Stress levels, access to sick leave (or lack thereof), hazardous conditions, and interactions with coworkers have a ripple effect on the lives of workers, their families, and their communities. A safe workplace that supports the well-being of workers can have far-reaching benefits. That’s the premise and promise of Fundamentals of Total Worker Health Approaches: Essential Elements for Advancing Worker Safety, Health, and Well-Being, created by the National Institute for Occupational Safety and Health (NIOSH).

The workbook provides a “user-friendly entry point” into total worker health with examples and tips, such as, “design programs with a long-term outlook to ensure sustainability. Short-term approaches have short-term value.” It also includes a self-assessment tool and resources to develop an action plan and measure progress specific to the organization. A new conceptual model—a “hierarchy of controls”—lists ways to minimize or eliminate exposure to hazards in the workplace, from least effective (eg, providing personal protective equipment) to most effective (eg, physically removing the hazard).

Each workplace is unique, NIOSH says, and because the experiences of people who manage and work in them differ, the workbook is not intended as a one-size-fits-all tool. But it can be used to provide a “snapshot” of where the organization is on the path to total worker health.

Stress levels, access to sick leave (or lack thereof), hazardous conditions, and interactions with coworkers have a ripple effect on the lives of workers, their families, and their communities. A safe workplace that supports the well-being of workers can have far-reaching benefits. That’s the premise and promise of Fundamentals of Total Worker Health Approaches: Essential Elements for Advancing Worker Safety, Health, and Well-Being, created by the National Institute for Occupational Safety and Health (NIOSH).

The workbook provides a “user-friendly entry point” into total worker health with examples and tips, such as, “design programs with a long-term outlook to ensure sustainability. Short-term approaches have short-term value.” It also includes a self-assessment tool and resources to develop an action plan and measure progress specific to the organization. A new conceptual model—a “hierarchy of controls”—lists ways to minimize or eliminate exposure to hazards in the workplace, from least effective (eg, providing personal protective equipment) to most effective (eg, physically removing the hazard).

Each workplace is unique, NIOSH says, and because the experiences of people who manage and work in them differ, the workbook is not intended as a one-size-fits-all tool. But it can be used to provide a “snapshot” of where the organization is on the path to total worker health.

Stress levels, access to sick leave (or lack thereof), hazardous conditions, and interactions with coworkers have a ripple effect on the lives of workers, their families, and their communities. A safe workplace that supports the well-being of workers can have far-reaching benefits. That’s the premise and promise of Fundamentals of Total Worker Health Approaches: Essential Elements for Advancing Worker Safety, Health, and Well-Being, created by the National Institute for Occupational Safety and Health (NIOSH).

The workbook provides a “user-friendly entry point” into total worker health with examples and tips, such as, “design programs with a long-term outlook to ensure sustainability. Short-term approaches have short-term value.” It also includes a self-assessment tool and resources to develop an action plan and measure progress specific to the organization. A new conceptual model—a “hierarchy of controls”—lists ways to minimize or eliminate exposure to hazards in the workplace, from least effective (eg, providing personal protective equipment) to most effective (eg, physically removing the hazard).

Each workplace is unique, NIOSH says, and because the experiences of people who manage and work in them differ, the workbook is not intended as a one-size-fits-all tool. But it can be used to provide a “snapshot” of where the organization is on the path to total worker health.

An appeals court has struck down a Florida law that banned physicians from asking patients about firearms, ruling that the so-called gun gag law violates doctors’ First Amendment rights.

The decision by the 11th U.S. Circuit Court of Appeals enables Florida physicians to once again query patients and families about gun ownership and record firearm information in their records. The court, however, left intact a provision that allows patients to refuse answering such questions and upheld another rule that physicians cannot discriminate against patients based on firearm status.

Courtesy Marion P. Hammer

[email protected]

On Twitter @legal_med

An appeals court has struck down a Florida law that banned physicians from asking patients about firearms, ruling that the so-called gun gag law violates doctors’ First Amendment rights.

The decision by the 11th U.S. Circuit Court of Appeals enables Florida physicians to once again query patients and families about gun ownership and record firearm information in their records. The court, however, left intact a provision that allows patients to refuse answering such questions and upheld another rule that physicians cannot discriminate against patients based on firearm status.

Courtesy Marion P. Hammer

[email protected]

On Twitter @legal_med

An appeals court has struck down a Florida law that banned physicians from asking patients about firearms, ruling that the so-called gun gag law violates doctors’ First Amendment rights.

The decision by the 11th U.S. Circuit Court of Appeals enables Florida physicians to once again query patients and families about gun ownership and record firearm information in their records. The court, however, left intact a provision that allows patients to refuse answering such questions and upheld another rule that physicians cannot discriminate against patients based on firearm status.

Courtesy Marion P. Hammer

[email protected]

On Twitter @legal_med

Photo by Juan D. Alfonso

A study published in NEJM provides evidence that Zika virus RNA remain longer in blood and semen than in other body fluids, which suggests these may be superior diagnostic specimens.

This is the first study in which researchers examined multiple body fluids for the presence of Zika virus over a length of time.

The team sought to determine the frequency and duration of detectable Zika virus RNA in serum, saliva, urine, semen, and vaginal secretions.

They collected such specimens from 150 men and women in Puerto Rico who initially tested positive for Zika virus in urine or blood. The specimens were collected weekly for the first month and then at 2 months, 4 months, and 6 months.

The researchers tested all specimens using the Trioplex RT-PCR assay, a test that can be used to detect dengue, chikungunya, and Zika virus RNA. There have been allegations that this assay is less effective than a test used to detect Zika virus alone.

The researchers also performed validation analyses for the use of the Trioplex RT-PCR assay in semen. And they tested serum using the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

The US Centers for Disease Control and Prevention (CDC) developed both Zika MAC-ELISA and the Trioplex RT-PCR assay. This research was supported by the CDC.

After sample testing was complete, the researchers used parametric Weibull regression models to estimate the time to the loss of Zika virus RNA, which they reported in medians and 95th percentiles.

Results

The researchers said 88% of subjects (132/150) had detectable Zika virus RNA in at least 1 serum specimen. The median time to the loss of RNA detection in serum was 14 days (95% confidence interval [CI], 11 to 17), and the 95th percentile of time was 54 days (95% CI, 43 to 64).

The team also found that 61.7% of eligible subjects (92/149) had detectable Zika virus RNA in at least 1 urine specimen. The median time to the loss of RNA detection in urine was 8 days (95% CI, 6 to 10), and the 95th percentile of time was 39 days (95% CI, 31 to 47).

Fifteen subjects (10.1%) had detectable Zika virus RNA in urine but not serum, and 55 (36.7%) had RNA in serum but not urine.

Fifty-six percent of eligible male subjects (31/55) had Zika virus RNA in at least 1 semen specimen. The median time to loss of RNA detection in semen was 34 days (95% CI, 28 to 41), and the 95th percentile of time was 81 days (95% CI, 64 to 98).

The researchers noted that 11 of the 55 subjects had Zika virus RNA in their semen at their last visit and were still being followed at the time the NEJM article was written. The maximum duration of RNA detection was 125 days after the onset of symptoms.

Zika virus RNA levels were detectable in few saliva samples, with 10.2% of eligible subjects (15/147) having detectable levels in at least 1 saliva specimen.

Only 1 of 50 women (2%) had detectable Zika virus RNA in vaginal secretions.

“The findings of this study are important for both diagnostic and prevention purposes,” said study author Eli Rosenberg, PhD, of Emory University in Atlanta, Georgia.

“The results fully support current CDC sexual transmission recommendations but also provide critical information to help in understanding how often and how long evidence of Zika virus can be found in different body fluids. This knowledge is key to improving accuracy and effectiveness of testing methods while providing important baseline information for future research.”

Photo by Juan D. Alfonso

A study published in NEJM provides evidence that Zika virus RNA remain longer in blood and semen than in other body fluids, which suggests these may be superior diagnostic specimens.

This is the first study in which researchers examined multiple body fluids for the presence of Zika virus over a length of time.

The team sought to determine the frequency and duration of detectable Zika virus RNA in serum, saliva, urine, semen, and vaginal secretions.

They collected such specimens from 150 men and women in Puerto Rico who initially tested positive for Zika virus in urine or blood. The specimens were collected weekly for the first month and then at 2 months, 4 months, and 6 months.

The researchers tested all specimens using the Trioplex RT-PCR assay, a test that can be used to detect dengue, chikungunya, and Zika virus RNA. There have been allegations that this assay is less effective than a test used to detect Zika virus alone.

The researchers also performed validation analyses for the use of the Trioplex RT-PCR assay in semen. And they tested serum using the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

The US Centers for Disease Control and Prevention (CDC) developed both Zika MAC-ELISA and the Trioplex RT-PCR assay. This research was supported by the CDC.

After sample testing was complete, the researchers used parametric Weibull regression models to estimate the time to the loss of Zika virus RNA, which they reported in medians and 95th percentiles.

Results

The researchers said 88% of subjects (132/150) had detectable Zika virus RNA in at least 1 serum specimen. The median time to the loss of RNA detection in serum was 14 days (95% confidence interval [CI], 11 to 17), and the 95th percentile of time was 54 days (95% CI, 43 to 64).

The team also found that 61.7% of eligible subjects (92/149) had detectable Zika virus RNA in at least 1 urine specimen. The median time to the loss of RNA detection in urine was 8 days (95% CI, 6 to 10), and the 95th percentile of time was 39 days (95% CI, 31 to 47).

Fifteen subjects (10.1%) had detectable Zika virus RNA in urine but not serum, and 55 (36.7%) had RNA in serum but not urine.

Fifty-six percent of eligible male subjects (31/55) had Zika virus RNA in at least 1 semen specimen. The median time to loss of RNA detection in semen was 34 days (95% CI, 28 to 41), and the 95th percentile of time was 81 days (95% CI, 64 to 98).

The researchers noted that 11 of the 55 subjects had Zika virus RNA in their semen at their last visit and were still being followed at the time the NEJM article was written. The maximum duration of RNA detection was 125 days after the onset of symptoms.

Zika virus RNA levels were detectable in few saliva samples, with 10.2% of eligible subjects (15/147) having detectable levels in at least 1 saliva specimen.

Only 1 of 50 women (2%) had detectable Zika virus RNA in vaginal secretions.

“The findings of this study are important for both diagnostic and prevention purposes,” said study author Eli Rosenberg, PhD, of Emory University in Atlanta, Georgia.

“The results fully support current CDC sexual transmission recommendations but also provide critical information to help in understanding how often and how long evidence of Zika virus can be found in different body fluids. This knowledge is key to improving accuracy and effectiveness of testing methods while providing important baseline information for future research.”

Photo by Juan D. Alfonso

A study published in NEJM provides evidence that Zika virus RNA remain longer in blood and semen than in other body fluids, which suggests these may be superior diagnostic specimens.

This is the first study in which researchers examined multiple body fluids for the presence of Zika virus over a length of time.

The team sought to determine the frequency and duration of detectable Zika virus RNA in serum, saliva, urine, semen, and vaginal secretions.

They collected such specimens from 150 men and women in Puerto Rico who initially tested positive for Zika virus in urine or blood. The specimens were collected weekly for the first month and then at 2 months, 4 months, and 6 months.

The researchers tested all specimens using the Trioplex RT-PCR assay, a test that can be used to detect dengue, chikungunya, and Zika virus RNA. There have been allegations that this assay is less effective than a test used to detect Zika virus alone.

The researchers also performed validation analyses for the use of the Trioplex RT-PCR assay in semen. And they tested serum using the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

The US Centers for Disease Control and Prevention (CDC) developed both Zika MAC-ELISA and the Trioplex RT-PCR assay. This research was supported by the CDC.

After sample testing was complete, the researchers used parametric Weibull regression models to estimate the time to the loss of Zika virus RNA, which they reported in medians and 95th percentiles.

Results

The researchers said 88% of subjects (132/150) had detectable Zika virus RNA in at least 1 serum specimen. The median time to the loss of RNA detection in serum was 14 days (95% confidence interval [CI], 11 to 17), and the 95th percentile of time was 54 days (95% CI, 43 to 64).

The team also found that 61.7% of eligible subjects (92/149) had detectable Zika virus RNA in at least 1 urine specimen. The median time to the loss of RNA detection in urine was 8 days (95% CI, 6 to 10), and the 95th percentile of time was 39 days (95% CI, 31 to 47).

Fifteen subjects (10.1%) had detectable Zika virus RNA in urine but not serum, and 55 (36.7%) had RNA in serum but not urine.

Fifty-six percent of eligible male subjects (31/55) had Zika virus RNA in at least 1 semen specimen. The median time to loss of RNA detection in semen was 34 days (95% CI, 28 to 41), and the 95th percentile of time was 81 days (95% CI, 64 to 98).

The researchers noted that 11 of the 55 subjects had Zika virus RNA in their semen at their last visit and were still being followed at the time the NEJM article was written. The maximum duration of RNA detection was 125 days after the onset of symptoms.

Zika virus RNA levels were detectable in few saliva samples, with 10.2% of eligible subjects (15/147) having detectable levels in at least 1 saliva specimen.

Only 1 of 50 women (2%) had detectable Zika virus RNA in vaginal secretions.

“The findings of this study are important for both diagnostic and prevention purposes,” said study author Eli Rosenberg, PhD, of Emory University in Atlanta, Georgia.

“The results fully support current CDC sexual transmission recommendations but also provide critical information to help in understanding how often and how long evidence of Zika virus can be found in different body fluids. This knowledge is key to improving accuracy and effectiveness of testing methods while providing important baseline information for future research.”

SEATTLE – HIV-positive women treated with cryotherapy for cervical intraepithelial neoplasia (CIN) 2/3 were 52% more likely than women treated with loop excision to have a recurrence within 2 years, according to a randomized trial in Kenya.

The investigators called on the World Health Organization and other groups to support loop excision as the first-line option for HIV-positive women in sub-Saharan Africa and other low-resource settings, but the findings also support its use, when possible, in Western countries.

[email protected]

SEATTLE – HIV-positive women treated with cryotherapy for cervical intraepithelial neoplasia (CIN) 2/3 were 52% more likely than women treated with loop excision to have a recurrence within 2 years, according to a randomized trial in Kenya.

The investigators called on the World Health Organization and other groups to support loop excision as the first-line option for HIV-positive women in sub-Saharan Africa and other low-resource settings, but the findings also support its use, when possible, in Western countries.

[email protected]

SEATTLE – HIV-positive women treated with cryotherapy for cervical intraepithelial neoplasia (CIN) 2/3 were 52% more likely than women treated with loop excision to have a recurrence within 2 years, according to a randomized trial in Kenya.

The investigators called on the World Health Organization and other groups to support loop excision as the first-line option for HIV-positive women in sub-Saharan Africa and other low-resource settings, but the findings also support its use, when possible, in Western countries.

[email protected]

Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

[email protected]

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

[email protected]

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

[email protected]