigators concluded.
The study was supported in part by the American Gastroenterological Association and the National Center for Advancing Translational Sciences. Dr. Freedberg and his associates reported having no relevant financial disclosures.
Inpatients are at increased risk for Clostridium difficile infection if the previous occupant of their hospital bed received antibiotics, according to a report published online October 10 in JAMA Internal Medicine.
The increase in risk was characterized as “modest,” but it is important because the use of antibiotics in hospitals is so common. “Our results show that antibiotics can potentially cause harm to patients who do not themselves receive the antibiotics and thus emphasize the value of antibiotic stewardship,” said Daniel E. Freedberg, MD, a gastroenterologist at Columbia University, New York, and his associates (JAMA Intern Med. 2016 Oct 10. doi: 10.1001/jamainternmed.2016.6193).
They performed a large retrospective cohort study of sequentially hospitalized adults at four New York City area hospitals between 2010 and 2015. They focused on 100,615 pairs of patients in which the first patient was hospitalized for at least 24 hours and was discharged less than 1 week before the second patient was hospitalized in the same bed for at least 48 hours. A total of 576 “second patients” developed C. difficile infection 2 to14 days after hospitalization.
There were no C. difficile outbreaks during the study period, and the incidence of C. difficile infections remained constant. The “first patient” occupied the bed for a median of 3.0 days, and the median interval before the “second patient” arrived at the bed was 10 hours. Among those who developed a C. difficile infection, the median time from admission into the bed to the development of the infection was 6.4 days.
The cumulative incidence of C. difficile infections was significantly higher among second patients when the prior bed occupants had received antibiotics (0.72%) than when the prior bed occupants had not received antibiotics (0.43%). This correlation remained strong and significant when the data were adjusted to account for potential confounders such as the second patient’s comorbidities and use of antibiotics, the number of nearby patients who already had a C. difficile infection, and the type of hospital ward involved.
The strong association also persisted through numerous sensitivity analyses, including one that excluded the 1,497 patient pairs in which the first patient had had a recent C. difficile infection (adjusted hazard ratio, 1.20). In a further analysis examining multiple risk factors for infection, receipt of antibiotics by the “first patient” was the only factor associated with subsequent patients’ infection risk. The investigators noted that the four hospitals involved in this study were among the many that routinely single out the rooms of patients with C. difficile infection for intensive cleaning, including UV radiation.
These findings “support the hypothesis that antibiotics given to one patient may alter the local microenvironment to influence a different patients’ risk” for C. difficile infection, the investigators concluded.
The study was supported in part by the American Gastroenterological Association and the National Center for Advancing Translational Sciences. Dr. Freedberg and his associates reported having no relevant financial disclosures.
FROM JAMA INTERNAL MEDICINE
Trading Her Stethoscope for a Script Helps Hospitalist Rana Tan, MD, Find Balance
When Rana Tan, MD, was a young child, she often played with dolls, dressing them up and inventing stories about them. Teachers would comment to Dr. Tan’s parents about her creativity and that she belonged on stage or behind the scenes, writing plays or movies. But her parents discouraged any profession relating to the arts, wanting a more respectable career for their daughter.
To some, there is nothing more respectable than medicine. After graduating medical school at the University California, Davis in 1990, Dr. Tan spent the next four years at Mercy Hospital in San Diego, completing a one-year internship, two years of residency, and another year of chief residency. Then from 1994 to 1997, she pursued a pulmonary and critical-care fellowship at the Medical College of Wisconsin.
After training for seven years, Dr. Tan worked in private practice in Bremerton, Wash., practicing pulmonary and critical-care medicine for the next eight years, and then joined Sound Physicians as a hospitalist in 2005 at Harrison Medical Center in Bremerton. Since 2010, she has served as its chief hospitalist.
Despite all of her education and training, Dr. Tan never forgot about her dolls or how much fun she had creating their life stories.
For years, much of her creativity had been bottled up and was ready to be unleashed. But how? The answer sat a few blocks away from Harrison: the Bremerton Community Theater. For the past 17 years, Dr. Tan has volunteered for the theater by performing in numerous plays, creating costumes and set designs, and directing more than a dozen plays for the youth theater program.
“As much as I enjoy my career, I don’t know if I could just do medicine,” says Dr. Tan, adding that acting demands her to explore a wide variety of emotions, which enables her to better understand and connect with her patients. “I’m incredibly fortunate that we have a community theater down the street and am afforded the opportunity to do all sorts of things that keep me balanced.”
Curtains Up
Back in 1999, Dr. Tan auditioned for Come Back to the Five and Dime, Jimmy Dean, Jimmy Dean, a 1976 play by Ed Graczyk about the reunion of childhood friends in drought-stricken Texas.
“This community theater had a very strong clique of people who acted in everything,” she says, adding that the same directors tapped the same actors for various roles. “It was very difficult to break in. I was very lucky that I was cast as Joanne in this play.”
Over the next two years, she repeatedly auditioned for various plays, but she never got so much as a thank you, let alone a callback. It seemed her acting career was over before it even started. But luck was on her side. She received an audition notice from a local director who had not volunteered at the theater for some time and didn’t have a preset agenda for casting.
“I got one of the lead parts in Rumors,” she says, referring to a Neil Simon play. “Then I was cast in more and more plays.”
Of all the roles she has performed, two are most memorable: Kate Keller in Arthur Miller’s All My Sons and Sister Aloysius in John Patrick Shanley’s Doubt: A Parable.
Dr. Tan explains that both roles spoke to her in different ways. Even though she never personally experienced the plights of the characters, she understood them, related to them, and became them on stage.
“I’m very grateful for having these two theater experiences,” she says.
Like many community theaters, Bremerton is staffed by volunteers. Out of necessity, Dr. Tan was asked to help with set design and also costuming. To boost interest in the arts and ticket sales, the theater also established a club for children between ages 6 and 18. It produced one show, but the youth program wasn’t well-organized and soon fizzled. Simultaneously, Dr. Tan wrote an adaption of Little Red Riding Hood, which revived the program and was chosen for the summer play in 2007.
Since then, she has directed 15 more plays, including Sleeping Beauty, The Little Mermaid, and A Seussified Christmas Carol. She says her favorite, however, was a spoof on the Law & Order television show called Law & Order: Fairy Tale Unit.
Confidence and Coyotes
Each play at the community theater may involve up to 50 cast members, including children.
“We have children who are incredibly shy, you can’t hear them on stage, and they run to sit next to their parents,” she says. “Sometimes, by the end of the audition process, their voices are stronger and they’re more confident because we audition in groups. By the end of the rehearsal process, they’re not clinging to their parents anymore.”
As a director, she has never yelled or raised her voice to any child actor. When she needs children to be quiet to listen to her rules or instructions, she uses a hand signal called “Quiet Coyote.” (Touch your thumb to your third and fourth fingers and raise your index finger and pinkie to resemble a coyote’s head.) She says they immediately stop talking and start listening.
One of her favorite youth theater memories happened several years ago, when one parent said that her six-year-old daughter wanted to dress up as Dr. Tan for Halloween by styling her hair in a bun, wearing glasses, and carrying a clipboard.
“Even though I may be exhausted at the end of the day, I still head straight to the theater,” Dr. Tan says, adding that her husband, Eric Spencer, a professional actor, is the theater’s technical director.
“Every heaviness that I have on my shoulders from the hospital is now gone. It resets me and puts me in a different place. For that, I will always be grateful.” TH
Carol Patton is a freelance writer in Las Vegas.
When Rana Tan, MD, was a young child, she often played with dolls, dressing them up and inventing stories about them. Teachers would comment to Dr. Tan’s parents about her creativity and that she belonged on stage or behind the scenes, writing plays or movies. But her parents discouraged any profession relating to the arts, wanting a more respectable career for their daughter.
To some, there is nothing more respectable than medicine. After graduating medical school at the University California, Davis in 1990, Dr. Tan spent the next four years at Mercy Hospital in San Diego, completing a one-year internship, two years of residency, and another year of chief residency. Then from 1994 to 1997, she pursued a pulmonary and critical-care fellowship at the Medical College of Wisconsin.
After training for seven years, Dr. Tan worked in private practice in Bremerton, Wash., practicing pulmonary and critical-care medicine for the next eight years, and then joined Sound Physicians as a hospitalist in 2005 at Harrison Medical Center in Bremerton. Since 2010, she has served as its chief hospitalist.
Despite all of her education and training, Dr. Tan never forgot about her dolls or how much fun she had creating their life stories.
For years, much of her creativity had been bottled up and was ready to be unleashed. But how? The answer sat a few blocks away from Harrison: the Bremerton Community Theater. For the past 17 years, Dr. Tan has volunteered for the theater by performing in numerous plays, creating costumes and set designs, and directing more than a dozen plays for the youth theater program.
“As much as I enjoy my career, I don’t know if I could just do medicine,” says Dr. Tan, adding that acting demands her to explore a wide variety of emotions, which enables her to better understand and connect with her patients. “I’m incredibly fortunate that we have a community theater down the street and am afforded the opportunity to do all sorts of things that keep me balanced.”
Curtains Up
Back in 1999, Dr. Tan auditioned for Come Back to the Five and Dime, Jimmy Dean, Jimmy Dean, a 1976 play by Ed Graczyk about the reunion of childhood friends in drought-stricken Texas.
“This community theater had a very strong clique of people who acted in everything,” she says, adding that the same directors tapped the same actors for various roles. “It was very difficult to break in. I was very lucky that I was cast as Joanne in this play.”
Over the next two years, she repeatedly auditioned for various plays, but she never got so much as a thank you, let alone a callback. It seemed her acting career was over before it even started. But luck was on her side. She received an audition notice from a local director who had not volunteered at the theater for some time and didn’t have a preset agenda for casting.
“I got one of the lead parts in Rumors,” she says, referring to a Neil Simon play. “Then I was cast in more and more plays.”
Of all the roles she has performed, two are most memorable: Kate Keller in Arthur Miller’s All My Sons and Sister Aloysius in John Patrick Shanley’s Doubt: A Parable.
Dr. Tan explains that both roles spoke to her in different ways. Even though she never personally experienced the plights of the characters, she understood them, related to them, and became them on stage.
“I’m very grateful for having these two theater experiences,” she says.
Like many community theaters, Bremerton is staffed by volunteers. Out of necessity, Dr. Tan was asked to help with set design and also costuming. To boost interest in the arts and ticket sales, the theater also established a club for children between ages 6 and 18. It produced one show, but the youth program wasn’t well-organized and soon fizzled. Simultaneously, Dr. Tan wrote an adaption of Little Red Riding Hood, which revived the program and was chosen for the summer play in 2007.
Since then, she has directed 15 more plays, including Sleeping Beauty, The Little Mermaid, and A Seussified Christmas Carol. She says her favorite, however, was a spoof on the Law & Order television show called Law & Order: Fairy Tale Unit.
Confidence and Coyotes
Each play at the community theater may involve up to 50 cast members, including children.
“We have children who are incredibly shy, you can’t hear them on stage, and they run to sit next to their parents,” she says. “Sometimes, by the end of the audition process, their voices are stronger and they’re more confident because we audition in groups. By the end of the rehearsal process, they’re not clinging to their parents anymore.”
As a director, she has never yelled or raised her voice to any child actor. When she needs children to be quiet to listen to her rules or instructions, she uses a hand signal called “Quiet Coyote.” (Touch your thumb to your third and fourth fingers and raise your index finger and pinkie to resemble a coyote’s head.) She says they immediately stop talking and start listening.
One of her favorite youth theater memories happened several years ago, when one parent said that her six-year-old daughter wanted to dress up as Dr. Tan for Halloween by styling her hair in a bun, wearing glasses, and carrying a clipboard.
“Even though I may be exhausted at the end of the day, I still head straight to the theater,” Dr. Tan says, adding that her husband, Eric Spencer, a professional actor, is the theater’s technical director.
“Every heaviness that I have on my shoulders from the hospital is now gone. It resets me and puts me in a different place. For that, I will always be grateful.” TH
Carol Patton is a freelance writer in Las Vegas.
When Rana Tan, MD, was a young child, she often played with dolls, dressing them up and inventing stories about them. Teachers would comment to Dr. Tan’s parents about her creativity and that she belonged on stage or behind the scenes, writing plays or movies. But her parents discouraged any profession relating to the arts, wanting a more respectable career for their daughter.
To some, there is nothing more respectable than medicine. After graduating medical school at the University California, Davis in 1990, Dr. Tan spent the next four years at Mercy Hospital in San Diego, completing a one-year internship, two years of residency, and another year of chief residency. Then from 1994 to 1997, she pursued a pulmonary and critical-care fellowship at the Medical College of Wisconsin.
After training for seven years, Dr. Tan worked in private practice in Bremerton, Wash., practicing pulmonary and critical-care medicine for the next eight years, and then joined Sound Physicians as a hospitalist in 2005 at Harrison Medical Center in Bremerton. Since 2010, she has served as its chief hospitalist.
Despite all of her education and training, Dr. Tan never forgot about her dolls or how much fun she had creating their life stories.
For years, much of her creativity had been bottled up and was ready to be unleashed. But how? The answer sat a few blocks away from Harrison: the Bremerton Community Theater. For the past 17 years, Dr. Tan has volunteered for the theater by performing in numerous plays, creating costumes and set designs, and directing more than a dozen plays for the youth theater program.
“As much as I enjoy my career, I don’t know if I could just do medicine,” says Dr. Tan, adding that acting demands her to explore a wide variety of emotions, which enables her to better understand and connect with her patients. “I’m incredibly fortunate that we have a community theater down the street and am afforded the opportunity to do all sorts of things that keep me balanced.”
Curtains Up
Back in 1999, Dr. Tan auditioned for Come Back to the Five and Dime, Jimmy Dean, Jimmy Dean, a 1976 play by Ed Graczyk about the reunion of childhood friends in drought-stricken Texas.
“This community theater had a very strong clique of people who acted in everything,” she says, adding that the same directors tapped the same actors for various roles. “It was very difficult to break in. I was very lucky that I was cast as Joanne in this play.”
Over the next two years, she repeatedly auditioned for various plays, but she never got so much as a thank you, let alone a callback. It seemed her acting career was over before it even started. But luck was on her side. She received an audition notice from a local director who had not volunteered at the theater for some time and didn’t have a preset agenda for casting.
“I got one of the lead parts in Rumors,” she says, referring to a Neil Simon play. “Then I was cast in more and more plays.”
Of all the roles she has performed, two are most memorable: Kate Keller in Arthur Miller’s All My Sons and Sister Aloysius in John Patrick Shanley’s Doubt: A Parable.
Dr. Tan explains that both roles spoke to her in different ways. Even though she never personally experienced the plights of the characters, she understood them, related to them, and became them on stage.
“I’m very grateful for having these two theater experiences,” she says.
Like many community theaters, Bremerton is staffed by volunteers. Out of necessity, Dr. Tan was asked to help with set design and also costuming. To boost interest in the arts and ticket sales, the theater also established a club for children between ages 6 and 18. It produced one show, but the youth program wasn’t well-organized and soon fizzled. Simultaneously, Dr. Tan wrote an adaption of Little Red Riding Hood, which revived the program and was chosen for the summer play in 2007.
Since then, she has directed 15 more plays, including Sleeping Beauty, The Little Mermaid, and A Seussified Christmas Carol. She says her favorite, however, was a spoof on the Law & Order television show called Law & Order: Fairy Tale Unit.
Confidence and Coyotes
Each play at the community theater may involve up to 50 cast members, including children.
“We have children who are incredibly shy, you can’t hear them on stage, and they run to sit next to their parents,” she says. “Sometimes, by the end of the audition process, their voices are stronger and they’re more confident because we audition in groups. By the end of the rehearsal process, they’re not clinging to their parents anymore.”
As a director, she has never yelled or raised her voice to any child actor. When she needs children to be quiet to listen to her rules or instructions, she uses a hand signal called “Quiet Coyote.” (Touch your thumb to your third and fourth fingers and raise your index finger and pinkie to resemble a coyote’s head.) She says they immediately stop talking and start listening.
One of her favorite youth theater memories happened several years ago, when one parent said that her six-year-old daughter wanted to dress up as Dr. Tan for Halloween by styling her hair in a bun, wearing glasses, and carrying a clipboard.
“Even though I may be exhausted at the end of the day, I still head straight to the theater,” Dr. Tan says, adding that her husband, Eric Spencer, a professional actor, is the theater’s technical director.
“Every heaviness that I have on my shoulders from the hospital is now gone. It resets me and puts me in a different place. For that, I will always be grateful.” TH
Carol Patton is a freelance writer in Las Vegas.
FDA grants drug orphan designation for GVHD
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
Photo by Linda Bartlett
The US Food and Drug Administration (FDA) has granted orphan drug designation to ALXN1007 for the treatment of acute graft-versus-host disease (GVHD).
ALXN1007 is an anti-inflammatory monoclonal antibody targeting complement protein C5a.
The drug is being developed
by Alexion Pharmaceuticals, Inc.
It is currently under investigation in a phase 2 trial of patients with acute GVHD of the lower gastrointestinal tract (GI-GVHD).
Results from this trial were presented at the 21st Congress of the European Hematology Association (abstract LB2269).
The presentation included 15 patients with newly diagnosed, biopsy-confirmed acute GI-GVHD. The patients had a median age of 60 (range, 25-69), and 60% were male.
Patients had acute myeloid leukemia/myelodysplastic syndrome (n=8), acute lymphoblastic leukemia (n=2), acute lymphocytic leukemia (n=1), acute myeloblastic leukemia (n=1), aplastic anemia (n=1), cutaneous T-cell lymphoma (n=1), and mantle cell lymphoma (n=1).
Most patients received transplants from matched, unrelated donors (n=11); 3 had matched, related donors; and 1 had a mismatched donor. Ten patients received peripheral blood grafts, 4 received cord blood, and 1 received a bone marrow transplant.
Patients had grade 1 (n=7), grade 2 (n=2), and grade 3 (n=6) acute GI-GVHD.
The patients received weekly doses of ALXN1007 at 10 mg/kg, in combination with methylprednisolone at an initial dose of 2 mg/kg, through day 56.
Thirteen patients were evaluable for efficacy. One patient experienced leukemia relapse at day 18, and 1 withdrew from the study early.
The overall acute GVHD response rate was 77% (10/13), both at day 28 and day 56. The complete GI-GVHD response rate was 69% at day 28 and 77% at day 56.
At day 180, the nonrelapse mortality rate was 12.5%, and the overall survival rate was 69.2%.
All of the patients had treatment-emergent adverse events (AEs), and 11 patients (69%) had serious treatment-emergent AEs.
Five patients experienced a total of 12 treatment-related AEs (1 case each)—adenovirus infection, bronchopulmonary aspergillosis, chills, corona virus infection, viral cystitis, Epstein-Barr virus infection, hypersensitivity, influenza, influenza-like illness, infusion-related reaction, respiratory syncytial virus infection, and tremor.
There were 6 deaths, but none were considered treatment-related.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
ALXN1007 has orphan designation from the European Commission as well.
TBI scoring system predicts outcomes with only initial head CT findings
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
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AT ACS 2016
Key clinical point:
Major finding: CCTST score was strongly associated with patient mortality (Odds ratio, 1.31), rivaling both the Glasgow Coma Score (OR, 1.14) and the Abbreviated Injury Score – Head (OR, 2.68)Data source: The retrospective database study comprised 620 head trauma patients.
Disclosures: Neither Ronnie Mubang, MD, or Stan Stawicki, MD, had financial disclosures.
