A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.

The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.

The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.

“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.

The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.

The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.

In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).

The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.

In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.

Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.

“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.

The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.

SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.

A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.

The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.

The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.

“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.

The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.

The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.

In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).

The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.

In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.

Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.

“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.

The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.

SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.

A system that automatically evaluates bone scans produces a measure that is prognostic for overall survival (OS) in patients with metastatic prostate cancer, investigators are reporting.

The automated bone scan index (BSI) produced by the artificial intelligence–based system provides prognostic discrimination beyond other established risk markers, investigators reported in JAMA Oncology.

The automated BSI also provides significantly greater discriminative ability compared with the current standard, which is manual assessment by counting metastatic lesion numbers, according to Andrew J. Armstrong, MD, of Duke University, Durham, N.C. and his coauthors.

“Incorporating the aBSI into clinical practice to supplement nuclear medicine reports may permit a more objective analysis of bone scan changes over time and their clinical relevance to patient care,” Dr. Armstrong and colleagues said.

The BSI represents tumor burden as a percentage of total skeletal weight. The system used in this study automates BSI methods by using artificial neural networks to detect metastatic hot spots and classify them as malignant or benign.

The automated system was evaluated in a preplanned secondary analysis of a randomized clinical trial of imiquimod in men with chemotherapy-naive metastatic castration-resistant prostate cancer. Evaluable bone scans were available for 721 out of 1,245 total enrollees from 241 sites in 37 countries.

In the secondary analysis, investigators found that baseline aBSI was significantly associated with OS. Risk of death increased by 20% for every doubling of the aBSI score (hazard ratio, 1.20; 95% confidence interval, 1.14-1.26; P less than .001).

The association remained significant in a multivariable model adjusting for five variables associated with OS: albumin, lactate dehydrogenase, C-reactive protein, serum prostate-specific antigen, and Eastern European geographic region.

In addition, the automated BSI had a better discriminating ability in prognosticating OS as compared to manual lesion counting (C-index of 0.63 and 0.60, respectively; P = .03), investigators said.

Secondary analyses showed the automated BSI was also associated with time to symptomatic progression, prostate cancer specific survival, and time to opiate use for cancer pain.

“These data support the clinical utility of the automated BSI, given its association with clinically relevant outcomes that are critically important in patient care,” wrote Dr. Armstrong and his colleagues.

The study was funded by EXINI Diagnostics AB, a subsidiary of Progenics Pharmaceuticals. The researchers reported disclosures related to EXINI Diagnostics AB and Active Biotech.

SOURCE: Armstrong AJ et al. JAMA Oncol. 2018 May 17. doi: 10.1001/jamaoncol.2018.1093.

Providing free and open access to its high-quality peer-reviewed articles has always been important to Federal Practitioner, but finding them hasn’t always been easy for our readers and researchers. That has now changed. The full text of all Federal Practitioner peer-reviewed articles, editorials, and columns published after December 2014 are now available through the National Library of Medicine (NLM) PubMed Central (PMC) index (https://www.ncbi.nlm.nih.gov/pmc/).

To be sure, Federal Practitioner has always made it easy for print and digital subscribers to find our articles. Print journal subscriptions have been—and will remain—free to the 35,000 subscribers. Furthermore, anyone can access articles online (http://mdedge.com/fedprac), in the Federal Practitioner app, or in our digital edition (http://www.fedprac-digital.com/).

However, until now access beyond our base of loyal readers has been limited. Inclusion in PMC provides a much broader audience for Federal Practitioner authors, because PMC is an integral part of the NLM MEDLINE/PubMed database of 28 million biomedical citations and abstracts from more than 5,000 journals. All PMC articles appear in PubMed searches. On a typical day, about 2.5 million users in the US access PubMed to perform about 3 million searches and access 9 million page views.¹

Inclusion also means that Federal Practitioner has passed a rigorous scientific and technical review of its content. Being included in PMC is a recognition of the quality of scholarship the journal publishes and a pledge of our continuing commitment to the highest quality of clinical education and research. Young investigators, clinician-educators, midcareer professionals, and others seeking to launch or enhance an academic career may want to consider or reconsider Federal Practitioner as the destination for manuscript submission.

One of the goals of this journal has been to provide a forum for federal health care providers (HCPs) to discuss and share with other federal colleagues. Federal HCPs from the Military Health System (MHS), Veterans Health Administration (VHA), and Indian Health Service (IHS) have addressed questions in Federal Practitioner that might not be explored elsewhere. Yet something important was missing from those conversations—engagement with the larger public health community. PubMed and PMC enable an ongoing conversation among health care researchers and providers. These are the places where researchers go to understand and respond to the questions that shape their research and clinical care. Now, Federal Practitioner authors can contribute more fully in ongoing debates.

As large integrated health care systems, the VHA, MHS, and IHS confront and address key public health care policy issues. Whether it’s the responsible and safe prescribing of opioids, the resource allocation decisions regarding the treatment of hepatitis C, or addressing suicide risk, the experience of federal HCPs must be a part of the public health debate. Moreover, many Federal Practitioner articles focus not just on preliminary research, but on the practical aspects of implementing patient-centered care. All US HCPs may benefit from hearing about federal providers challenges and success in providing patient-centered care.

Making available the complete text of all the articles furthers the Federal Practitioner mission: to educate federal HCPs and provide a forum for sharing health-care related studies, best practices, guidelines, program profiles, and case studies. We are excited to provide even more benefits for publication in Federal Practitioner. This journal welcomes submissions from new authors, well-traveled scholars, and everyone in between. Come on, join the conversation.

Providing free and open access to its high-quality peer-reviewed articles has always been important to Federal Practitioner, but finding them hasn’t always been easy for our readers and researchers. That has now changed. The full text of all Federal Practitioner peer-reviewed articles, editorials, and columns published after December 2014 are now available through the National Library of Medicine (NLM) PubMed Central (PMC) index (https://www.ncbi.nlm.nih.gov/pmc/).

To be sure, Federal Practitioner has always made it easy for print and digital subscribers to find our articles. Print journal subscriptions have been—and will remain—free to the 35,000 subscribers. Furthermore, anyone can access articles online (http://mdedge.com/fedprac), in the Federal Practitioner app, or in our digital edition (http://www.fedprac-digital.com/).

However, until now access beyond our base of loyal readers has been limited. Inclusion in PMC provides a much broader audience for Federal Practitioner authors, because PMC is an integral part of the NLM MEDLINE/PubMed database of 28 million biomedical citations and abstracts from more than 5,000 journals. All PMC articles appear in PubMed searches. On a typical day, about 2.5 million users in the US access PubMed to perform about 3 million searches and access 9 million page views.¹

Inclusion also means that Federal Practitioner has passed a rigorous scientific and technical review of its content. Being included in PMC is a recognition of the quality of scholarship the journal publishes and a pledge of our continuing commitment to the highest quality of clinical education and research. Young investigators, clinician-educators, midcareer professionals, and others seeking to launch or enhance an academic career may want to consider or reconsider Federal Practitioner as the destination for manuscript submission.

One of the goals of this journal has been to provide a forum for federal health care providers (HCPs) to discuss and share with other federal colleagues. Federal HCPs from the Military Health System (MHS), Veterans Health Administration (VHA), and Indian Health Service (IHS) have addressed questions in Federal Practitioner that might not be explored elsewhere. Yet something important was missing from those conversations—engagement with the larger public health community. PubMed and PMC enable an ongoing conversation among health care researchers and providers. These are the places where researchers go to understand and respond to the questions that shape their research and clinical care. Now, Federal Practitioner authors can contribute more fully in ongoing debates.

As large integrated health care systems, the VHA, MHS, and IHS confront and address key public health care policy issues. Whether it’s the responsible and safe prescribing of opioids, the resource allocation decisions regarding the treatment of hepatitis C, or addressing suicide risk, the experience of federal HCPs must be a part of the public health debate. Moreover, many Federal Practitioner articles focus not just on preliminary research, but on the practical aspects of implementing patient-centered care. All US HCPs may benefit from hearing about federal providers challenges and success in providing patient-centered care.

Making available the complete text of all the articles furthers the Federal Practitioner mission: to educate federal HCPs and provide a forum for sharing health-care related studies, best practices, guidelines, program profiles, and case studies. We are excited to provide even more benefits for publication in Federal Practitioner. This journal welcomes submissions from new authors, well-traveled scholars, and everyone in between. Come on, join the conversation.

Providing free and open access to its high-quality peer-reviewed articles has always been important to Federal Practitioner, but finding them hasn’t always been easy for our readers and researchers. That has now changed. The full text of all Federal Practitioner peer-reviewed articles, editorials, and columns published after December 2014 are now available through the National Library of Medicine (NLM) PubMed Central (PMC) index (https://www.ncbi.nlm.nih.gov/pmc/).

To be sure, Federal Practitioner has always made it easy for print and digital subscribers to find our articles. Print journal subscriptions have been—and will remain—free to the 35,000 subscribers. Furthermore, anyone can access articles online (http://mdedge.com/fedprac), in the Federal Practitioner app, or in our digital edition (http://www.fedprac-digital.com/).

However, until now access beyond our base of loyal readers has been limited. Inclusion in PMC provides a much broader audience for Federal Practitioner authors, because PMC is an integral part of the NLM MEDLINE/PubMed database of 28 million biomedical citations and abstracts from more than 5,000 journals. All PMC articles appear in PubMed searches. On a typical day, about 2.5 million users in the US access PubMed to perform about 3 million searches and access 9 million page views.¹

Inclusion also means that Federal Practitioner has passed a rigorous scientific and technical review of its content. Being included in PMC is a recognition of the quality of scholarship the journal publishes and a pledge of our continuing commitment to the highest quality of clinical education and research. Young investigators, clinician-educators, midcareer professionals, and others seeking to launch or enhance an academic career may want to consider or reconsider Federal Practitioner as the destination for manuscript submission.

One of the goals of this journal has been to provide a forum for federal health care providers (HCPs) to discuss and share with other federal colleagues. Federal HCPs from the Military Health System (MHS), Veterans Health Administration (VHA), and Indian Health Service (IHS) have addressed questions in Federal Practitioner that might not be explored elsewhere. Yet something important was missing from those conversations—engagement with the larger public health community. PubMed and PMC enable an ongoing conversation among health care researchers and providers. These are the places where researchers go to understand and respond to the questions that shape their research and clinical care. Now, Federal Practitioner authors can contribute more fully in ongoing debates.

As large integrated health care systems, the VHA, MHS, and IHS confront and address key public health care policy issues. Whether it’s the responsible and safe prescribing of opioids, the resource allocation decisions regarding the treatment of hepatitis C, or addressing suicide risk, the experience of federal HCPs must be a part of the public health debate. Moreover, many Federal Practitioner articles focus not just on preliminary research, but on the practical aspects of implementing patient-centered care. All US HCPs may benefit from hearing about federal providers challenges and success in providing patient-centered care.

Making available the complete text of all the articles furthers the Federal Practitioner mission: to educate federal HCPs and provide a forum for sharing health-care related studies, best practices, guidelines, program profiles, and case studies. We are excited to provide even more benefits for publication in Federal Practitioner. This journal welcomes submissions from new authors, well-traveled scholars, and everyone in between. Come on, join the conversation.

When interpreting tacrolimus levels, it is important to monitor changes in red blood cells (RBC). A patient who had hepatitis C virus (HCV) genotype 3A lesson reinforced that lesson for clinicians in the dialysis unit at Fraser Health in Abbotsford, Canada who authored a recent case report. Ribavirin-induced anemia reduced the level of tacrolimus in the patien, the authors reported.

The patient, a 37-year-old man, developed renal failure and received a kidney transplant, which subsequently failed (due to complications likely related to HCV). He had been started on tacrolimus while waiting to go back on the transplant list. Eight years later, the patient restarted hemodialysis (HD), with a regimen of sofosbuvir and ribavirin (SOF/RBV). His whole-blood tacrolimus level was 6.6 ng/mL (target 4–6); his hemoglobin (Hb) level was 10.3 g/dL. Two months later, the patient left for a 1-month vacation. When he returned, his Hb was “dramatically low,” at 3.7 g/dL.

The clinicians put the ribavirin on hold and increased darbepoetin. The patient was given packed RBCs; a bone marrow biopsy ruled out myeloproliferative disorder. Two weeks later, the tacrolimus level was 1.0 mg/mL and then dropped to an undetectable level 5 days later. The clinicians increased the dose. During the next month, the patient’s Hb “gradually bounced back,” to > 10 g/dL, whereupon the clinicians restarted RBV. When the tacrolimus level reached 7.2 ng/mL, the dosages were gradually cut back.  Sofosbuvir and RBV were stopped a couple of months later. The patient’s HCV RNA level was undetectable 12 weeks after therapy finished.

Practitioners are always facing the dilemma of risk (anemia) vs benefit (efficacy) in deciding whether and how much RBV should be reduced in renal impairment, the case report authors say. They note that the guidelines for treatment-naïve genotype 3 patients have changed. The recommendation for SOF/RBV has been replaced by one for glecaprevir/pibrentasvir or SOF/velpatasvir.

With the availability of newer direct antivirals, they add, the case again supports the abandoning of RBV-containing regimens. In the “very unlikely instance” that RBV is warranted in a patient on HD, the clinicians advise careful monitoring of Hb, especially 1 month after RBV therapy has started. Consider increasing the dosage of erythropoietin-stimulating agents if the patient’s Hb is at the lower end of the target range.

The decision to increase tacrolimus dosage based on a lower tacrolimus whole-blood concentration induced by anemia is “debatable,” the clinicians say. Nevertheless, this case reminds practitioners to take account of changes in RBC counts when interpreting tacrolimus levels—especially when a drastic change is not expected.

Source:

Liu HY, Cheung CYS, Cooper SE. BMJ Case Rep. 2018;2018. pii: bcr-2017-222477.
doi: 10.1136/bcr-2017-222477.

When interpreting tacrolimus levels, it is important to monitor changes in red blood cells (RBC). A patient who had hepatitis C virus (HCV) genotype 3A lesson reinforced that lesson for clinicians in the dialysis unit at Fraser Health in Abbotsford, Canada who authored a recent case report. Ribavirin-induced anemia reduced the level of tacrolimus in the patien, the authors reported.

The patient, a 37-year-old man, developed renal failure and received a kidney transplant, which subsequently failed (due to complications likely related to HCV). He had been started on tacrolimus while waiting to go back on the transplant list. Eight years later, the patient restarted hemodialysis (HD), with a regimen of sofosbuvir and ribavirin (SOF/RBV). His whole-blood tacrolimus level was 6.6 ng/mL (target 4–6); his hemoglobin (Hb) level was 10.3 g/dL. Two months later, the patient left for a 1-month vacation. When he returned, his Hb was “dramatically low,” at 3.7 g/dL.

The clinicians put the ribavirin on hold and increased darbepoetin. The patient was given packed RBCs; a bone marrow biopsy ruled out myeloproliferative disorder. Two weeks later, the tacrolimus level was 1.0 mg/mL and then dropped to an undetectable level 5 days later. The clinicians increased the dose. During the next month, the patient’s Hb “gradually bounced back,” to > 10 g/dL, whereupon the clinicians restarted RBV. When the tacrolimus level reached 7.2 ng/mL, the dosages were gradually cut back.  Sofosbuvir and RBV were stopped a couple of months later. The patient’s HCV RNA level was undetectable 12 weeks after therapy finished.

Practitioners are always facing the dilemma of risk (anemia) vs benefit (efficacy) in deciding whether and how much RBV should be reduced in renal impairment, the case report authors say. They note that the guidelines for treatment-naïve genotype 3 patients have changed. The recommendation for SOF/RBV has been replaced by one for glecaprevir/pibrentasvir or SOF/velpatasvir.

With the availability of newer direct antivirals, they add, the case again supports the abandoning of RBV-containing regimens. In the “very unlikely instance” that RBV is warranted in a patient on HD, the clinicians advise careful monitoring of Hb, especially 1 month after RBV therapy has started. Consider increasing the dosage of erythropoietin-stimulating agents if the patient’s Hb is at the lower end of the target range.

The decision to increase tacrolimus dosage based on a lower tacrolimus whole-blood concentration induced by anemia is “debatable,” the clinicians say. Nevertheless, this case reminds practitioners to take account of changes in RBC counts when interpreting tacrolimus levels—especially when a drastic change is not expected.

Source:

Liu HY, Cheung CYS, Cooper SE. BMJ Case Rep. 2018;2018. pii: bcr-2017-222477.
doi: 10.1136/bcr-2017-222477.

When interpreting tacrolimus levels, it is important to monitor changes in red blood cells (RBC). A patient who had hepatitis C virus (HCV) genotype 3A lesson reinforced that lesson for clinicians in the dialysis unit at Fraser Health in Abbotsford, Canada who authored a recent case report. Ribavirin-induced anemia reduced the level of tacrolimus in the patien, the authors reported.

The patient, a 37-year-old man, developed renal failure and received a kidney transplant, which subsequently failed (due to complications likely related to HCV). He had been started on tacrolimus while waiting to go back on the transplant list. Eight years later, the patient restarted hemodialysis (HD), with a regimen of sofosbuvir and ribavirin (SOF/RBV). His whole-blood tacrolimus level was 6.6 ng/mL (target 4–6); his hemoglobin (Hb) level was 10.3 g/dL. Two months later, the patient left for a 1-month vacation. When he returned, his Hb was “dramatically low,” at 3.7 g/dL.

The clinicians put the ribavirin on hold and increased darbepoetin. The patient was given packed RBCs; a bone marrow biopsy ruled out myeloproliferative disorder. Two weeks later, the tacrolimus level was 1.0 mg/mL and then dropped to an undetectable level 5 days later. The clinicians increased the dose. During the next month, the patient’s Hb “gradually bounced back,” to > 10 g/dL, whereupon the clinicians restarted RBV. When the tacrolimus level reached 7.2 ng/mL, the dosages were gradually cut back.  Sofosbuvir and RBV were stopped a couple of months later. The patient’s HCV RNA level was undetectable 12 weeks after therapy finished.

Practitioners are always facing the dilemma of risk (anemia) vs benefit (efficacy) in deciding whether and how much RBV should be reduced in renal impairment, the case report authors say. They note that the guidelines for treatment-naïve genotype 3 patients have changed. The recommendation for SOF/RBV has been replaced by one for glecaprevir/pibrentasvir or SOF/velpatasvir.

With the availability of newer direct antivirals, they add, the case again supports the abandoning of RBV-containing regimens. In the “very unlikely instance” that RBV is warranted in a patient on HD, the clinicians advise careful monitoring of Hb, especially 1 month after RBV therapy has started. Consider increasing the dosage of erythropoietin-stimulating agents if the patient’s Hb is at the lower end of the target range.

The decision to increase tacrolimus dosage based on a lower tacrolimus whole-blood concentration induced by anemia is “debatable,” the clinicians say. Nevertheless, this case reminds practitioners to take account of changes in RBC counts when interpreting tacrolimus levels—especially when a drastic change is not expected.

Source:

Liu HY, Cheung CYS, Cooper SE. BMJ Case Rep. 2018;2018. pii: bcr-2017-222477.
doi: 10.1136/bcr-2017-222477.

Clinical question: What roles, training, and support do hospitalists have and perceive in the intensive care unit?

Background: There is a well-documented shortage of intensivists in the United States, which has left hospitalists to help fill the gap of care. Hospitalists, however, have varied levels of critical care knowledge and skills. In some regions, more than 80% of hospitalists deliver care in the ICU. It is unknown how much support hospitalized patients receive from board-certified critical care physicians.

Study design: Multistage cross-section survey.

Setting: Web-based survey initially sent through the Critical Care Task Force professional networks and later sent to 4,000 hospitalists randomly selected from Society of Hospital Medicine’s national electronic mailing list of 12,000 hospitalists.

Synopsis: This study includes 425 responses, approximately 10% of those solicited. Compared with the annual SHM survey, this included more hospitalists from academic hospitals (24% vs. 14.8%) and fewer from nonteaching hospitals (41% vs. 58.7%). A total of 77% of responders provide care in the ICU, with 66% serving as the attending physician.

Rural and nonacademic hospitalists are more prevalent in the ICU (96% rural vs. 73% nonrural; 90% nonacademic vs. 67% academic), are more likely to serve as the primary physician for all or most ICU patients (85% rural vs. 62% nonrural; 81% nonacademic vs. 44% academic), and provide all critical care services (55% rural vs. 10% nonrural; 64% nonacademic vs. 25% academic).

Many rural (43%) and nonacademic (42%) hospitalists feel that they are expected to practice beyond their perceived scope of expertise at least some of the time, which was correlated with perceived difficulty in transferring patients to higher levels of care. About 90% of rural hospitalists report at least insufficient support from board-certified intensivists. Of all responders in the study, 85% indicated interest in additional critical care training in some form, short of fellowship training.

Bottom line: Most hospitalists provide care in the ICU, however hospitalists provide critical care at significantly higher rates in rural and nonacademic hospital settings. This care is being provided with a perceived lack of intensivist support and training.

Citation: Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan 1;13(1):6-12.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Clinical question: What roles, training, and support do hospitalists have and perceive in the intensive care unit?

Background: There is a well-documented shortage of intensivists in the United States, which has left hospitalists to help fill the gap of care. Hospitalists, however, have varied levels of critical care knowledge and skills. In some regions, more than 80% of hospitalists deliver care in the ICU. It is unknown how much support hospitalized patients receive from board-certified critical care physicians.

Study design: Multistage cross-section survey.

Setting: Web-based survey initially sent through the Critical Care Task Force professional networks and later sent to 4,000 hospitalists randomly selected from Society of Hospital Medicine’s national electronic mailing list of 12,000 hospitalists.

Synopsis: This study includes 425 responses, approximately 10% of those solicited. Compared with the annual SHM survey, this included more hospitalists from academic hospitals (24% vs. 14.8%) and fewer from nonteaching hospitals (41% vs. 58.7%). A total of 77% of responders provide care in the ICU, with 66% serving as the attending physician.

Rural and nonacademic hospitalists are more prevalent in the ICU (96% rural vs. 73% nonrural; 90% nonacademic vs. 67% academic), are more likely to serve as the primary physician for all or most ICU patients (85% rural vs. 62% nonrural; 81% nonacademic vs. 44% academic), and provide all critical care services (55% rural vs. 10% nonrural; 64% nonacademic vs. 25% academic).

Many rural (43%) and nonacademic (42%) hospitalists feel that they are expected to practice beyond their perceived scope of expertise at least some of the time, which was correlated with perceived difficulty in transferring patients to higher levels of care. About 90% of rural hospitalists report at least insufficient support from board-certified intensivists. Of all responders in the study, 85% indicated interest in additional critical care training in some form, short of fellowship training.

Bottom line: Most hospitalists provide care in the ICU, however hospitalists provide critical care at significantly higher rates in rural and nonacademic hospital settings. This care is being provided with a perceived lack of intensivist support and training.

Citation: Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan 1;13(1):6-12.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Clinical question: What roles, training, and support do hospitalists have and perceive in the intensive care unit?

Background: There is a well-documented shortage of intensivists in the United States, which has left hospitalists to help fill the gap of care. Hospitalists, however, have varied levels of critical care knowledge and skills. In some regions, more than 80% of hospitalists deliver care in the ICU. It is unknown how much support hospitalized patients receive from board-certified critical care physicians.

Study design: Multistage cross-section survey.

Setting: Web-based survey initially sent through the Critical Care Task Force professional networks and later sent to 4,000 hospitalists randomly selected from Society of Hospital Medicine’s national electronic mailing list of 12,000 hospitalists.

Synopsis: This study includes 425 responses, approximately 10% of those solicited. Compared with the annual SHM survey, this included more hospitalists from academic hospitals (24% vs. 14.8%) and fewer from nonteaching hospitals (41% vs. 58.7%). A total of 77% of responders provide care in the ICU, with 66% serving as the attending physician.

Rural and nonacademic hospitalists are more prevalent in the ICU (96% rural vs. 73% nonrural; 90% nonacademic vs. 67% academic), are more likely to serve as the primary physician for all or most ICU patients (85% rural vs. 62% nonrural; 81% nonacademic vs. 44% academic), and provide all critical care services (55% rural vs. 10% nonrural; 64% nonacademic vs. 25% academic).

Many rural (43%) and nonacademic (42%) hospitalists feel that they are expected to practice beyond their perceived scope of expertise at least some of the time, which was correlated with perceived difficulty in transferring patients to higher levels of care. About 90% of rural hospitalists report at least insufficient support from board-certified intensivists. Of all responders in the study, 85% indicated interest in additional critical care training in some form, short of fellowship training.

Bottom line: Most hospitalists provide care in the ICU, however hospitalists provide critical care at significantly higher rates in rural and nonacademic hospital settings. This care is being provided with a perceived lack of intensivist support and training.

Citation: Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan 1;13(1):6-12.

Dr. Muñoa is a hospitalist at Denver Health Medical Center and an assistant professor of medicine at the University of Colorado at Denver, Aurora.

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”

Image by Lance Liotta

A signaling protein may be a “potent” therapeutic target for acute myeloid leukemia (AML), according to a paper published in the Journal of Experimental Medicine.

The protein, interleukin-1 receptor accessory protein (IL1RAP), is often highly expressed on the surface of leukemic stem cells (LSCs) but largely absent from normal hematopoietic stem cells.

Despite this, it wasn’t known whether LSCs require IL1RAP to survive and proliferate and whether inhibiting IL1RAP could be a successful way to treat AML.

Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York, and his colleagues conducted research to find out.

The team found that targeting IL1RAP via RNA interference, genetic deletion, or antibodies induced the death of AML cells, including LSCs, in vitro. These effects were seen in the absence of immune effector cells, indicating that AML cells intrinsically depend on IL1RAP.

In contrast, antibodies targeting IL1RAP had no effect on the growth and survival of normal hematopoietic cells.

In mice, IL1RAP antibody treatment inhibited the proliferation of AML cells without causing any negative side effects.

The researchers also found that IL1RAP’s role in AML is not restricted to the IL-1 receptor pathway.

The team found that IL1RAP enhances the activity of 2 other membrane receptor proteins, FLT3 and c-KIT, which are known to stimulate the proliferation of LSCs when activated by their ligands. IL1RAP antibodies inhibited the ability of these ligands to induce proliferation in AML cells.

“Our findings show that IL1RAP can amplify multiple key pathways in AML, demonstrating a much broader role for this protein in disease pathogenesis than previously appreciated,” Dr Steidl noted.

“Importantly, as IL1RAP is also overexpressed in the stem cells of chronic myeloid leukemia and high-risk myelodysplastic syndromes, there is significant therapeutic potential in further developing IL1RAP-directed targeting strategies.”

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

Photo courtesy of Janssen

The 140 mg capsules of Imbruvica® (ibrutinib) will remain on the market, according to Pharmacyclics LLC.

Pharmacyclics (an AbbVie company) and Janssen had planned to discontinue the capsules after introducing a single-tablet formulation of Imbruvica earlier this year.

However, the companies received negative feedback about the discontinuation and decided to keep the 140 mg capsules on the market.

In February, the US Food and Drug Administration (FDA) approved a single-tablet formulation of Imbruvica that is available in 4 doses—140 mg, 280 mg, 420 mg, and 560 mg.

Pharmacyclics and Janssen introduced this formulation to enable a once-a-day dosing regimen. The companies said the goal with the new formulation was to improve adherence because some patients had to take 3 or 4 pills every day to get the recommended dose of Imbruvica.

After introducing the new formulation, Pharmacyclics and Janssen planned to discontinue the 140 mg capsules.

Critics spoke out against this change in an article published in The Cancer Letter. They noted that discontinuing the old formulation would mean price increases for some patients. That’s because the single-tablet formulation of Imbruvica has the same price regardless of dose—$400 per tablet.

Patients on lower doses of Imbruvica would experience an increase in cost if they switched from the capsules to the tablet formulation. In fact, costs could triple for patients on the 140 mg dose.

Pharmacyclics argued that most patients on Imbruvica—those taking the 420 mg and 560 mg doses—would see no increase in out-of-pocket costs when transitioning to the single-tablet formulation.  And patients on the 560 mg dose would likely see a decrease in their out-of-pocket costs.

However, critics pointed to results of a recent pilot study, which indicated that the recommended dose of Imbruvica for patients with chronic lymphocytic leukemia (CLL)—420 mg—may be too high. The results suggested that CLL patients could receive lower doses of Imbruvica without a reduction in efficacy.

Therefore, keeping the 140 mg capsules on the market could mean lower costs for some CLL patients.

In addition to voicing concerns about costs, the critics pointed out that discontinuing the 140 mg capsules of Imbruvica would make it more difficult to adjust patients’ doses when needed.

Pharmacyclics said its YOU&i™ Dose Exchange Program can aid healthcare professionals in adjusting doses before patients have finished their current pack of Imbruvica. Patients would receive a “rapid shipment” of their new dose at no additional cost.

But the critics said this program “creates a barrier to optimal prescribing for some patients” and urged the FDA to review the safety of the program.

Roughly a month after the critics made this recommendation in The Cancer Letter article, Pharmacyclics announced that the 140 mg capsules of Imbruvica would remain on the market.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has released a list of companies that “may be pursuing gaming tactics to delay generic competition.”

FDA Commissioner Scott Gottlieb, MD, said the agency is taking steps to improve access to drugs and make them more affordable.

One of these steps is trying to prevent companies that market brand-name drugs from delaying the release of generic equivalents.

Dr Gottlieb explained that brand companies may create obstacles for generic developers to purchase samples of a brand-name drug.

“In general, generic drug developers need the samples of the brand drug to develop their generic product and/or to conduct testing to show that their product is bioequivalent to the brand drug for FDA approval,” he said.

“Without these samples, generic drug makers may not be able to develop generic alternatives. Yet the FDA has heard that some brand companies will adopt tactics to make it hard for the generic companies to purchase these brand drugs at a fair value and in the open marketplace.”

One such tactic is for brand companies to place restrictions in their commercial contracts or agreements with prescription drug distributors, wholesalers, or specialty pharmacies that limit their ability to sell samples to generic drug developers.

In other cases, brand companies may be preventing generic drug developers from accessing samples due to limited distribution programs required by a Risk Evaluation and Mitigation Strategy (REMS) with Elements to Assure Safe Use (ETASU).

“But I want to be very clear: a path to securing samples of brand drugs for the purpose of generic drug development should always be available,” Dr Gottlieb said. “Even in the case of limited distribution programs, such as those required by certain REMS, there should be a path forward for generic drug development.”

With this in mind, the FDA has released a list of brand companies that may have prevented generic drug developers from accessing samples. The list contains 52 brand-name drugs, including Pomalyst, Promacta, Revlimid, Tasigna, and Thalidomid.

Generic drug developers have reported trouble obtaining samples of these drugs and asked the FDA for assistance.

When the FDA receives such a request, the agency first determines whether the product in question has a REMS program with ETASU that may impact distribution.

If the FDA confirms the existence of such a program, the generic company can submit its bioequivalence testing protocol to the FDA. The agency then evaluates this protocol to ensure the plan for testing the product contains safety protections comparable to the brand product’s REMS program.

If a generic developer’s plans include appropriate protections, the developer can request that the FDA send a Safety Determination Letter to the brand company. This letter notes that the REMS program doesn’t prevent the brand company from selling its product to generic drug developers.

The FDA has issued 21 Safety Determination Letters to date, according to Dr Gottlieb.

If a generic drug developer has trouble obtaining samples of a drug for which there is no REMS program with ETASU, the FDA informs the developer that there are no FDA-required restrictions that would prevent it from obtaining samples.

The FDA also notifies the Federal Trade Commission (FTC) of requests from generic drug developers seeking assistance in obtaining samples from brand companies. And the FDA encourages generic drug developers to raise these cases with the FTC if they believe that anticompetitive conduct has taken place.

Children whose autism was not detected by the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months old were more likely to have delays in social, communication, and fine and gross motor skills at the time of the screen, compared with other children who had negative results, according to findings from a retrospective analysis of 68,197 screen-negative cases in the Norwegian Mother and Child Cohort Study.

Parents of children with false-negative M-CHAT results rated their children’s gross and fine motor skills and social and communication skills at 18 months as less developed than did parents of children with true-negative screens. For girls who had false-negative results and were later diagnosed with autism, the delays were more pronounced, compared with girls with true-negative results. Also, girls later diagnosed with autism were rated as less shy than girls with true-negative scores. Shyness was more common in boys later diagnosed with autism than in boys with true-negative scores.

“When trying to determine if a young child is exhibiting autism symptoms, clinicians should not rely solely on a single instrument but consider parental concerns and draw on other developmental surveillance instruments, as well as their clinical judgment. ... The clinicians also need to be particularly wary about discounting symptoms of social difficulties in girls because they may be masked by limited shyness or social inhibition,” wrote Roald A. Øien, MA, of the University of Tromsø (Norway) and Yale University in New Haven, Conn., and his associates in Pediatrics.

The researchers noted that the study was based on use of a previous M-CHAT version. The findings may not be relevant to the updated M-CHAT-R/F, which has 20 questions, new cutoffs, and a recommended follow-up interview.

Of the Norwegian children who were at least 40 months old at the time of the study, 67,969 had true-negative M-CHAT screens, and 228 had false-negative screens based on later diagnoses reported in the Autism Birth Cohort, a substudy of the Norwegian Mother and Child Cohort Study.

The 18-month-olds had been assessed with the M-CHAT, selected items from the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. Of the 23 pass-fail M-CHAT items, 6 are highly predictive of a later ASD diagnosis; a positive screen is failure of at least 2 of those 6 items.

Both boys and girls with false negatives were less social and had lower communication and gross motor skills, compared with their true-negative counterparts, but these differences were greater between false-negative and true-negative girls. Fine motor skills were also significantly lower in those with false negatives than in those with true negatives, but the magnitude was no different between girls and boys.

Overall, boys had more advanced gross motor skills and higher activity levels than girls, independent of true- or false-negative status.

In post hoc analyses, boys with false-negative results were rated as more shy than boys with true-negative results. Girls with false negatives were rated as less shy than girls with true negatives and boys with false negatives. Ratings of emotionality and activity did not differ among the children with true or false negatives.

The authors speculated that girls with false negatives may have “somewhat lower levels of social fearfulness or lower inhibitory control, compared with boys.”

The authors also suggested possible reasons for the false negatives, including parents’ difficulty in matching behaviors described in the M-CHAT with their children’s behaviors and the lack of graded responses on the M-CHAT, which may influence parents’ responses.

By comparison, the Ages and Stages Questionnaire “gives parents the opportunity to express that the children exhibit skills occasionally albeit inconsistently, which may allow them to express their concerns and perceptions in a more graded manner,” the authors wrote.

Another possible reason for false negatives, the authors suggested, is that symptoms in those with autism spectrum disorder may manifest differently in early childhood, partly depending on the level of the child’s verbal and nonverbal skills.

“We believe that our results contribute, at a fundamental level, to our understanding of early screening for ASD, and we highlight the discrepancy between hard cutoff criteria for autism and the social-communicative, developmental, and temperamental signatures of emerging or subthreshold autism phenotypes,” the authors wrote. They noted a need for screens that take into account temperament and verbal and nonverbal skill levels.

The research was funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway and Functional Genomics in Norway, the National Institute of Neurological Disorders and Stroke and the National Institute of Environmental Health Sciences. Dr Hornig coinvented an intestinal microbiome biomarker for autism which has patents assigned to Columbia University.

SOURCE: Øien RA et al. Pediatrics. 2018;141(6):e20173596.

Children whose autism was not detected by the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months old were more likely to have delays in social, communication, and fine and gross motor skills at the time of the screen, compared with other children who had negative results, according to findings from a retrospective analysis of 68,197 screen-negative cases in the Norwegian Mother and Child Cohort Study.

Parents of children with false-negative M-CHAT results rated their children’s gross and fine motor skills and social and communication skills at 18 months as less developed than did parents of children with true-negative screens. For girls who had false-negative results and were later diagnosed with autism, the delays were more pronounced, compared with girls with true-negative results. Also, girls later diagnosed with autism were rated as less shy than girls with true-negative scores. Shyness was more common in boys later diagnosed with autism than in boys with true-negative scores.

“When trying to determine if a young child is exhibiting autism symptoms, clinicians should not rely solely on a single instrument but consider parental concerns and draw on other developmental surveillance instruments, as well as their clinical judgment. ... The clinicians also need to be particularly wary about discounting symptoms of social difficulties in girls because they may be masked by limited shyness or social inhibition,” wrote Roald A. Øien, MA, of the University of Tromsø (Norway) and Yale University in New Haven, Conn., and his associates in Pediatrics.

The researchers noted that the study was based on use of a previous M-CHAT version. The findings may not be relevant to the updated M-CHAT-R/F, which has 20 questions, new cutoffs, and a recommended follow-up interview.

Of the Norwegian children who were at least 40 months old at the time of the study, 67,969 had true-negative M-CHAT screens, and 228 had false-negative screens based on later diagnoses reported in the Autism Birth Cohort, a substudy of the Norwegian Mother and Child Cohort Study.

The 18-month-olds had been assessed with the M-CHAT, selected items from the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. Of the 23 pass-fail M-CHAT items, 6 are highly predictive of a later ASD diagnosis; a positive screen is failure of at least 2 of those 6 items.

Both boys and girls with false negatives were less social and had lower communication and gross motor skills, compared with their true-negative counterparts, but these differences were greater between false-negative and true-negative girls. Fine motor skills were also significantly lower in those with false negatives than in those with true negatives, but the magnitude was no different between girls and boys.

Overall, boys had more advanced gross motor skills and higher activity levels than girls, independent of true- or false-negative status.

In post hoc analyses, boys with false-negative results were rated as more shy than boys with true-negative results. Girls with false negatives were rated as less shy than girls with true negatives and boys with false negatives. Ratings of emotionality and activity did not differ among the children with true or false negatives.

The authors speculated that girls with false negatives may have “somewhat lower levels of social fearfulness or lower inhibitory control, compared with boys.”

The authors also suggested possible reasons for the false negatives, including parents’ difficulty in matching behaviors described in the M-CHAT with their children’s behaviors and the lack of graded responses on the M-CHAT, which may influence parents’ responses.

By comparison, the Ages and Stages Questionnaire “gives parents the opportunity to express that the children exhibit skills occasionally albeit inconsistently, which may allow them to express their concerns and perceptions in a more graded manner,” the authors wrote.

Another possible reason for false negatives, the authors suggested, is that symptoms in those with autism spectrum disorder may manifest differently in early childhood, partly depending on the level of the child’s verbal and nonverbal skills.

“We believe that our results contribute, at a fundamental level, to our understanding of early screening for ASD, and we highlight the discrepancy between hard cutoff criteria for autism and the social-communicative, developmental, and temperamental signatures of emerging or subthreshold autism phenotypes,” the authors wrote. They noted a need for screens that take into account temperament and verbal and nonverbal skill levels.

The research was funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway and Functional Genomics in Norway, the National Institute of Neurological Disorders and Stroke and the National Institute of Environmental Health Sciences. Dr Hornig coinvented an intestinal microbiome biomarker for autism which has patents assigned to Columbia University.

SOURCE: Øien RA et al. Pediatrics. 2018;141(6):e20173596.

Children whose autism was not detected by the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months old were more likely to have delays in social, communication, and fine and gross motor skills at the time of the screen, compared with other children who had negative results, according to findings from a retrospective analysis of 68,197 screen-negative cases in the Norwegian Mother and Child Cohort Study.

Parents of children with false-negative M-CHAT results rated their children’s gross and fine motor skills and social and communication skills at 18 months as less developed than did parents of children with true-negative screens. For girls who had false-negative results and were later diagnosed with autism, the delays were more pronounced, compared with girls with true-negative results. Also, girls later diagnosed with autism were rated as less shy than girls with true-negative scores. Shyness was more common in boys later diagnosed with autism than in boys with true-negative scores.

“When trying to determine if a young child is exhibiting autism symptoms, clinicians should not rely solely on a single instrument but consider parental concerns and draw on other developmental surveillance instruments, as well as their clinical judgment. ... The clinicians also need to be particularly wary about discounting symptoms of social difficulties in girls because they may be masked by limited shyness or social inhibition,” wrote Roald A. Øien, MA, of the University of Tromsø (Norway) and Yale University in New Haven, Conn., and his associates in Pediatrics.

The researchers noted that the study was based on use of a previous M-CHAT version. The findings may not be relevant to the updated M-CHAT-R/F, which has 20 questions, new cutoffs, and a recommended follow-up interview.

Of the Norwegian children who were at least 40 months old at the time of the study, 67,969 had true-negative M-CHAT screens, and 228 had false-negative screens based on later diagnoses reported in the Autism Birth Cohort, a substudy of the Norwegian Mother and Child Cohort Study.

The 18-month-olds had been assessed with the M-CHAT, selected items from the Ages and Stages Questionnaire and the Emotionality Activity Sociability Temperament Survey. Of the 23 pass-fail M-CHAT items, 6 are highly predictive of a later ASD diagnosis; a positive screen is failure of at least 2 of those 6 items.

Both boys and girls with false negatives were less social and had lower communication and gross motor skills, compared with their true-negative counterparts, but these differences were greater between false-negative and true-negative girls. Fine motor skills were also significantly lower in those with false negatives than in those with true negatives, but the magnitude was no different between girls and boys.

Overall, boys had more advanced gross motor skills and higher activity levels than girls, independent of true- or false-negative status.

In post hoc analyses, boys with false-negative results were rated as more shy than boys with true-negative results. Girls with false negatives were rated as less shy than girls with true negatives and boys with false negatives. Ratings of emotionality and activity did not differ among the children with true or false negatives.

The authors speculated that girls with false negatives may have “somewhat lower levels of social fearfulness or lower inhibitory control, compared with boys.”

The authors also suggested possible reasons for the false negatives, including parents’ difficulty in matching behaviors described in the M-CHAT with their children’s behaviors and the lack of graded responses on the M-CHAT, which may influence parents’ responses.

By comparison, the Ages and Stages Questionnaire “gives parents the opportunity to express that the children exhibit skills occasionally albeit inconsistently, which may allow them to express their concerns and perceptions in a more graded manner,” the authors wrote.

Another possible reason for false negatives, the authors suggested, is that symptoms in those with autism spectrum disorder may manifest differently in early childhood, partly depending on the level of the child’s verbal and nonverbal skills.

“We believe that our results contribute, at a fundamental level, to our understanding of early screening for ASD, and we highlight the discrepancy between hard cutoff criteria for autism and the social-communicative, developmental, and temperamental signatures of emerging or subthreshold autism phenotypes,” the authors wrote. They noted a need for screens that take into account temperament and verbal and nonverbal skill levels.

The research was funded by the Norwegian Ministry of Health and Care Services, the Norwegian Ministry of Education and Research, the Research Council of Norway and Functional Genomics in Norway, the National Institute of Neurological Disorders and Stroke and the National Institute of Environmental Health Sciences. Dr Hornig coinvented an intestinal microbiome biomarker for autism which has patents assigned to Columbia University.

SOURCE: Øien RA et al. Pediatrics. 2018;141(6):e20173596.

Rajiv Datta, MD, FACS, FRCS, chief of surgery, South Nassau Communities Hospital, Oceanside, NY, recently received South Nassau’s 2017 Mary Pearson Award. The award is presented annually to an individual for extraordinary effort and individual contributions that advance the hospital’s mission to provide compassionate care and standard-setting health care services.

Dr. Datta, also medical director, Gertrude & Louis Feil Cancer Center, Valley Stream, NY, and director, division of surgical oncology and head and neck surgery, joined South Nassau in 2001 and has since gained an international reputation for leadership and surgical innovation. His leadership allowed Gertrude & Louis Feil Cancer Center to be equipped with cutting-edge cancer treatment technology, and colleagues and patients recognize Dr. Datta for his surgical skill and compassionate demeanor.

The SESC noted that Dr. Greene earned the organization’s Distinguished Service Award for his contributions to the field of surgery, which significantly added to the SESC’s mission of supporting professional development and educational opportunities.

Rajiv Datta, MD, FACS, FRCS, chief of surgery, South Nassau Communities Hospital, Oceanside, NY, recently received South Nassau’s 2017 Mary Pearson Award. The award is presented annually to an individual for extraordinary effort and individual contributions that advance the hospital’s mission to provide compassionate care and standard-setting health care services.

Dr. Datta, also medical director, Gertrude & Louis Feil Cancer Center, Valley Stream, NY, and director, division of surgical oncology and head and neck surgery, joined South Nassau in 2001 and has since gained an international reputation for leadership and surgical innovation. His leadership allowed Gertrude & Louis Feil Cancer Center to be equipped with cutting-edge cancer treatment technology, and colleagues and patients recognize Dr. Datta for his surgical skill and compassionate demeanor.

The SESC noted that Dr. Greene earned the organization’s Distinguished Service Award for his contributions to the field of surgery, which significantly added to the SESC’s mission of supporting professional development and educational opportunities.

Rajiv Datta, MD, FACS, FRCS, chief of surgery, South Nassau Communities Hospital, Oceanside, NY, recently received South Nassau’s 2017 Mary Pearson Award. The award is presented annually to an individual for extraordinary effort and individual contributions that advance the hospital’s mission to provide compassionate care and standard-setting health care services.

Dr. Datta, also medical director, Gertrude & Louis Feil Cancer Center, Valley Stream, NY, and director, division of surgical oncology and head and neck surgery, joined South Nassau in 2001 and has since gained an international reputation for leadership and surgical innovation. His leadership allowed Gertrude & Louis Feil Cancer Center to be equipped with cutting-edge cancer treatment technology, and colleagues and patients recognize Dr. Datta for his surgical skill and compassionate demeanor.

The SESC noted that Dr. Greene earned the organization’s Distinguished Service Award for his contributions to the field of surgery, which significantly added to the SESC’s mission of supporting professional development and educational opportunities.

The American College of Surgeons (ACS) Division of Advocacy and Health Policy (DAHP) seeks feedback from Fellows about existing Medicare documentation requirements that are unnecessary, difficult to understand, complicate the submission of claims, and delay patient care. The DAHP will use surgeon input to establish policy recommendations for regulatory relief under the Centers for Medicare & Medicaid Services (CMS) Documentation Requirements Simplification (DRS) Initiative. The key objectives of the DRS Initiative are to eliminate documentation requirements that are no longer needed and to simplify the remaining documentation requirements to reduce improper payments and appeals. To share your story about Medicare documentation burdens, contact Lauren Foe, ACS Regulatory Associate, at [email protected].

The American College of Surgeons (ACS) Division of Advocacy and Health Policy (DAHP) seeks feedback from Fellows about existing Medicare documentation requirements that are unnecessary, difficult to understand, complicate the submission of claims, and delay patient care. The DAHP will use surgeon input to establish policy recommendations for regulatory relief under the Centers for Medicare & Medicaid Services (CMS) Documentation Requirements Simplification (DRS) Initiative. The key objectives of the DRS Initiative are to eliminate documentation requirements that are no longer needed and to simplify the remaining documentation requirements to reduce improper payments and appeals. To share your story about Medicare documentation burdens, contact Lauren Foe, ACS Regulatory Associate, at [email protected].

The American College of Surgeons (ACS) Division of Advocacy and Health Policy (DAHP) seeks feedback from Fellows about existing Medicare documentation requirements that are unnecessary, difficult to understand, complicate the submission of claims, and delay patient care. The DAHP will use surgeon input to establish policy recommendations for regulatory relief under the Centers for Medicare & Medicaid Services (CMS) Documentation Requirements Simplification (DRS) Initiative. The key objectives of the DRS Initiative are to eliminate documentation requirements that are no longer needed and to simplify the remaining documentation requirements to reduce improper payments and appeals. To share your story about Medicare documentation burdens, contact Lauren Foe, ACS Regulatory Associate, at [email protected].