Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Background: Early hospice referral among Medicare patients is associated with lower rates of hospital admission, intensive care unit admission, and in-hospital death. However, it is not known whether there is association between early hospice referral and health care costs among patients with maintenance hemodialysis.

Among 154,186 (20%) patients receiving hospice service at the time of death, 41.5% enrolled in hospice within 3 days of death. Because more patients were referred to hospice very close to the time of death, the Medicare cost for hospice patients was similar to those patients not referred to hospice ($10,756 vs. $10,871; P = .08). Longer lengths of stay in hospice beyond 3 days were associated with lower rates of health care utilization and costs. Late hospice referral was also associated with inadequate pain control and emotional needs.

The study was not able to capture patients who had end-stage renal disease but were on hemodialysis. Patients with private insurance or those covered by Veterans Affairs were not included.

Bottom line: Half of hospice referrals among patients with maintenance hemodialysis occur within the last 3 day of life, which has no significant effect on end-of-life costs and health care utilization.

Citation: Wachterman MW et al. Association between hospice length of stay, health care utilization, and Medicare costs at the end of life among patients who received maintenance hemodialysis. Jama Intern Med. 2018;178(6):792-9.

Dr. Katsouli is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

An observational study showed that women without meditation training who spent more time in a mindful state had lower ratings on a scale of menopausal symptoms. Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.

“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.

Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.

Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.

Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.

Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.

To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.

The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.

The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).

The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.

In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).

Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).

Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).

The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.

These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.

Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”

“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”

Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”

Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.

[email protected]

SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.

An observational study showed that women without meditation training who spent more time in a mindful state had lower ratings on a scale of menopausal symptoms. Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.

“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.

Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.

Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.

Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.

Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.

To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.

The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.

The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).

The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.

In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).

Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).

Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).

The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.

These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.

Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”

“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”

Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”

Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.

[email protected]

SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.

An observational study showed that women without meditation training who spent more time in a mindful state had lower ratings on a scale of menopausal symptoms. Furthermore, mindfulness had the greatest positive effect on menopausal symptoms for those women with the highest self-reported stress levels.

“In this cross-sectional study, mindfulness was associated with lower menopausal symptom burden. In women with higher stress, the magnitude of association between mindfulness and menopausal symptoms appeared more robust,” said Richa Sood, MD, speaking at the annual meeting of the North American Menopause Society.

Menopausal symptoms can exist alongside many other midlife issues because women often are trying to keep many balls in the air: This age group may be facing aging parents, a household with teenagers, and work-related pressures, she noted.

Thus, menopausal symptoms can be amplified by stressors. New mood problems – or worsening of preexisting ones – can interfere with work productivity and negatively affect relationships. Life satisfaction can take a steep dive during midlife for some women, said Dr. Sood of the Mayo Clinic, Rochester, Minn.

Could mindfulness be effective for stress management in this complex landscape of physiological and lifespan changes? “Mindfulness is paying attention,” said Dr. Sood. Practitioners of mindfulness focus on purposeful attention, staying in the present moment, and avoiding judgment.

Mindfulness may work as a stress-management tool for a variety of reasons, said Dr. Sood. The technique can help retrain people with tendencies for emotional reactivity in stressful situations; additionally, the focus on the present and on observation, rather than judgment, may help avoid maladaptive rumination.

To see how mindfulness in everyday life could affect the burden of menopausal symptoms, Dr. Sood and her collaborators designed an observational, cross-sectional study of 1,744 women aged 40-64 years.

The investigators used three scales in their assessments. The first, the Menopause Rating Scale (MRS), is an 11-item scale ranging from 0 to 44 that assesses psychological, somatovegetative, and urogenital domains. The second, the Perceived Stress Scale 4 (PSS-4), is a four-item scale that is a global measure of stress over the last 4 weeks, with tallied scores in the 0-16 range. Finally, the Mindful Attention Awareness Scale (MAAS) is a 15-item scale that captures how frequently respondents are in a mindful state during their daily life, with higher scores meaning more mindfulness.

The 1,744 women were seen in a women’s health clinic over the period of one year. Participants were a mean 53.4 years old (standard deviation, 6.1 years). Almost all were white (93%), most were married (82.7%), and most also had at least a 4-year college degree (64.6%) and were employed (65.3%).

The investigators mapped each scale against each of the others, which yielded three plots. In the first, higher MAAS scores were correlated with lower MRS scores (correlation, –0.49; P less than .001), which means that more time in a mindful state was associated with less severe menopausal symptoms.

In the second plot, lower MRS scores were associated with lower PSS-4 scores (correlation, 0.55; P less than .001). The last plot mapped PSS-4 scores against MAAS scores, showing that higher MAAS scores were correlated with lower PSS-4 scores, which means that more time in a mindful state was also associated with less perceived stress (correlation, –0.53; P less than .001).

Most of these associations remained statistically significant after multivariable linear regression analysis and breaking out the subscales of the MRS. Only the association between higher MAAS scores and the somatovegetative domain of the PSS-4 lost significance (P = 0.44).

Next, Dr. Sood and her collaborators probed how higher perceived stress, as measured by higher PSS-4 scores, altered the effects that mindful activity had on menopausal symptoms (as measured by the MRS).

The effect of mindfulness became stronger in the milieu of higher perceived stress. At a relatively low PSS-4 value of 4, the MRS score dropped 1.53 points for each one-point increase in the MAAS total score. However, with a PSS-4 score of 12, the decrease in MRS was 2.27 points for each one-point increase in MAAS, and with the maximum perceived stress score of 16, the MRS fell 2.64 points for each one-point increase in the MAAS score.

These findings are set against the backdrop of previous literature linking mindfulness to positive health behaviors and outcomes, she said, noting that work looking specifically at mindfulness-based stress reduction in peri- and postmenopausal women showed a halving of symptoms and improved quality of life.

Dr. Sood said that the present study was observational only, noting that it looked only at time spent in a mindful state in an untrained cohort of women in midlife. “Trait, or dispositional, mindfulness appears to be protective against stress and symptoms in midlife women,” she commented. “More mindful women may be choosing to shift their attention to more pleasant aspects of life, rather than their symptoms.”

“If you allow me to speculate a bit,” Dr. Sood continued, “the underpinnings of psychological symptoms rest in threat-focused attention and emotional reactivity – so the mindfulness approach appears to fit very well to impact such a change.”

Mindfulness, she added, “might be a tool to impact the emotional component of the overall experience, thereby decreasing the total suffering.” However, she noted that what’s needed are studies with a more heterogeneous population, as well as ones designed to tease out causality. Still, “the current study adds to the wealth of data supporting the role of mindfulness in various settings for impacting positive change in health and behaviors.”

Dr. Sood reported that she has ownership stake in the Global Center for Resiliency and Well-Being.

[email protected]

SOURCE: Sood R et al. NAMS 2018, Top-Scoring Abstract Session.

Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.

HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.

The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.

Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.

“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”

The authors did not report any disclosures.

[email protected]

SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.

Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.

HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.

The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.

Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.

“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”

The authors did not report any disclosures.

[email protected]

SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.

Myeloperoxidase (MPO) expression was significantly higher in hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) cases when compared with cirrhotic patients, according to a study of 59 patients with HCV-related liver disease.

HCV is the main cause of liver disease, wrote Mohamed Abdel-Hamed, MD, of Minia University in Egypt, and his colleagues. In addition, HCV is associated with significant oxidative stress, which has been identified as a significant metabolic pathway culminating in hepatic cirrhosis, liver failure, and liver cancer. Thus the researchers studied the role of MPO, an oxidative enzyme released at sites of inflammation, in the possible etiology of HCV-related liver cancer.

The patients were divided into two groups, 25 with HCC and 34 with chronic liver diseases with cirrhosis. All patients were examined immunohistochemically to demonstrate the expression of myeloperoxidase, according to the report published in Meta Gene.

Subjects with HCC showed markedly increased MPO expression when compared with MPO expression in hepatocytes of subjects with liver cirrhosis, who mostly showed a mild degree of expression. In addition, no mild expression of MPO was detected in the subjects with HCC. These findings were highly statistically significant (P less than .0001), according to Dr. Abdel-Hamed and his colleagues.

“The present study showed that marked expression of MPO plays an important role in the pathogenesis of HCV-associated HCC,” the authors stated. “This study could provide valuable, predictive parameters that can be used clinically in the prognosis of HCC patients.”

The authors did not report any disclosures.

[email protected]

SOURCE: Abdel-Hamid M et al. Meta Gene. 2018 Dec;18:1-8.

DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.

It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.

“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.

Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.

Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.

• CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.

Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).

Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.

Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.

Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.

But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.

The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.

Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.

But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.

“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.

Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.

Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.

Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.

“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.

DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.

It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.

“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.

Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.

Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.

• CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.

Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).

Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.

Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.

Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.

But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.

The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.

Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.

But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.

“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.

Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.

Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.

Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.

“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.

DALLAS – With the approaching midterm elections and Congress’ relative silence on health care policy this year, new health care legislation is unlikely in the immediate foreseeable future. But that does not mean the door to federal changes in health care policy is completely closed, according to Robert S. Saunders, PhD, of the Duke–Margolis Center for Health Policy, Durham, N.C.

It’s simply more likely to come from the new leadership at the Department of Health & Human Services including Secretary Alex Azar, Center for Medicare & Medicaid Services Administrator Seema Verma, and Center for Medicare & Medicaid Innovation Director Adam Boehler. In his keynote address for the American Gastroenterological Association’s Partners in Value meeting, Dr. Saunders gave attendees an overview of the current landscape in Washington and what they might expect in the coming months.

“Assuming congressional gridlock continues, HHS is a primary outlet for policy,” Dr. Saunders said, also noting CMMI’s pledge to make value-based payment a priority.

Broadly speaking, six goals comprise the current administration’s future vision within CMS, Dr. Saunders said. CMS has been encouraging payment reform innovation and benefit flexibility in Medicare Advantage and promoting private sector leadership with payment reform.

Three other goals include using CMMI to increase alternative payment model availability to specialists, expanding patients’ access to their own health data, and adding more outcomes measures but reducing the total number of measures.

• CMS is also collecting information on how it might reform the Stark Law to streamline value-based payment (VBP) arrangements or establish a mechanism for direct provider contracting.

Dr. Saunders highlighted two health policy developments already announced. First, CMS will continue to offer bundled payment options through the Bundled Payments for Care Improvement Advanced initiative, Dr. Saunders said. That program presents opportunities related to treatment of GI hemorrhage, GI obstruction, and most liver disorders (excepting cancer, cirrhosis, and alcoholic hepatitis).

Then, CMS is proposing several changes to existing programs, though it remains to be seen how those will develop. One of those is the proposed modification of the Accountable Care Organization program to shorten the period ACOs can spend in upside risk, thereby pushing for more downside risk taking. Instead of having 6 years in upside risk getting 50% of savings, the proposed Pathways to Success would reduce that period to 2 years of upside risk, after which the ACOs would be responsible for shared losses in adddition to potentially receiving savings.

Another proposed change is to make payments sites neutral so that Medicare clinical visits are charged the same regardless of whether they occur at a doctor’s office or in a hospital outpatient setting. Currently, hospital outpatient visits are reimbursed at a higher amount than are those in private physicians offices.

Finally, a new proposed rule would collapse payments for evaluation and management services into two tiers, which would apply only to office and outpatient E/M codes.

But it’s not clear yet how hard CMS will push for implementation of these changes. For example, the proposed rule on E/M policy is the most significant push so far to reduce documentation from this administration, Dr. Saunders said, but medical groups, particularly specialists, oppose the rule because they argue it incentivizes short, repeat visits.

The three probable scenarios are that CMS moves forward with the new rule, that CMS scales back and retains the existing system, or that the “medical community pushes for an alternative to E/M with a framework that rewards doctors for their time,” Dr. Saunders said. The final rule, likely to come down by November, will also offer some insight into how forcefully CMS will promote its agenda, according to Dr. Saunders.

Hearing these points “helps confirm that we are all headed toward this value-based world, and so we should start to ready our practices in the way that we internally compensate physicians and the way we engage with patients toward that value-based world,” Michael Weinstein, MD, president of the Digestive Health Physicians Association, said in an interview following the keynote.

But Dr. Weinstein expressed skepticism about CMS’ power to alter regulations sufficiently to really move forward into value-based care more broadly. He pointed out the various obstacles in the private sector that simply require legislative fixes, such as Stark Law modernization; increased transparency on price, outcomes, and quality measures; and interoperability between systems; among others.

“You have to keep knocking CMS to make the changes, but if CMS makes changes, it only makes changes for Medicare,” Dr. Weinstein said. Many states have laws requiring commercial carriers to follow the same federal rules that are set up for Medicare, but those are not universal and remain limited in scope.

Dr. Saunders also discussed the Physician-Focused Payment Model Technical Advisory Committee (PTAC), created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to review new options for alternative payment models.

Since beginning to accept submissions in December 2016, PTAC has reviewed two GI models in 2017: Project Sonar and a comprehensive colonoscopy APM. Project Sonar focuses on creation of an IBD/Crohn’s medical home. Despite reservations about proprietary technology and about the evidence on Project Sonar, PTAC has recommended the program for further testing. The comprehensive colonoscopy APM, however, was withdrawn after preliminary reviews because the PTAC was concerned the proposal “was too reliant on site-of-service shift and wanted more information on how it would lead to better integrated care,” Dr. Saunders explained.

Though PTAC’s existence led to hope early on that it might stimulate the creation of APMs and help them spread, the reality has been much shakier.

“CMS has not implemented any of the models PTAC has approved for use, and CMS has also not yet created a formal pathway for limited testing,” Dr. Saunders said. That has left members uncertain about the future.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.

copyright itsmejust/Thinkstock

The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.

In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.

Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).

In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).

The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.

The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.

However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.

The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
 

SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.

Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.

copyright itsmejust/Thinkstock

The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.

In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.

Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).

In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).

The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.

The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.

However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.

The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
 

SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.

Immunization of pregnant women with the Tdap vaccine during weeks 27-30 of pregnancy yielded the higher concentration of protective pertussis toxin antibodies in neonates, compared with neonates not exposed to the vaccine, based on data from more than 600 pregnancies.

copyright itsmejust/Thinkstock

The Centers for Disease Control and Prevention recommends Tdap vaccination for pregnant women between 27 and 35 weeks’ gestation, but “data on pertussis antibody concentrations following maternal Tdap immunization are limited because of small cohort size or differing immunization schedules,” wrote C. Mary Healy, MD, of Baylor College of Medicine, Houston and her colleagues.

In an observational study published in JAMA, the researchers reviewed data from 626 pregnancies and births at a single tertiary care center in Texas. The average age of the mothers was 30 years; 41% were white, 27% Hispanic, 26% black, 5% Asian, and 1% another ethnicity. Of these, 312 received the Tdap vaccine at an average gestation of 31 weeks, while 314 women were not immunized.

Overall, the geometric mean concentration (GMC) of neonatal umbilical cord pertussis toxin antibodies among infants exposed to Tdap was 47.3 IU/mL, compared with 12.9 IU/mL for unexposed infants, yielding a GMC ratio of 3.6 (P less than .001).

In addition, pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher were significantly more common in Tdap-exposed vs. Tdap-unexposed neonates (86% vs. 37%, 72% vs. 17%, 59% vs. 12%, respectively).

The GMC of pertussis toxin antibodies was highest when the vaccine was given during weeks 27-30, after which the GMC declined, the researchers noted.

The study was limited by several factors including the observational design, which does not support causes and effect analysis, the use of data from a single center, and the lack of pre- and postimmunization serum samples for comparison, and the absence of data on women immunized during the second trimester, the researchers wrote.

However, the results support data from previous studies, and were strengthened by the large study population. The findings suggest that “following U.S. immunization recommendations and in accordance with current understanding of the kinetics of placental transfer, optimal time to administer Tdap vaccine to maximize pertussis toxin antibodies at birth may be early in the third trimester, with the window of 27 through 30 weeks of gestation yielding the highest cord blood levels,” the researchers said.

The study was supported in part by the Centers for Disease Control and Prevention. Dr. Healy disclosed relationships with Sanofi Pasteur, Novartis Vaccines, Pfizer, and Novavax.
 

SOURCE: Healy C et al. JAMA. 2018 Oct 9;320(14):1464-70.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

TORONTO – Brigatinib proved superior to crizotinib for achieving progression-free survival in patients with inhibitor-naive anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer in the first interim results from the multicenter, open-label, phase 3 ALTA-1L trial.

Sharon Worcester/MDedge News

In fact, the primary endpoint of the study – blinded independent review committee–assessed progression-free survival (PFS) – was met at this first analysis. The next-generation ALK inhibitor brigatinib reduced the chance of progression or death by 51% as compared with crizotinib – the current first-line standard of care in this population, D. Ross Camidge, MD, reported at the World Conference on Lung Cancer.

“At a median follow-up of 9-11 months, 26% [of 137 patients] on the brigatinib arm and 46% [of 138 patients] on the crizotinib arm had experienced a PFS event. Median PFS was not reached for the brigatinib arm and was 9.8 months for the crizotinib arm; the hazard ratio for progression or death was 0.49 and highly statistically significant,” said Dr. Camidge, director of thoracic oncology and the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center, Aurora, at the meeting sponsored by the International Association for the Study of Lung Cancer.

The findings were published simultaneously in the New England Journal of Medicine.

The 12-month PFS rate estimate was 67% for brigatinib and 43% for crizotinib, and the investigator-assessed hazard ratio for PFS was 0.45. Overall survival data are immature, Dr. Camidge added, noting that the PFS hazard ratios for those with versus those without prior chemotherapy were 0.35 and 0.55, respectively.

“PFS consistently favored brigatinib across all other subgroups,” he said. “Although the confidence intervals overlap, the effect size appears greater among those with baseline [CNS] disease than among those without [HR, 0.2 vs. 0.72].”

Data suggest that CNS progression among those with CNS disease at baseline tends to be an earlier event than either extra-CNS progression in general or CNS progression in those without baseline CNS disease. “Consequently, this first interim analysis may be preferentially emphasizing drug efficacy differences within the subgroup in whom the earlier progression events are occurring,” Dr. Camidge said.

As for overall objective responses, the rates were numerically higher with brigatinib versus crizotinib (70% vs. 60%), but were not statistically different in the two groups. “However, the median duration of confirmed responses was not reached for brigatinib and [was] 11.1 months with crizotinib, with the 12-month [probability] of sustained response being 75% for brigatinib and 41% for crizotinib,” he added.

Further, among those with measurable CNS lesions, brigatinib demonstrated a significantly higher intracranial response rate of 78% versus 29% (odds ratio, 10.42), and when those with nonmeasurable CNS disease were included in the intracranial response assessment, the odds ratio was 13.

Median intracranial PFS among those with CNS involvement at baseline was not reached in the brigatinib arm versus 5.6 months with crizotinib, for a highly statistically significant hazard ratio of 0.27. “Which, given that the median PFS for crizotinib in the overall population ... was 9.8 months, again emphasizes how CNS events in this subgroup tend to occur early,” he noted.

Study subjects had stage IIIB/IV ALK-positive non–small cell lung cancer (NSCLC) based on local ALK testing, Eastern Cooperative Oncology Group performance status of 0-2, no more than one prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor therapy, Dr. Camidge said, noting that asymptomatic, untreated brain metastases were allowed and crossover to the brigatinib arm was permitted for those with blinded independent review committee–assessed progression on crizotinib.

Those randomized to the brigatinib arm had a median age of 58 years and received 180 mg daily with a 7-day lead-in at 90 mg. Those randomized to the crizotinib group had a median age of 60 years and received 250 mg twice daily. Prior chemotherapy for advanced disease was received by 26% and 27% and brain metastasis was present in 29% and 30% of patients in the arms, respectively.

The most common treatment-emergent adverse events of grade 3 or higher in the brigatinib patients were laboratory abnormalities such as creatinine phosphokinase, lipase, and amylase increases, and the most common in the crizotinib group were gastrointestinal effects, transaminitis, bradycardia, peripheral edema, and vision disturbances.

Discontinuations caused by adverse events occurred in 12% and 9% of the brigatinib and crizotinib patients, respectively, he said. No clinical cases of pancreatitis occurred in either arm, there was no difference in the incidence of any grade myalgia or musculoskeletal pain between arms, and there was no grade 3 or greater myalgia or musculoskeletal pain reported.

Early-onset interstitial lung disease, however, “appears to be a unique side effect of brigatinib,” Dr. Camidge noted.

Although interstitial lung disease/pneumonitis occurred in both groups, onset at days 3-8 after treatment initiation occurred only with brigatinib, he said, adding that “it only occurred in 3% of cases – half the rate seen in the postcrizotinib setting.”

The PROFILE 1014 study established crizotinib as the standard first-line therapy for advanced ALK-rearranged NSCLC, showing superior PFS versus pemetrexed doublet chemotherapy (HR, 0.45), but median PFS with crizotinib in that trial was only 10.9 months, Dr. Camidge said.

The next-generation ALK inhibitor brigatinib, however, has demonstrated broad preclinical activity against ALK resistance mutations, has excellent CNS penetration, and is the only ALK inhibitor with marked activity against multiple epidermal growth factor receptor–mutant cell lines, he said. “It has already shown significant activity both within the CNS and extracranially in the postcrizotinib setting, where it has consistently demonstrated the longest reported median PFS [up to 16.7 months] of any licensed or experimental ALK inhibitor.”

The ALTA-1L study provides a head-to-head comparison of brigatinib and crizotinib in a real-world setting, and the findings demonstrate that “brigatinib represents a promising new treatment for inhibitor-naive, ALK-rearranged NSCLC,” he said.

In a press statement, Dr. Camidge further stated that, based on these findings, brigatinib is set to become a first-line treatment option for ALK-positive lung cancer, adding that, “even with only 9-11 months of follow-up, the efficacy of brigatinib is clearly superior to crizotinib. A lot of the initial difference is driven by an effect on brain metastases, which tend to be an earlier progression event. However, once differences in control of disease outside the brain have time to manifest, it is possible the PFS improvement may increase.”

Both Dr. Camidge and invited discussant Fiona Blackhall, PhD, noted that the tolerability of brigatinib may be “even better in the real world,” as most of the 29% of patients on the brigatinib arm with adverse event–related dose reductions had “paper toxicities” for which the clinical impact is not well understood.

The rate of dose reductions for adverse events with brigatinib was higher in ALTA-1L than that seen in earlier studies of the second-generation ALK inhibitor alectinib, said Dr. Blackhall, professor and chair in thoracic oncology at the University of Manchester (England).

“We need to be sure that these dose reductions are appropriate and not potentially compromising efficacy,” she added.

Dr. Blackhall also suggested that sequential use of crizotinib and other ALK inhibitors like brigatinib should be evaluated and that the potential impact of ALK inhibitor selection “on the spectrum and type of resistance mutations and mechanisms” should be considered.

“Brigatinib is a new first-line treatment option for patients with ALK-positive non–small cell lung cancer. ... But in the absence of direct comparison of next-generation ALK inhibitors, it is going to take some time before we can determine whether there is indeed – if there ever will be – a ‘best’ ALK inhibitor for our patients,” she said.

Dr. Camidge has received honoraria from Arrys/Kyn, AstraZeneca, Biothera, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Genoptix, Hansoh, Ignyta, Lycera, Mersana Therapeutics, Novartis, Orion, Revolution Medicines, Roche/Genentech, and Takeda, and has received research funding from ARIADTakeda. Dr. Blackhall reported research funding from Amgen, AstraZeneca, Novartis, and Pfizer, and has served has an advisory board member, consultant, or speaker for AbbVie, Boehringer Ingelheim, Cell Medica, Medivation, Merck, Regeneron, Roche, and Takeda.

[email protected]

SOURCE: Camidge DR et al. WCLC 2018, Abstract PL02.03.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

A 40-year-old man presents with severe right flank pain for 1 hour. He has had this in the past when he passed a kidney stone. Urinalysis shows greater than 100 red blood cells per high power field (HPF). CT shows a 6-mm stone in the left ureter.

What do you recommend for therapy?

A. IV ketorolac and IV fluids.

B. IV morphine and IV fluids.

C. IV morphine.

D. IV ketorolac.

This is a common scenario, especially in emergency department settings and acute care clinics. Patients arrive in severe pain because of renal colic from kidney stones. Standard teaching that I received many years ago was that this patient should receive IV fluid to “help float the stone out” and narcotic pain medications to treat the severe pain the patient was in.

Is there good evidence that this is the best therapy?

There are scant data on the practice of IV fluid for treatment of renal stone passage. W. Patrick Springhart, MD, and his colleagues studied 43 patients who presented to the ED for treatment of renal colic.¹ All patients had CT evaluation for stones and received intravenous analgesia. Twenty patients were randomized to receive 2 L of normal saline over 2 hours, and 23 patients received minimal IV saline (20 mL/hour). There were no differences between the two groups in pain scores, narcotic requirements, or stone passage rates.

In an older study, Tom-Harald Edna, PhD, and colleagues studied 60 patients with ureteral colic, randomizing them to receive either no fluid or 3 L of IV fluid over 6 hours.² There was no significant difference in pain between treatment groups.

A Cochrane analysis in 2012 concluded that there was no reliable evidence to support the use of high-volume fluid therapy in the treatment of acute ureteral colic.³

Standard treatment of pain for renal colic has been to use narcotics. In a randomized, double-blind trial comparing ketorolac and meperidine, William Cordell, MD, and his colleagues found that pain relief was superior in ketorolac-treated patients. Seventy-five percent of ketorolac patients had a 50% reduction in pain scores versus only 23% of the patients who received meperidine (P less than .001).⁴

Anna Holdgate and Tamara Pollock reviewed 20 studies that evaluated NSAIDs and narcotics for acute renal colic. They concluded that patients treated with NSAIDs had greater pain relief with less vomiting than did patients treated with narcotics.⁵

In the past decade, tamsulosin has been frequently used in patients with renal stones to possibly help with pain and promote more rapid stone passage. A recent randomized, controlled trial with 512 patients, authored by Andrew Meltzer, MD, and his colleagues, showed no improvement in stone passage rate in patients taking tamsulosin, compared with the rate seen with placebo.⁶

Previously published meta-analyses of multiple studies have shown a benefit to the use of alpha-blockers. Thijs Campschroer and colleagues included 67 studies that altogether included 10,509 participants.⁷ They found that the use of alpha-blockers led to possibly shorter stone expulsion times (3.4 days), less NSAID use, and fewer hospitalizations, with the evidence graded as low to moderate quality. Stone size seems to matter because use of alpha-blockers does not seem to make a difference for stones larger than 5 mm.

I think IV ketorolac would be the best of the options presented here for this patient. If a patient can safely take NSAIDs, those are probably the best option. There does not appear to be any reason to bolus hydrate patients with acute renal colic.

Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. J Endourol. 2006 Oct;20(10):713-6.

2. Scand J Urol Nephrol. 1983;17(2):175-8.

3. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004926.

4. Ann Emerg Med. 1996 Aug;28(2):151-8.

5. BMJ. 2004 Jun 12;328(7453):1401.

6. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.

7. Cochrane Database Syst Rev. 2018 Apr 5;4:CD008509.

People with systemic sclerosis who are anti-RNPC3 antibody positive were significantly more likely to have moderate to severe gastrointestinal dysfunction in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.

GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.

Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.

In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.

Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.

Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.

Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).

Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.

“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.

This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).

Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).

Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).

However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).

Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.

They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).

“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.

“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.

The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.

SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763

People with systemic sclerosis who are anti-RNPC3 antibody positive were significantly more likely to have moderate to severe gastrointestinal dysfunction in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.

GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.

Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.

In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.

Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.

Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.

Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).

Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.

“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.

This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).

Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).

Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).

However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).

Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.

They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).

“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.

“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.

The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.

SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763

People with systemic sclerosis who are anti-RNPC3 antibody positive were significantly more likely to have moderate to severe gastrointestinal dysfunction in a two-center study, suggesting that anti-RNPC3 antibody status could serve as a biomarker for risk stratification of GI dysmotility in this patient population.

GI dysfunction is the most common internal complication of systemic sclerosis (SSc), affecting up to 90% of patients, and it presents with “striking” heterogeneity, first author Zsuzsanna H. McMahan, MD, of John Hopkins University, Baltimore, and her colleagues wrote in Arthritis Care & Research.

Recent published reports have suggested a link between anti-RNPC3 antibodies (for example, anti-U11/U12 ribonucleoprotein) and GI dysmotility, but have had limited generalizability and did not assess for any associations with distinct GI outcomes, the study authors noted.

In the current study, the investigators compared 37 SSc patients with severe GI dysfunction who required total parenteral nutrition and 38 SSc patients without symptoms of GI dysfunction (modified Medsger severity score of 0) in the Johns Hopkins Scleroderma Center database.

Patients were included in this “discovery cohort” if they had both clinical data and banked serum, and met 2013 ACR/EULAR criteria, 1980 ACR criteria, or at least three of five features of CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. The presence of severe GI dysmotility was determined by physician documentation in the clinical notes and/or the presence of esophageal dysmotility, gastroparesis, or small bowel dysmotility.

Anti-RNPC3 antibodies were more prevalent among patients on total parenteral nutrition (14% vs. 3%; P = .11), a finding that the authors said was consistent with the published literature.

Patients in the severe GI group also were significantly more likely to be male (38% vs. 16%; P = .031), to be black (43% vs. 13%; P less than or equal to .01), to have diffuse disease (65% vs. 34%; P less than or equal to .01), to have myopathy (24% vs. 5%; P = .05), and to have anti-U3RNP antibodies (12% vs. 0%; P = .05).

Severe GI patients were also significantly less likely to have anti-RNA pol 3 antibodies (3% vs. 25%; P = .01). Two patients in the severe GI group were double-positive for antibodies, having both anti-RNPC3 antibodies and antibodies to either Ro52 or PM-Scl.

“Since the number of anti-RNPC3 antibody positive patients in the John Hopkins discovery study was small, but anti-RNPC3 antibodies were over four times more frequent than expected in the severe GI group, we pursued additional analyses to understand this association using the current Pittsburgh Scleroderma cohort,” the research team explained.

This cohort included 39 anti-RNPC3 antibody positive cases and 117 matched anti-RNPC3 negative controls. Moderate to severe GI dysfunction (Medsger GI score of 2 or higher) was present in 36% of anti-RNPC3 positive patients vs. 15% of anti-RNPC3 negative patients (P less than or equal to. 01).

Anti-RNPC3-positive patients were more likely to be male (31% vs. 15%; P = .04), to be black (18% vs. 6%; P = .02), to have esophageal dysmotility (93% vs. 62%; P less than .01), and to have interstitial lung disease (ILD, 77% vs. 35%; P less than .01).

Even after adjustment for relevant covariates and potential confounders, moderate to severe GI disease was associated with anti-RNPC3 antibodies. For example, in an unadjusted model, moderate to severe GI disease was associated with a nearly fourfold higher likelihood of having anti-RNPC3 antibodies (odds ratio = 3.8; 95% confidence interval, 1.5-9.8). And in a model adjusted for age and race, moderate to severe GI disease was again associated with a 3.8 times increased odds of having anti-RNPC3 antibodies (95% CI, 1.4-10.0). But there was no significant association for age (OR = 1.0; 95% CI, 0.95-1.0) or black race (OR = 2.4; 95% CI, 0.7-8.5).

However, in a model adjusted for age, race, ILD, diffuse cutaneous disease, and myopathy, patients with moderate to severe GI disease continued to have a 3.8-fold increased odds of having anti-RNPC3 antibodies (95% CI, 1.0-14.3).

Older age at first visit, black race, diffuse cutaneous disease, and myopathy did not seem to play a role in the risk of having anti-RNPC3 antibodies.

They also observed an association with ILD, which they said trended toward significance (OR = 2.8; 95% CI, 1.0-8.2).

“The association between anti-RNPC3 antibodies and both pulmonary fibrosis and esophageal dysmotility in SSc is interesting. High rates of ILD are reported in association with anti-RNPC3 antibodies in SSc, with anti-RNPC3 antibody positive patients having an estimated 70% prevalence of ILD,” the study authors noted.

“In addition, recent studies suggest that microaspiration in SSc patients with uncontrolled reflux could contribute to the development of pulmonary fibrosis. Anti-RNPC3 antibodies may identify a specific subset of patients at higher risk for microaspiration that would benefit from more aggressive GERD management,” they wrote.

The Scleroderma Research Foundation funded the study. Additional support was provided by the Jerome L. Greene Scholar Award, the Rheumatology Research Foundation, the Johns Hopkins Clinician Scientist Career Development Award, and National Institutes of Health grants. No relevant conflicts of interest were declared by the authors.

SOURCE: McMahan Z et al. Arthritis Care Res. 2018 Sep 22. doi: 10.1002/acr.23763

SAN ANTONIO – Unplanned readmissions declined among tracheostomy/ventilator-dependent children whose discharge process involved a pulmonary nurse practitioner to coordinate continuity of care, a study of more than 70 patients has found.

Tara Haelle/MDedge News

Despite an increase over time in the rate of discharges, readmissions fell, Sarah Barry, CRNP, of Children’s Hospital of Philadelphia (CHOP), said at the annual meeting of the American College of Chest Physicians.

“The technology-dependent pediatric population who is going home with tracheostomy and ventilator dependence is at risk for hospital readmission, and having an advanced practice provider in a continuity role promotes adherence to our standards of practice and improves transition to home,” Ms. Barry said in an interview.

She noted previous research showing that 40% of 109 home mechanical ventilation patients discharged between 2003 and 2009 had unplanned readmissions, 28% of which occurred within the first month after discharge.

Nearly two thirds (64%) of those readmissions were related to a pulmonary and/or tracheostomy problem. That study also found that changes in condition management 1 week before discharge, such as medications, ventilator settings, or feeding regimens, was associated with unplanned readmission.

That research “makes us ask ourselves if our readmissions are avoidable and what can we do to get these kids home safe and to keep them home,” Ms. Barry told attendees, adding that CHOP was unhappy with their readmission rates.

“Kids were often not making it to their first pulmonary appointment, and it was a burden for these families,” she said. “We questioned whether or not having a nurse practitioner in a role to promote adherence to our standards would have a positive impact on our unplanned route.”

They evaluated the effect of such an NP on unplanned readmissions among tracheostomy/ventilator-supported children. The NP’s role was to track patients, mostly from the progressive care unit, who required a tracheostomy and ventilator and were expected to be discharged home or to a long-term care facility. The NP provided continuity for medical management and coordinated care at discharge.

“We also do not make changes for 2 weeks before discharge so that we can focus on all the other coordination that goes into getting these kids home,” Ms. Barry said.

She reviewed the patients’ electronic charts to record time to scheduled follow-up visit, days until hospital readmission, admitting diagnosis at readmission, and length of stay after readmission. With consideration for the time needed for transition into this new process, the population studied was assessed within three cohorts.

The first cohort comprised the 22 children discharged between April 2016 and March 2017, the full year before a pulmonary NP began coordinating the discharge process. These patients averaged 1.8 discharges per month with an initial follow-up of 2-12 weeks.

Just over a quarter (27%) of the first cohort were readmitted before their scheduled follow-up, ranging from 2 to 25 days after discharge. Five percent were readmitted within a week of discharge, and 27% were readmitted within a month; their average length of stay was 13 days after readmission. Most (83%) of these discharges were respiratory related while the other 17% were gastrointestinal related.

The second cohort involved the 11 patients discharged between April 2017 and August 2017, the first 5 months after a pulmonary NP began overseeing the discharge readiness process.

“We chose 5 months because it took about 5months for me to develop my own protocols and standards of practice,” Ms. Barry explained.

An average 2.2 discharges occurred monthly with 2-8 weeks of initial postdischarge follow-up. Though nearly half these children (45%) were readmitted before their scheduled follow-up, their length of stay was shorter, an average of 11 days.

Readmission within a week after discharge occurred among 27% of the children, and 45% of them were readmitted within a month of discharge. Sixty percent of these patients were readmitted for respiratory issues, compared with 40% with GI issues.

The third cohort included all 38 patients discharged from September 2017 to August 2018, the year after a pulmonary NP had become fully established in the continuity role, with an average 3.2 discharges occurred per month. Readmission rates were considerably lower: Eighteen percent of patients were readmitted before their scheduled follow-up appointment, which ranged from 1 to 13 weeks after discharge.

Five percent were readmitted within a week of discharge, and 24% were readmitted within a month, ranging from 1 to 26 days post discharge. But length of stay was shorter still at an average of 9 days.

The reasons for readmission varied more in this cohort: While 56% were respiratory related, 22% were related to fever, and 11% were related to neurodevelopment concerns or social reasons, such as necessary involvement of social services.

Ms. Barry’s colleague, Howard B. Panitch, MD, also on the staff of CHOP, noted during the discussion that the NP’s role is invaluable in “keeping the inpatient teams honest.

“She reminds her colleagues in critical care that you can’t make that ventilator change when on your way out the door or very close to discharge.”

Ms. Barry had no disclosures. No external funding was noted.

SOURCE: Barry S et al. CHEST 2018 Oct. doi: 10.1016/j.chest.2018.08.743.

SAN ANTONIO – Unplanned readmissions declined among tracheostomy/ventilator-dependent children whose discharge process involved a pulmonary nurse practitioner to coordinate continuity of care, a study of more than 70 patients has found.

Tara Haelle/MDedge News

Despite an increase over time in the rate of discharges, readmissions fell, Sarah Barry, CRNP, of Children’s Hospital of Philadelphia (CHOP), said at the annual meeting of the American College of Chest Physicians.

“The technology-dependent pediatric population who is going home with tracheostomy and ventilator dependence is at risk for hospital readmission, and having an advanced practice provider in a continuity role promotes adherence to our standards of practice and improves transition to home,” Ms. Barry said in an interview.

She noted previous research showing that 40% of 109 home mechanical ventilation patients discharged between 2003 and 2009 had unplanned readmissions, 28% of which occurred within the first month after discharge.

Nearly two thirds (64%) of those readmissions were related to a pulmonary and/or tracheostomy problem. That study also found that changes in condition management 1 week before discharge, such as medications, ventilator settings, or feeding regimens, was associated with unplanned readmission.

That research “makes us ask ourselves if our readmissions are avoidable and what can we do to get these kids home safe and to keep them home,” Ms. Barry told attendees, adding that CHOP was unhappy with their readmission rates.

“Kids were often not making it to their first pulmonary appointment, and it was a burden for these families,” she said. “We questioned whether or not having a nurse practitioner in a role to promote adherence to our standards would have a positive impact on our unplanned route.”

They evaluated the effect of such an NP on unplanned readmissions among tracheostomy/ventilator-supported children. The NP’s role was to track patients, mostly from the progressive care unit, who required a tracheostomy and ventilator and were expected to be discharged home or to a long-term care facility. The NP provided continuity for medical management and coordinated care at discharge.

“We also do not make changes for 2 weeks before discharge so that we can focus on all the other coordination that goes into getting these kids home,” Ms. Barry said.

She reviewed the patients’ electronic charts to record time to scheduled follow-up visit, days until hospital readmission, admitting diagnosis at readmission, and length of stay after readmission. With consideration for the time needed for transition into this new process, the population studied was assessed within three cohorts.

The first cohort comprised the 22 children discharged between April 2016 and March 2017, the full year before a pulmonary NP began coordinating the discharge process. These patients averaged 1.8 discharges per month with an initial follow-up of 2-12 weeks.

Just over a quarter (27%) of the first cohort were readmitted before their scheduled follow-up, ranging from 2 to 25 days after discharge. Five percent were readmitted within a week of discharge, and 27% were readmitted within a month; their average length of stay was 13 days after readmission. Most (83%) of these discharges were respiratory related while the other 17% were gastrointestinal related.

The second cohort involved the 11 patients discharged between April 2017 and August 2017, the first 5 months after a pulmonary NP began overseeing the discharge readiness process.

“We chose 5 months because it took about 5months for me to develop my own protocols and standards of practice,” Ms. Barry explained.

An average 2.2 discharges occurred monthly with 2-8 weeks of initial postdischarge follow-up. Though nearly half these children (45%) were readmitted before their scheduled follow-up, their length of stay was shorter, an average of 11 days.

Readmission within a week after discharge occurred among 27% of the children, and 45% of them were readmitted within a month of discharge. Sixty percent of these patients were readmitted for respiratory issues, compared with 40% with GI issues.

The third cohort included all 38 patients discharged from September 2017 to August 2018, the year after a pulmonary NP had become fully established in the continuity role, with an average 3.2 discharges occurred per month. Readmission rates were considerably lower: Eighteen percent of patients were readmitted before their scheduled follow-up appointment, which ranged from 1 to 13 weeks after discharge.

Five percent were readmitted within a week of discharge, and 24% were readmitted within a month, ranging from 1 to 26 days post discharge. But length of stay was shorter still at an average of 9 days.

The reasons for readmission varied more in this cohort: While 56% were respiratory related, 22% were related to fever, and 11% were related to neurodevelopment concerns or social reasons, such as necessary involvement of social services.

Ms. Barry’s colleague, Howard B. Panitch, MD, also on the staff of CHOP, noted during the discussion that the NP’s role is invaluable in “keeping the inpatient teams honest.

“She reminds her colleagues in critical care that you can’t make that ventilator change when on your way out the door or very close to discharge.”

Ms. Barry had no disclosures. No external funding was noted.

SOURCE: Barry S et al. CHEST 2018 Oct. doi: 10.1016/j.chest.2018.08.743.

SAN ANTONIO – Unplanned readmissions declined among tracheostomy/ventilator-dependent children whose discharge process involved a pulmonary nurse practitioner to coordinate continuity of care, a study of more than 70 patients has found.

Tara Haelle/MDedge News

Despite an increase over time in the rate of discharges, readmissions fell, Sarah Barry, CRNP, of Children’s Hospital of Philadelphia (CHOP), said at the annual meeting of the American College of Chest Physicians.

“The technology-dependent pediatric population who is going home with tracheostomy and ventilator dependence is at risk for hospital readmission, and having an advanced practice provider in a continuity role promotes adherence to our standards of practice and improves transition to home,” Ms. Barry said in an interview.

She noted previous research showing that 40% of 109 home mechanical ventilation patients discharged between 2003 and 2009 had unplanned readmissions, 28% of which occurred within the first month after discharge.

Nearly two thirds (64%) of those readmissions were related to a pulmonary and/or tracheostomy problem. That study also found that changes in condition management 1 week before discharge, such as medications, ventilator settings, or feeding regimens, was associated with unplanned readmission.

That research “makes us ask ourselves if our readmissions are avoidable and what can we do to get these kids home safe and to keep them home,” Ms. Barry told attendees, adding that CHOP was unhappy with their readmission rates.

“Kids were often not making it to their first pulmonary appointment, and it was a burden for these families,” she said. “We questioned whether or not having a nurse practitioner in a role to promote adherence to our standards would have a positive impact on our unplanned route.”

They evaluated the effect of such an NP on unplanned readmissions among tracheostomy/ventilator-supported children. The NP’s role was to track patients, mostly from the progressive care unit, who required a tracheostomy and ventilator and were expected to be discharged home or to a long-term care facility. The NP provided continuity for medical management and coordinated care at discharge.

“We also do not make changes for 2 weeks before discharge so that we can focus on all the other coordination that goes into getting these kids home,” Ms. Barry said.

She reviewed the patients’ electronic charts to record time to scheduled follow-up visit, days until hospital readmission, admitting diagnosis at readmission, and length of stay after readmission. With consideration for the time needed for transition into this new process, the population studied was assessed within three cohorts.

The first cohort comprised the 22 children discharged between April 2016 and March 2017, the full year before a pulmonary NP began coordinating the discharge process. These patients averaged 1.8 discharges per month with an initial follow-up of 2-12 weeks.

Just over a quarter (27%) of the first cohort were readmitted before their scheduled follow-up, ranging from 2 to 25 days after discharge. Five percent were readmitted within a week of discharge, and 27% were readmitted within a month; their average length of stay was 13 days after readmission. Most (83%) of these discharges were respiratory related while the other 17% were gastrointestinal related.

The second cohort involved the 11 patients discharged between April 2017 and August 2017, the first 5 months after a pulmonary NP began overseeing the discharge readiness process.

“We chose 5 months because it took about 5months for me to develop my own protocols and standards of practice,” Ms. Barry explained.

An average 2.2 discharges occurred monthly with 2-8 weeks of initial postdischarge follow-up. Though nearly half these children (45%) were readmitted before their scheduled follow-up, their length of stay was shorter, an average of 11 days.

Readmission within a week after discharge occurred among 27% of the children, and 45% of them were readmitted within a month of discharge. Sixty percent of these patients were readmitted for respiratory issues, compared with 40% with GI issues.

The third cohort included all 38 patients discharged from September 2017 to August 2018, the year after a pulmonary NP had become fully established in the continuity role, with an average 3.2 discharges occurred per month. Readmission rates were considerably lower: Eighteen percent of patients were readmitted before their scheduled follow-up appointment, which ranged from 1 to 13 weeks after discharge.

Five percent were readmitted within a week of discharge, and 24% were readmitted within a month, ranging from 1 to 26 days post discharge. But length of stay was shorter still at an average of 9 days.

The reasons for readmission varied more in this cohort: While 56% were respiratory related, 22% were related to fever, and 11% were related to neurodevelopment concerns or social reasons, such as necessary involvement of social services.

Ms. Barry’s colleague, Howard B. Panitch, MD, also on the staff of CHOP, noted during the discussion that the NP’s role is invaluable in “keeping the inpatient teams honest.

“She reminds her colleagues in critical care that you can’t make that ventilator change when on your way out the door or very close to discharge.”

Ms. Barry had no disclosures. No external funding was noted.

SOURCE: Barry S et al. CHEST 2018 Oct. doi: 10.1016/j.chest.2018.08.743.