User login
AGA tools help GIs manage patients with obesity
Patients with obesity need a multidisciplinary approach to achieve a healthy weight. AGA understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity led by gastroenterologists.
To watch
AGA Solutions to Successful Obesity Program Integration: Andres Acosta, MD, PhD, assistant professor in medicine, clinical enteric neuroscience translational and epidemiological research, division of gastroenterology and hepatology, Mayo Clinic, Rochester, MN, and Sarah Streett, MD, AGAF, clinical associate professor and director of IBD, Stanford (Calif.) University, discuss the AGA Obesity Guide and how GIs can begin to implement the program in their practices. Watch the on-demand webinar in the AGA Community resource library.
To read
POWER: Practice Guide on Obesity and Weight Management, Education and Resources: This practice guide on obesity and weight management will help you develop a multidisciplinary team and obesity care model for your practice.
Episode-of-Care Framework for the Management of Obesity: Moving toward high-value, high-quality care – AGA established an obesity episode-of-care model to develop a framework to support value-based management of patients with obesity, focusing on the provision of nonsurgical and endoscopic services.
These resources are available at www.gastro.org/obesity.
To discuss
Visit the AGA Community to join the discussion on managing your patient with obesity.
Patients with obesity need a multidisciplinary approach to achieve a healthy weight. AGA understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity led by gastroenterologists.
To watch
AGA Solutions to Successful Obesity Program Integration: Andres Acosta, MD, PhD, assistant professor in medicine, clinical enteric neuroscience translational and epidemiological research, division of gastroenterology and hepatology, Mayo Clinic, Rochester, MN, and Sarah Streett, MD, AGAF, clinical associate professor and director of IBD, Stanford (Calif.) University, discuss the AGA Obesity Guide and how GIs can begin to implement the program in their practices. Watch the on-demand webinar in the AGA Community resource library.
To read
POWER: Practice Guide on Obesity and Weight Management, Education and Resources: This practice guide on obesity and weight management will help you develop a multidisciplinary team and obesity care model for your practice.
Episode-of-Care Framework for the Management of Obesity: Moving toward high-value, high-quality care – AGA established an obesity episode-of-care model to develop a framework to support value-based management of patients with obesity, focusing on the provision of nonsurgical and endoscopic services.
These resources are available at www.gastro.org/obesity.
To discuss
Visit the AGA Community to join the discussion on managing your patient with obesity.
Patients with obesity need a multidisciplinary approach to achieve a healthy weight. AGA understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity led by gastroenterologists.
To watch
AGA Solutions to Successful Obesity Program Integration: Andres Acosta, MD, PhD, assistant professor in medicine, clinical enteric neuroscience translational and epidemiological research, division of gastroenterology and hepatology, Mayo Clinic, Rochester, MN, and Sarah Streett, MD, AGAF, clinical associate professor and director of IBD, Stanford (Calif.) University, discuss the AGA Obesity Guide and how GIs can begin to implement the program in their practices. Watch the on-demand webinar in the AGA Community resource library.
To read
POWER: Practice Guide on Obesity and Weight Management, Education and Resources: This practice guide on obesity and weight management will help you develop a multidisciplinary team and obesity care model for your practice.
Episode-of-Care Framework for the Management of Obesity: Moving toward high-value, high-quality care – AGA established an obesity episode-of-care model to develop a framework to support value-based management of patients with obesity, focusing on the provision of nonsurgical and endoscopic services.
These resources are available at www.gastro.org/obesity.
To discuss
Visit the AGA Community to join the discussion on managing your patient with obesity.
DTC genetic health risk tests: Beware
The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.
As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.
The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.
As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.
The Food and Drug Administration recently authorized 23andMe to provide consumers with results of germline DNA sequence variants associated with risk for 10 health conditions, among them hereditary hemochromatosis, alpha-1 antitrypsin deficiency, celiac disease, Alzheimer’s disease, and Parkinson’s disease. After they submit a saliva sample and pay a test fee, customers ordering the online test will receive a report delineating their ancestry markers and informing them whether they carry any of the genetic variants associated with selected health risks included on the targeted DNA sequencing panel.
As more consumers partake in “recreational genomic testing,” clinicians should understand the limitations of DTC genetic tests and should be prepared to discuss with patients why these should not supersede clinical diagnostic evaluations.
Dr. Stoffel is a gastroenterologist, assistant professor of internal medicine, and director of the cancer genetics clinic at the University of Michigan, Ann Arbor. She has no disclosures.
Revaccinate HIV-infected teens with hepatitis B vaccine
Consider revaccinating all perinatally HIV-infected adolescents who did not initiate highly active antiretroviral therapy (HAART) at the time of initial infant hepatitis B virus (HBV) vaccination, with a three-dose HBV schedule, recommended researchers at Mahidol University, Bangkok, in a recent study.
In a prospective study from March 2012 to March 2014 ultimately involving 162 perinatally HIV-infected adolescents with immune reconstitution, only 3.6% were receiving HAART at the time of initial infant HBV vaccination and 96.3% had undetectable antihepatitis B surface antibodies (anti-HBs) at baseline. Adolescents with breakthrough HBV infection had been excluded from the cohort.
In a multivariate analysis, there was no independent factor that was associated with the presence of immune memory defined as anti-HBs greater than or equal to 100 mIU/mL, wrote lead researcher Keswadee Lapphra, MD, and her associates.
In a previous study, 71% of three-dose revaccinated persons retained protective antibodies against HBV at 3-year follow-up; this was a similar rate to that reported in healthy HIV-infected children after their infant primary HBV series (Vaccine. 2011 May 23;29[23]:3977-81), they said.
Read more at (Ped Inf Dis J. 2017. doi: 10.1097/inf.0000000000001613).
Consider revaccinating all perinatally HIV-infected adolescents who did not initiate highly active antiretroviral therapy (HAART) at the time of initial infant hepatitis B virus (HBV) vaccination, with a three-dose HBV schedule, recommended researchers at Mahidol University, Bangkok, in a recent study.
In a prospective study from March 2012 to March 2014 ultimately involving 162 perinatally HIV-infected adolescents with immune reconstitution, only 3.6% were receiving HAART at the time of initial infant HBV vaccination and 96.3% had undetectable antihepatitis B surface antibodies (anti-HBs) at baseline. Adolescents with breakthrough HBV infection had been excluded from the cohort.
In a multivariate analysis, there was no independent factor that was associated with the presence of immune memory defined as anti-HBs greater than or equal to 100 mIU/mL, wrote lead researcher Keswadee Lapphra, MD, and her associates.
In a previous study, 71% of three-dose revaccinated persons retained protective antibodies against HBV at 3-year follow-up; this was a similar rate to that reported in healthy HIV-infected children after their infant primary HBV series (Vaccine. 2011 May 23;29[23]:3977-81), they said.
Read more at (Ped Inf Dis J. 2017. doi: 10.1097/inf.0000000000001613).
Consider revaccinating all perinatally HIV-infected adolescents who did not initiate highly active antiretroviral therapy (HAART) at the time of initial infant hepatitis B virus (HBV) vaccination, with a three-dose HBV schedule, recommended researchers at Mahidol University, Bangkok, in a recent study.
In a prospective study from March 2012 to March 2014 ultimately involving 162 perinatally HIV-infected adolescents with immune reconstitution, only 3.6% were receiving HAART at the time of initial infant HBV vaccination and 96.3% had undetectable antihepatitis B surface antibodies (anti-HBs) at baseline. Adolescents with breakthrough HBV infection had been excluded from the cohort.
In a multivariate analysis, there was no independent factor that was associated with the presence of immune memory defined as anti-HBs greater than or equal to 100 mIU/mL, wrote lead researcher Keswadee Lapphra, MD, and her associates.
In a previous study, 71% of three-dose revaccinated persons retained protective antibodies against HBV at 3-year follow-up; this was a similar rate to that reported in healthy HIV-infected children after their infant primary HBV series (Vaccine. 2011 May 23;29[23]:3977-81), they said.
Read more at (Ped Inf Dis J. 2017. doi: 10.1097/inf.0000000000001613).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
ASBS annual meeting to explore treatment controversies
ACS Surgery News will be in Las Vegas this week at the annual meeting of the American Society of Breast Surgeons reporting on the latest in multidisciplinary management of benign and not-so-benign breast disease. Our reporters will cover controversies in neoadjuvant therapy, including managing axilla and skipping surgery with biopsy proven pathological complete response (pCR), as well as the use of axillary ultrasound on a clinically negative axilla, and what to do for in situ carcinoma and borderline cases. Coverage will also include the latest updates in high-risk and genetic predisposition, breast cancer subtypes, lymphedema, and recurrent and metastatic breast cancer, and guidance for coding and reimbursement.
Highly anticipated presentations include:
• Many Women are Choosing Unnecessarily Radical Surgeries for Early-Stage Cancer
• Debunking the Myth of Lymphedema Risk
• Aggressive Inflammatory Breast Cancer Treatment Yields Low Local/Regional Recurrence
Our team will provide daily coverage, beginning Thursday, April 27.
ACS Surgery News will be in Las Vegas this week at the annual meeting of the American Society of Breast Surgeons reporting on the latest in multidisciplinary management of benign and not-so-benign breast disease. Our reporters will cover controversies in neoadjuvant therapy, including managing axilla and skipping surgery with biopsy proven pathological complete response (pCR), as well as the use of axillary ultrasound on a clinically negative axilla, and what to do for in situ carcinoma and borderline cases. Coverage will also include the latest updates in high-risk and genetic predisposition, breast cancer subtypes, lymphedema, and recurrent and metastatic breast cancer, and guidance for coding and reimbursement.
Highly anticipated presentations include:
• Many Women are Choosing Unnecessarily Radical Surgeries for Early-Stage Cancer
• Debunking the Myth of Lymphedema Risk
• Aggressive Inflammatory Breast Cancer Treatment Yields Low Local/Regional Recurrence
Our team will provide daily coverage, beginning Thursday, April 27.
ACS Surgery News will be in Las Vegas this week at the annual meeting of the American Society of Breast Surgeons reporting on the latest in multidisciplinary management of benign and not-so-benign breast disease. Our reporters will cover controversies in neoadjuvant therapy, including managing axilla and skipping surgery with biopsy proven pathological complete response (pCR), as well as the use of axillary ultrasound on a clinically negative axilla, and what to do for in situ carcinoma and borderline cases. Coverage will also include the latest updates in high-risk and genetic predisposition, breast cancer subtypes, lymphedema, and recurrent and metastatic breast cancer, and guidance for coding and reimbursement.
Highly anticipated presentations include:
• Many Women are Choosing Unnecessarily Radical Surgeries for Early-Stage Cancer
• Debunking the Myth of Lymphedema Risk
• Aggressive Inflammatory Breast Cancer Treatment Yields Low Local/Regional Recurrence
Our team will provide daily coverage, beginning Thursday, April 27.
FROM ASBS 2017
Reflectance Confocal Microscopy Videomosaic of Melanoma In Situ
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Optimum antithymocyte globulin exposure after HTC affects survival
Optimum antithymocyte globulin exposure after allogeneic hemopoietic cell transplantation (HTC) is associated with a higher probability of survival as a result of reductions in transplant-related and relapse-related deaths, based on findings from a retrospective multicenter cohort study.
The findings come from a pharmacokinetic-pharmacodynamic analysis of data from 146 patients with acute lymphoid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. All were receiving their first T cell–repleted allogeneic peripheral blood stem cell HCT with antithymocyte globulin (ATG) as part of their nonmyeloablative conditioning regimen. Based on hazard ratios for overall survival, nonrelapse mortality, and relapse-related mortality, the optimum range of ATG exposure was 60-95 arbitrary units per day/mL, Rick Admiraal, MD, of the University Medical Centre Utrecht, Netherlands, and his colleagues reported in the Lancet Haematology (Lancet Haematol. 2017 Apr;4[4]:e183-91).
The estimated 5-year survival was significantly greater with optimum ATG exposure than with below-optimum exposure (69% vs. 32%; hazard ratio, 2.41) or with above-optimum exposure (69% vs. 48%; hazard ratio, 2.11).
Optimum ATG exposure also was associated with a greater likelihood of event-free survival: The hazard ratio was 2.54 for those with below-optimum exposure and 1.83 for those with above-optimum exposure, the researchers said. Further, above-optimum exposure was associated with higher relapse-related mortality (hazard ratio, 2.66). Below-optimum exposure was associated with higher non-relapse mortality (hazard ratio, 4.36) as well as with a higher risk for grade 3-4 acute graft-versus-host disease (hazard ratio, 3.09), but not for chronic graft-versus-host disease (hazard ratio, 2.38).
Optimum target attainment was better with modeled dosing based on absolute lymphocyte counts than with weight-based dosing, the authors said.
The findings underscore the importance of optimum ATG dosing, as “survival after HCT is highly affected by ATG exposure after HCT,” and they suggest that survival chances may be improved with individualized dosing based on lymphocyte counts–a finding that requires assessment in a prospective study, they concluded.
This study was funded by the Dutch Organization for Scientific Research and the Queen Wilhelmina Fund for Cancer Research. Dr. Admiraal reported having no relevant disclosures.
The study by Dr. Admiraal and his associates introduces important concepts regarding ATG dosing, but the suggestion that dosing should be individualized based on lymphocyte count and should target the area under the time-versus-thymoglobulin-concentration curve of 60-95 arbitrary units per day/mL after HCT should not yet become the standard of care.
“As the authors correctly point out, first a prospective study is needed,” Dr. Storek wrote.
However, even if such a study confirms this approach – which the authors previously showed to be of benefit in children – it would apply only to the setting in which it was developed. The problem is that there are numerous HCT settings, each requiring a different dose. Further, there is no universally accepted assay for measuring thymoglobulin concentrations, he noted.
“Following the seminal observations in the paper … much work remains to be done,” he wrote.
Jan Storek, MD, is with the University of Calgary (Alta.) and Alberta Health Services, Calgary. He made his comments in an editorial (Lancet Haematol. 2017 Apr;4[4]:e154-5) published with the study and reported having no disclosures.
The study by Dr. Admiraal and his associates introduces important concepts regarding ATG dosing, but the suggestion that dosing should be individualized based on lymphocyte count and should target the area under the time-versus-thymoglobulin-concentration curve of 60-95 arbitrary units per day/mL after HCT should not yet become the standard of care.
“As the authors correctly point out, first a prospective study is needed,” Dr. Storek wrote.
However, even if such a study confirms this approach – which the authors previously showed to be of benefit in children – it would apply only to the setting in which it was developed. The problem is that there are numerous HCT settings, each requiring a different dose. Further, there is no universally accepted assay for measuring thymoglobulin concentrations, he noted.
“Following the seminal observations in the paper … much work remains to be done,” he wrote.
Jan Storek, MD, is with the University of Calgary (Alta.) and Alberta Health Services, Calgary. He made his comments in an editorial (Lancet Haematol. 2017 Apr;4[4]:e154-5) published with the study and reported having no disclosures.
The study by Dr. Admiraal and his associates introduces important concepts regarding ATG dosing, but the suggestion that dosing should be individualized based on lymphocyte count and should target the area under the time-versus-thymoglobulin-concentration curve of 60-95 arbitrary units per day/mL after HCT should not yet become the standard of care.
“As the authors correctly point out, first a prospective study is needed,” Dr. Storek wrote.
However, even if such a study confirms this approach – which the authors previously showed to be of benefit in children – it would apply only to the setting in which it was developed. The problem is that there are numerous HCT settings, each requiring a different dose. Further, there is no universally accepted assay for measuring thymoglobulin concentrations, he noted.
“Following the seminal observations in the paper … much work remains to be done,” he wrote.
Jan Storek, MD, is with the University of Calgary (Alta.) and Alberta Health Services, Calgary. He made his comments in an editorial (Lancet Haematol. 2017 Apr;4[4]:e154-5) published with the study and reported having no disclosures.
Optimum antithymocyte globulin exposure after allogeneic hemopoietic cell transplantation (HTC) is associated with a higher probability of survival as a result of reductions in transplant-related and relapse-related deaths, based on findings from a retrospective multicenter cohort study.
The findings come from a pharmacokinetic-pharmacodynamic analysis of data from 146 patients with acute lymphoid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. All were receiving their first T cell–repleted allogeneic peripheral blood stem cell HCT with antithymocyte globulin (ATG) as part of their nonmyeloablative conditioning regimen. Based on hazard ratios for overall survival, nonrelapse mortality, and relapse-related mortality, the optimum range of ATG exposure was 60-95 arbitrary units per day/mL, Rick Admiraal, MD, of the University Medical Centre Utrecht, Netherlands, and his colleagues reported in the Lancet Haematology (Lancet Haematol. 2017 Apr;4[4]:e183-91).
The estimated 5-year survival was significantly greater with optimum ATG exposure than with below-optimum exposure (69% vs. 32%; hazard ratio, 2.41) or with above-optimum exposure (69% vs. 48%; hazard ratio, 2.11).
Optimum ATG exposure also was associated with a greater likelihood of event-free survival: The hazard ratio was 2.54 for those with below-optimum exposure and 1.83 for those with above-optimum exposure, the researchers said. Further, above-optimum exposure was associated with higher relapse-related mortality (hazard ratio, 2.66). Below-optimum exposure was associated with higher non-relapse mortality (hazard ratio, 4.36) as well as with a higher risk for grade 3-4 acute graft-versus-host disease (hazard ratio, 3.09), but not for chronic graft-versus-host disease (hazard ratio, 2.38).
Optimum target attainment was better with modeled dosing based on absolute lymphocyte counts than with weight-based dosing, the authors said.
The findings underscore the importance of optimum ATG dosing, as “survival after HCT is highly affected by ATG exposure after HCT,” and they suggest that survival chances may be improved with individualized dosing based on lymphocyte counts–a finding that requires assessment in a prospective study, they concluded.
This study was funded by the Dutch Organization for Scientific Research and the Queen Wilhelmina Fund for Cancer Research. Dr. Admiraal reported having no relevant disclosures.
Optimum antithymocyte globulin exposure after allogeneic hemopoietic cell transplantation (HTC) is associated with a higher probability of survival as a result of reductions in transplant-related and relapse-related deaths, based on findings from a retrospective multicenter cohort study.
The findings come from a pharmacokinetic-pharmacodynamic analysis of data from 146 patients with acute lymphoid leukemia, acute myeloid leukemia, or myelodysplastic syndrome. All were receiving their first T cell–repleted allogeneic peripheral blood stem cell HCT with antithymocyte globulin (ATG) as part of their nonmyeloablative conditioning regimen. Based on hazard ratios for overall survival, nonrelapse mortality, and relapse-related mortality, the optimum range of ATG exposure was 60-95 arbitrary units per day/mL, Rick Admiraal, MD, of the University Medical Centre Utrecht, Netherlands, and his colleagues reported in the Lancet Haematology (Lancet Haematol. 2017 Apr;4[4]:e183-91).
The estimated 5-year survival was significantly greater with optimum ATG exposure than with below-optimum exposure (69% vs. 32%; hazard ratio, 2.41) or with above-optimum exposure (69% vs. 48%; hazard ratio, 2.11).
Optimum ATG exposure also was associated with a greater likelihood of event-free survival: The hazard ratio was 2.54 for those with below-optimum exposure and 1.83 for those with above-optimum exposure, the researchers said. Further, above-optimum exposure was associated with higher relapse-related mortality (hazard ratio, 2.66). Below-optimum exposure was associated with higher non-relapse mortality (hazard ratio, 4.36) as well as with a higher risk for grade 3-4 acute graft-versus-host disease (hazard ratio, 3.09), but not for chronic graft-versus-host disease (hazard ratio, 2.38).
Optimum target attainment was better with modeled dosing based on absolute lymphocyte counts than with weight-based dosing, the authors said.
The findings underscore the importance of optimum ATG dosing, as “survival after HCT is highly affected by ATG exposure after HCT,” and they suggest that survival chances may be improved with individualized dosing based on lymphocyte counts–a finding that requires assessment in a prospective study, they concluded.
This study was funded by the Dutch Organization for Scientific Research and the Queen Wilhelmina Fund for Cancer Research. Dr. Admiraal reported having no relevant disclosures.
FROM THE LANCET HAEMATOLOGY
Key clinical point:
Major finding: The estimated 5-year survival with optimum ATG exposure was 69% vs. 32% and 48% with below- and above-optimum exposure (hazard ratios, 2.41 and 2.11, respectively).
Data source: A retrospective cohort study of 146 patients receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT.
Disclosures: This study was funded by the Dutch Organization for Scientific Research and the Queen Wilhelmina Fund for Cancer Research. Dr. Admiraal reported having no disclosures.
Extended maraviroc helps prevent graft-versus-host disease
ORLANDO – The use of the CCR5 antagonist maraviroc for 90 days is safe and effective for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic stem cell transplantation, according to findings from a phase II study.
An earlier study showed that CCR5 blockade using maraviroc for 33 days was associated with a low incidence of acute GVHD, as well as with absence of early liver and gut GVHD – although delayed severe cases of visceral GVHD still occurred.
The current study was performed because the prior findings raised concerns that brief blockade was insufficient for preventing GVHD over a longer period of time. The new findings show that an extended course may indeed provide additional benefits, Ran Reshef, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
In 37 high-risk patients who received allogeneic stem cell transplantation from unrelated donors using fludarabine/busulfan (Flu/Bu2) conditioning followed by peripheral blood stem cells, maraviroc was given at a dose of 300 mg twice daily, in addition to standard tacrolimus and methotrexate.
The 180-day rates of grade 2-4 and grade 3-4 acute GVHD (the primary endpoint of the study) in these patients were 27% and 5%, respectively. These rates were very similar to the 24% and 6% rates seen in the first study at 6 months after 30 days of maraviroc treatment, said Dr. Reshef of Columbia University Medical Center, New York.
The earlier results were “driven not so much by a reduction in the rates of skin GVHD, but by low rates of visceral GVHD of the gut and the liver – with a striking absence of gut and liver GVHD in the first 100 days,” he said.
Dr. Reshef also noted that the current study had a less favorable donor mix, as no matched related donors were included because of the earlier study’s very low rates of GVHD – with or without maraviroc – in those with related donors, who composed a third of donors.
Long-term follow-up of results from the earlier study, with comparison of a large contemporary control cohort, showed that “there is in fact an impact ... on grade 2-4 and grade 3-4 [GVHD], although the number of events is small, and the study was not powered enough to reach statistical significance,” Dr. Reshef said. The rates of chronic GVHD did not differ between the study subjects and contemporary controls, he noted.
At 100 days in the current study, there were no cases of liver GVHD, two cases of mild upper-GI GVHD, and one case of severe gut GVHD. At 1 year, the disease relapse rate was “fairly reasonable” at 30%, nonrelapse mortality was 12% with only one case of death from GVHD, and the incidence of chronic GVHD was 8%, which was significantly lower than in the prior study, he said.
The low rate of chronic GVHD led to a GVHD/relapse-free survival (GRFS) rate of 49%.
“To put this in context, the [Center for International Blood & Marrow Transplant Research] data for reduced-intensity transplants ... have shown 25% for acute myeloid leukemia and 12% for myelodysplastic syndrome,” he said. “So, we feel that these are by far improved numbers, compared with this benchmark.”
To determine which patients develop GVHD despite chemotaxis blockade and why, Dr. Reshef and his colleagues developed a pharmacodynamic assay to assess the activity of maraviroc in fresh blood samples. They found that those with insufficient CCR5 blockade on day 0 were those with higher incidence of severe acute GVHD, nonrelapse mortality, GRFS, and overall survival.
The investigators performed pharmacokinetic analysis using combined data from both trials to improve understanding of why some patients have insufficient CCR5 blockade. This showed significant variability in day 0 trough of maraviroc among patients (median of 65 ng/mL, range 12-316 ng/mL); levels above the median were associated with a significantly lower incidence of acute grade 2-4 GVHD and a trend toward improved GRFS.
These studies of maraviroc, which was originally developed for the treatment of HIV infection, were done to test the belief that blocking lymphocyte migration might prevent GVHD without interfering with graft-versus-tumor activity. Based on the earlier findings, Dr. Reshef and his colleagues hypothesized that treatment up to day 90 would decrease the rate to less than 30%, from a historical rate of 52%.
Patients in the study were high risk by virtue of age (median, 64 years), HLA matching (matched unrelated, 84%; mismatched unrelated, 16%), and comorbidities (comorbidity index greater than 2 in 49%). Underlying diseases were acute leukemia (78%), myelodysplastic syndrome (16%), and myeloproliferative neoplasm and cutaneous T-cell lymphomas (3% each).
At a median follow-up of 21 months, the 3-month course of maraviroc was well tolerated. Eight patients did not complete treatment because of disease relapse (five patients), skin reaction (one patient), early infection-related death (one patient), or poor tolerance of oral drugs (one patient). Neutrophil, platelet, and T-cell engraftment were similar to historical controls, and rates of infections were also similar, Dr Reshef noted.
“To conclude, an extended course of maraviroc up to day 90 is feasible and safe in the majority of patients,” he said. “This study confirms the effect of CCR5 blockade on visceral GVHD. I’m still awaiting a randomized study to confirm that further.
“A long course of maraviroc does not necessarily affect the rates of acute GVHD, but may help reduce chronic GVHD and improve GRFS,” Dr. Reshef said. “We should look further into the pharmacodynamic and pharmacokinetic variables.”
Dr. Reshef reported receiving research funding from Pfizer.
ORLANDO – The use of the CCR5 antagonist maraviroc for 90 days is safe and effective for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic stem cell transplantation, according to findings from a phase II study.
An earlier study showed that CCR5 blockade using maraviroc for 33 days was associated with a low incidence of acute GVHD, as well as with absence of early liver and gut GVHD – although delayed severe cases of visceral GVHD still occurred.
The current study was performed because the prior findings raised concerns that brief blockade was insufficient for preventing GVHD over a longer period of time. The new findings show that an extended course may indeed provide additional benefits, Ran Reshef, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
In 37 high-risk patients who received allogeneic stem cell transplantation from unrelated donors using fludarabine/busulfan (Flu/Bu2) conditioning followed by peripheral blood stem cells, maraviroc was given at a dose of 300 mg twice daily, in addition to standard tacrolimus and methotrexate.
The 180-day rates of grade 2-4 and grade 3-4 acute GVHD (the primary endpoint of the study) in these patients were 27% and 5%, respectively. These rates were very similar to the 24% and 6% rates seen in the first study at 6 months after 30 days of maraviroc treatment, said Dr. Reshef of Columbia University Medical Center, New York.
The earlier results were “driven not so much by a reduction in the rates of skin GVHD, but by low rates of visceral GVHD of the gut and the liver – with a striking absence of gut and liver GVHD in the first 100 days,” he said.
Dr. Reshef also noted that the current study had a less favorable donor mix, as no matched related donors were included because of the earlier study’s very low rates of GVHD – with or without maraviroc – in those with related donors, who composed a third of donors.
Long-term follow-up of results from the earlier study, with comparison of a large contemporary control cohort, showed that “there is in fact an impact ... on grade 2-4 and grade 3-4 [GVHD], although the number of events is small, and the study was not powered enough to reach statistical significance,” Dr. Reshef said. The rates of chronic GVHD did not differ between the study subjects and contemporary controls, he noted.
At 100 days in the current study, there were no cases of liver GVHD, two cases of mild upper-GI GVHD, and one case of severe gut GVHD. At 1 year, the disease relapse rate was “fairly reasonable” at 30%, nonrelapse mortality was 12% with only one case of death from GVHD, and the incidence of chronic GVHD was 8%, which was significantly lower than in the prior study, he said.
The low rate of chronic GVHD led to a GVHD/relapse-free survival (GRFS) rate of 49%.
“To put this in context, the [Center for International Blood & Marrow Transplant Research] data for reduced-intensity transplants ... have shown 25% for acute myeloid leukemia and 12% for myelodysplastic syndrome,” he said. “So, we feel that these are by far improved numbers, compared with this benchmark.”
To determine which patients develop GVHD despite chemotaxis blockade and why, Dr. Reshef and his colleagues developed a pharmacodynamic assay to assess the activity of maraviroc in fresh blood samples. They found that those with insufficient CCR5 blockade on day 0 were those with higher incidence of severe acute GVHD, nonrelapse mortality, GRFS, and overall survival.
The investigators performed pharmacokinetic analysis using combined data from both trials to improve understanding of why some patients have insufficient CCR5 blockade. This showed significant variability in day 0 trough of maraviroc among patients (median of 65 ng/mL, range 12-316 ng/mL); levels above the median were associated with a significantly lower incidence of acute grade 2-4 GVHD and a trend toward improved GRFS.
These studies of maraviroc, which was originally developed for the treatment of HIV infection, were done to test the belief that blocking lymphocyte migration might prevent GVHD without interfering with graft-versus-tumor activity. Based on the earlier findings, Dr. Reshef and his colleagues hypothesized that treatment up to day 90 would decrease the rate to less than 30%, from a historical rate of 52%.
Patients in the study were high risk by virtue of age (median, 64 years), HLA matching (matched unrelated, 84%; mismatched unrelated, 16%), and comorbidities (comorbidity index greater than 2 in 49%). Underlying diseases were acute leukemia (78%), myelodysplastic syndrome (16%), and myeloproliferative neoplasm and cutaneous T-cell lymphomas (3% each).
At a median follow-up of 21 months, the 3-month course of maraviroc was well tolerated. Eight patients did not complete treatment because of disease relapse (five patients), skin reaction (one patient), early infection-related death (one patient), or poor tolerance of oral drugs (one patient). Neutrophil, platelet, and T-cell engraftment were similar to historical controls, and rates of infections were also similar, Dr Reshef noted.
“To conclude, an extended course of maraviroc up to day 90 is feasible and safe in the majority of patients,” he said. “This study confirms the effect of CCR5 blockade on visceral GVHD. I’m still awaiting a randomized study to confirm that further.
“A long course of maraviroc does not necessarily affect the rates of acute GVHD, but may help reduce chronic GVHD and improve GRFS,” Dr. Reshef said. “We should look further into the pharmacodynamic and pharmacokinetic variables.”
Dr. Reshef reported receiving research funding from Pfizer.
ORLANDO – The use of the CCR5 antagonist maraviroc for 90 days is safe and effective for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic stem cell transplantation, according to findings from a phase II study.
An earlier study showed that CCR5 blockade using maraviroc for 33 days was associated with a low incidence of acute GVHD, as well as with absence of early liver and gut GVHD – although delayed severe cases of visceral GVHD still occurred.
The current study was performed because the prior findings raised concerns that brief blockade was insufficient for preventing GVHD over a longer period of time. The new findings show that an extended course may indeed provide additional benefits, Ran Reshef, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
In 37 high-risk patients who received allogeneic stem cell transplantation from unrelated donors using fludarabine/busulfan (Flu/Bu2) conditioning followed by peripheral blood stem cells, maraviroc was given at a dose of 300 mg twice daily, in addition to standard tacrolimus and methotrexate.
The 180-day rates of grade 2-4 and grade 3-4 acute GVHD (the primary endpoint of the study) in these patients were 27% and 5%, respectively. These rates were very similar to the 24% and 6% rates seen in the first study at 6 months after 30 days of maraviroc treatment, said Dr. Reshef of Columbia University Medical Center, New York.
The earlier results were “driven not so much by a reduction in the rates of skin GVHD, but by low rates of visceral GVHD of the gut and the liver – with a striking absence of gut and liver GVHD in the first 100 days,” he said.
Dr. Reshef also noted that the current study had a less favorable donor mix, as no matched related donors were included because of the earlier study’s very low rates of GVHD – with or without maraviroc – in those with related donors, who composed a third of donors.
Long-term follow-up of results from the earlier study, with comparison of a large contemporary control cohort, showed that “there is in fact an impact ... on grade 2-4 and grade 3-4 [GVHD], although the number of events is small, and the study was not powered enough to reach statistical significance,” Dr. Reshef said. The rates of chronic GVHD did not differ between the study subjects and contemporary controls, he noted.
At 100 days in the current study, there were no cases of liver GVHD, two cases of mild upper-GI GVHD, and one case of severe gut GVHD. At 1 year, the disease relapse rate was “fairly reasonable” at 30%, nonrelapse mortality was 12% with only one case of death from GVHD, and the incidence of chronic GVHD was 8%, which was significantly lower than in the prior study, he said.
The low rate of chronic GVHD led to a GVHD/relapse-free survival (GRFS) rate of 49%.
“To put this in context, the [Center for International Blood & Marrow Transplant Research] data for reduced-intensity transplants ... have shown 25% for acute myeloid leukemia and 12% for myelodysplastic syndrome,” he said. “So, we feel that these are by far improved numbers, compared with this benchmark.”
To determine which patients develop GVHD despite chemotaxis blockade and why, Dr. Reshef and his colleagues developed a pharmacodynamic assay to assess the activity of maraviroc in fresh blood samples. They found that those with insufficient CCR5 blockade on day 0 were those with higher incidence of severe acute GVHD, nonrelapse mortality, GRFS, and overall survival.
The investigators performed pharmacokinetic analysis using combined data from both trials to improve understanding of why some patients have insufficient CCR5 blockade. This showed significant variability in day 0 trough of maraviroc among patients (median of 65 ng/mL, range 12-316 ng/mL); levels above the median were associated with a significantly lower incidence of acute grade 2-4 GVHD and a trend toward improved GRFS.
These studies of maraviroc, which was originally developed for the treatment of HIV infection, were done to test the belief that blocking lymphocyte migration might prevent GVHD without interfering with graft-versus-tumor activity. Based on the earlier findings, Dr. Reshef and his colleagues hypothesized that treatment up to day 90 would decrease the rate to less than 30%, from a historical rate of 52%.
Patients in the study were high risk by virtue of age (median, 64 years), HLA matching (matched unrelated, 84%; mismatched unrelated, 16%), and comorbidities (comorbidity index greater than 2 in 49%). Underlying diseases were acute leukemia (78%), myelodysplastic syndrome (16%), and myeloproliferative neoplasm and cutaneous T-cell lymphomas (3% each).
At a median follow-up of 21 months, the 3-month course of maraviroc was well tolerated. Eight patients did not complete treatment because of disease relapse (five patients), skin reaction (one patient), early infection-related death (one patient), or poor tolerance of oral drugs (one patient). Neutrophil, platelet, and T-cell engraftment were similar to historical controls, and rates of infections were also similar, Dr Reshef noted.
“To conclude, an extended course of maraviroc up to day 90 is feasible and safe in the majority of patients,” he said. “This study confirms the effect of CCR5 blockade on visceral GVHD. I’m still awaiting a randomized study to confirm that further.
“A long course of maraviroc does not necessarily affect the rates of acute GVHD, but may help reduce chronic GVHD and improve GRFS,” Dr. Reshef said. “We should look further into the pharmacodynamic and pharmacokinetic variables.”
Dr. Reshef reported receiving research funding from Pfizer.
AT THE 2017 BMT TANDEM MEETINGS
Key clinical point:
Major finding: The 180-day rates of grade 2-4 and grade 3-4 acute GVHD were 27% and 5%, respectively.
Data source: A phase II study of 37 patients.
Disclosures: Dr. Reshef reported receiving research funding from Pfizer.
Can public reporting improve pediatric heart surgery?
Public reporting of cardiac surgery outcomes has been a disruptive force in cardiology, and especially daunting in pediatric cardiac surgery because of low case volumes and rare mortality. To ensure that public reporting achieves its original goals – providing transparency to the patient care process, holding providers accountable, informing decision making for health care consumers, reducing costs, encouraging more efficient use of health system resources, and improving patient care and outcomes – further study that includes use of appropriate risk adjustment is needed, according to commentaries in the April issue of the Journal of Thoracic and Cardiovascular Surgery.
The journal asked two groups to provide perspective on a study Adam D. DeVore, MD, of Duke University in Durham, N.C., and his coauthors published last year (J Am Coll Cardiol. 2016 Mar 1;67:963-72). The study analyzed Medicare claims data from 2006 to 2012 for 37,829 hospitalizations for heart attack, 100,189 for heart failure (HF), and 79,076 for pneumonia. Dr. DeVore and his colleagues found readmission rates for the three conditions did not significantly improve after public reporting protocols were implemented in 2009. However, the study did show a significant decrease in ED visits and observation stays for those with HF: from 2.3% to –0.8% for the former (P = .007); and from 15% to 4% for the latter (P = .04).
• The metrics must be accurate, reliably discern hospital quality, and account for high-risk cases without penalizing hospitals. “In pediatric cardiac surgery, this can be particularly challenging, owing to the very wide heterogeneity of disease and variability in case mix and volumes across centers,” Dr. Gaynor and his coauthors wrote. While methodology for case mix and patient characteristics have improved in recent years, further improvement is needed.
• Metrics must be clearly reported and easy for stakeholders to interpret. “This is critical if the data are to be used to steer patients toward higher-performing centers and/or to provide incentives for hospitals with lower performance to make improvements,” the researchers said.
• Regional reporting or a methodology that indicates where a hospital ranks within larger categories deserve further investigation as tools to help families choose a high-performing center, “ideally based on geography and on the particular type and complexity of disease,” Dr. Gaynor and his coauthors stated (J Thorac Cardiovasc Surg. 2017 Apr;153:904-7).
• Indirect standardization, a statistical methodology used to calculate risk-adjusted performance, could help consumers to interpret hospital performance more easily. This methodology might help classify a hospital with a low-complexity population as a high performer. “Developing better methods to convey this information to consumers is vital,” according to the researchers.
The perspective acknowledged several reports of an unintended consequence of public reporting: surgeons and centers avoiding higher-risk cases to skew their performance scores higher, thus restricting access to care. However, in a separate perspective on Dr. DeVore’s study, James S. Tweddell, MD, of Cincinnati Children’s Hospital Medical Center, and his coauthors, questioned the quality of the evidence on which Dr. Gaynor and his colleagues based their conclusion of risk aversion and limited access to care: a newspaper report from the United Kingdom.
Dr. Tweddell and his coauthors noted, “The predominance of data suggest an overall beneficial impact of public reporting.” They cited a trial that showed a decrease in heart attack–related deaths after public reporting had been implemented (JAMA. 2009 Dec 2;302:2330-7); a 2012 Agency for Healthcare Research and Quality systemic review (Evidence Report No. 208) that showed that research on harm is limited, and most studies do not confirm potential harm; and a meta-analysis that found a 15% reduction in adverse events associated with public reporting (BMC Health Serv Res. 2016;16:296).
“Appropriate risk adjustment is critical to achieve effective and fair transparency, but there is little objective data of harm associated with public reporting,” Dr. Tweddell and his coauthors concluded. While examination of public reporting must continue, they said, “these efforts are likely to result in minor course changes and the effort to inform and educate our patients and their families must continue.”
Ds. Gaynor, Dr. Tweddell, and their coauthors reported having no financial disclosures.
Public reporting of cardiac surgery outcomes has been a disruptive force in cardiology, and especially daunting in pediatric cardiac surgery because of low case volumes and rare mortality. To ensure that public reporting achieves its original goals – providing transparency to the patient care process, holding providers accountable, informing decision making for health care consumers, reducing costs, encouraging more efficient use of health system resources, and improving patient care and outcomes – further study that includes use of appropriate risk adjustment is needed, according to commentaries in the April issue of the Journal of Thoracic and Cardiovascular Surgery.
The journal asked two groups to provide perspective on a study Adam D. DeVore, MD, of Duke University in Durham, N.C., and his coauthors published last year (J Am Coll Cardiol. 2016 Mar 1;67:963-72). The study analyzed Medicare claims data from 2006 to 2012 for 37,829 hospitalizations for heart attack, 100,189 for heart failure (HF), and 79,076 for pneumonia. Dr. DeVore and his colleagues found readmission rates for the three conditions did not significantly improve after public reporting protocols were implemented in 2009. However, the study did show a significant decrease in ED visits and observation stays for those with HF: from 2.3% to –0.8% for the former (P = .007); and from 15% to 4% for the latter (P = .04).
• The metrics must be accurate, reliably discern hospital quality, and account for high-risk cases without penalizing hospitals. “In pediatric cardiac surgery, this can be particularly challenging, owing to the very wide heterogeneity of disease and variability in case mix and volumes across centers,” Dr. Gaynor and his coauthors wrote. While methodology for case mix and patient characteristics have improved in recent years, further improvement is needed.
• Metrics must be clearly reported and easy for stakeholders to interpret. “This is critical if the data are to be used to steer patients toward higher-performing centers and/or to provide incentives for hospitals with lower performance to make improvements,” the researchers said.
• Regional reporting or a methodology that indicates where a hospital ranks within larger categories deserve further investigation as tools to help families choose a high-performing center, “ideally based on geography and on the particular type and complexity of disease,” Dr. Gaynor and his coauthors stated (J Thorac Cardiovasc Surg. 2017 Apr;153:904-7).
• Indirect standardization, a statistical methodology used to calculate risk-adjusted performance, could help consumers to interpret hospital performance more easily. This methodology might help classify a hospital with a low-complexity population as a high performer. “Developing better methods to convey this information to consumers is vital,” according to the researchers.
The perspective acknowledged several reports of an unintended consequence of public reporting: surgeons and centers avoiding higher-risk cases to skew their performance scores higher, thus restricting access to care. However, in a separate perspective on Dr. DeVore’s study, James S. Tweddell, MD, of Cincinnati Children’s Hospital Medical Center, and his coauthors, questioned the quality of the evidence on which Dr. Gaynor and his colleagues based their conclusion of risk aversion and limited access to care: a newspaper report from the United Kingdom.
Dr. Tweddell and his coauthors noted, “The predominance of data suggest an overall beneficial impact of public reporting.” They cited a trial that showed a decrease in heart attack–related deaths after public reporting had been implemented (JAMA. 2009 Dec 2;302:2330-7); a 2012 Agency for Healthcare Research and Quality systemic review (Evidence Report No. 208) that showed that research on harm is limited, and most studies do not confirm potential harm; and a meta-analysis that found a 15% reduction in adverse events associated with public reporting (BMC Health Serv Res. 2016;16:296).
“Appropriate risk adjustment is critical to achieve effective and fair transparency, but there is little objective data of harm associated with public reporting,” Dr. Tweddell and his coauthors concluded. While examination of public reporting must continue, they said, “these efforts are likely to result in minor course changes and the effort to inform and educate our patients and their families must continue.”
Ds. Gaynor, Dr. Tweddell, and their coauthors reported having no financial disclosures.
Public reporting of cardiac surgery outcomes has been a disruptive force in cardiology, and especially daunting in pediatric cardiac surgery because of low case volumes and rare mortality. To ensure that public reporting achieves its original goals – providing transparency to the patient care process, holding providers accountable, informing decision making for health care consumers, reducing costs, encouraging more efficient use of health system resources, and improving patient care and outcomes – further study that includes use of appropriate risk adjustment is needed, according to commentaries in the April issue of the Journal of Thoracic and Cardiovascular Surgery.
The journal asked two groups to provide perspective on a study Adam D. DeVore, MD, of Duke University in Durham, N.C., and his coauthors published last year (J Am Coll Cardiol. 2016 Mar 1;67:963-72). The study analyzed Medicare claims data from 2006 to 2012 for 37,829 hospitalizations for heart attack, 100,189 for heart failure (HF), and 79,076 for pneumonia. Dr. DeVore and his colleagues found readmission rates for the three conditions did not significantly improve after public reporting protocols were implemented in 2009. However, the study did show a significant decrease in ED visits and observation stays for those with HF: from 2.3% to –0.8% for the former (P = .007); and from 15% to 4% for the latter (P = .04).
• The metrics must be accurate, reliably discern hospital quality, and account for high-risk cases without penalizing hospitals. “In pediatric cardiac surgery, this can be particularly challenging, owing to the very wide heterogeneity of disease and variability in case mix and volumes across centers,” Dr. Gaynor and his coauthors wrote. While methodology for case mix and patient characteristics have improved in recent years, further improvement is needed.
• Metrics must be clearly reported and easy for stakeholders to interpret. “This is critical if the data are to be used to steer patients toward higher-performing centers and/or to provide incentives for hospitals with lower performance to make improvements,” the researchers said.
• Regional reporting or a methodology that indicates where a hospital ranks within larger categories deserve further investigation as tools to help families choose a high-performing center, “ideally based on geography and on the particular type and complexity of disease,” Dr. Gaynor and his coauthors stated (J Thorac Cardiovasc Surg. 2017 Apr;153:904-7).
• Indirect standardization, a statistical methodology used to calculate risk-adjusted performance, could help consumers to interpret hospital performance more easily. This methodology might help classify a hospital with a low-complexity population as a high performer. “Developing better methods to convey this information to consumers is vital,” according to the researchers.
The perspective acknowledged several reports of an unintended consequence of public reporting: surgeons and centers avoiding higher-risk cases to skew their performance scores higher, thus restricting access to care. However, in a separate perspective on Dr. DeVore’s study, James S. Tweddell, MD, of Cincinnati Children’s Hospital Medical Center, and his coauthors, questioned the quality of the evidence on which Dr. Gaynor and his colleagues based their conclusion of risk aversion and limited access to care: a newspaper report from the United Kingdom.
Dr. Tweddell and his coauthors noted, “The predominance of data suggest an overall beneficial impact of public reporting.” They cited a trial that showed a decrease in heart attack–related deaths after public reporting had been implemented (JAMA. 2009 Dec 2;302:2330-7); a 2012 Agency for Healthcare Research and Quality systemic review (Evidence Report No. 208) that showed that research on harm is limited, and most studies do not confirm potential harm; and a meta-analysis that found a 15% reduction in adverse events associated with public reporting (BMC Health Serv Res. 2016;16:296).
“Appropriate risk adjustment is critical to achieve effective and fair transparency, but there is little objective data of harm associated with public reporting,” Dr. Tweddell and his coauthors concluded. While examination of public reporting must continue, they said, “these efforts are likely to result in minor course changes and the effort to inform and educate our patients and their families must continue.”
Ds. Gaynor, Dr. Tweddell, and their coauthors reported having no financial disclosures.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Public reporting of outcomes in cardiac surgery in children requires further investigation but has also been associated with improved outcomes.
Major finding: Emergency department visits for patients with heart failure declined from 2.3% before public reporting to –0.8% after implementation, and observation stays declined from 15.1% to 4.1%.
Data source: Analysis of Medicare claims data from 2006 to 2012 for 271,094 patients discharged after hospitalization for heart attack, heart failure or pneumonia.
Disclosures: Dr. Gaynor and Dr. Tweddell had no financial relationships to disclose.
CDC: Some Shigella strains show reduced ciprofloxacin susceptibility
The Centers for Disease Control and Prevention has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.
The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.
It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:
• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible – with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance regarding when patients may return to child care, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.
Additionally, the CDC noted that shigellosis is a nationally notifiable condition; all cases should be reported to the local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.
The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.
The Centers for Disease Control and Prevention has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.
The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.
It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:
• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible – with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance regarding when patients may return to child care, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.
Additionally, the CDC noted that shigellosis is a nationally notifiable condition; all cases should be reported to the local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.
The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.
The Centers for Disease Control and Prevention has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.
The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.
It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:
• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible – with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance regarding when patients may return to child care, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.
Additionally, the CDC noted that shigellosis is a nationally notifiable condition; all cases should be reported to the local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.
The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.
Survey insights: Unwrapping the compensation package
When approached for advice regarding the evaluation of job offers after completion of training, specific day-to-day duties (for example, shift length, teaching time, ICU coverage, and so on), and the overall gestalt of the interview experience, I find that location, lifestyle, and pay are the most consistent and common themes.
People often assume that pay is relatively straightforward, since it can be summarized in a number in the offer, whereas the other factors are harder to evaluate. However, it turns out pay is more complex. As a result, the last several State of Hospital Medicine reports have sought to evaluate compensation packages more thoroughly.
In 2016, the survey started including pay increases by years of experience, as well as CME dollars allotted per year per hospitalist. The goal was to gain deeper insight into the entire financial package, which is tied to a particular hospitalist job.
When looking at the 2014 and 2016 SHM survey results, there are several interesting findings. Base pay makes up the majority of earnings for all types of hospitalists (those seeing adults only, children only, and a mix of adults and children). In academic hospitalist groups, more of the total package of compensation comes from base pay, compared with nonacademic groups, where production and performance pay play a bigger role.
Of interest, despite the increased national attention on quality of care, productivity-based pay increased again (10.5%-14.7%), while performance-based pay (usually tied to quality and safety metrics) decreased (6.6%-5.7%) among groups serving adults. Consistent with prior trends for adults-only hospitalists, the Southern region of the country had the highest percentage of pay derived from productivity (18.8%), as well as of overall compensation in the 2016 report.
For hospitalists serving both adults and children, there was a smaller increase in pay derived from production (12.4%-13.2%), while pay derived from performance dropped more dramatically (8.9%-3.9%).
For hospitalists serving only children, the opposite occurred: Pay derived from production fell from 10.7% to 2.8%. While it is not yet clear why compensation, overall, is moving into closer alignment with productivity, rather than performance on quality and safety metrics, one hypothesis is that work relative value units used for calculating productivity are easier to tie to an individual hospitalist than are quality and safety outcomes.
Employee benefits, as previously defined, increased among hospitalists caring for adults only and those caring for adults and children, with a mean increase in both groups of $5,000. The most generous benefits were typically seen at university-based academic medical centers. Amongst adult-only hospitalists, academic groups offer benefits worth $8,000-$9,000 more per year than in nonacademic groups. Lower benefits were common among practices in the Eastern region and in groups with four or fewer full-time hospitalists. The 2016 survey data on CME dollars revealed a median of $3,000-$4,000 per year, with higher amounts provided in nonacademic groups.
Paid time off (PTO) from work is an ongoing topic of interest on venues such as HMX forum, and, in the surveys, PTO remained fairly consistent among groups caring for adults only and those caring for adults and children, with only 30%-40% of groups offering PTO. The number of PTO hours offered vary substantially, however, ranging from a mean of 126 hours up to 216.4 hours annually. Future analysis of PTO will benefit from a deeper understanding of how many hours equate to a shift (the practical definition of a “day off” for most hospitalists).
Finally, the 2016 survey asked about automatic pay increases based strictly on overall experience or length of employment with the group. Roughly one-fifth to one-third of groups provided some sort of salary increase based on experience in 2015. This practice was more common in the Southern region and in nonteaching hospitals. These data raise the complex topic of seniority among hospitalists and how to define it: years since completing training, years with a particular hospital or group, academic rank, leadership roles, other? Further, if seniority is not recognized in pay, how commonly are groups recognizing it in other ways, such as in preferences related to time on certain services, shift type, or vacation requests?
The expanded survey on hospitalist pay, in addition to the biannual comparison of prior data, will likely continue to add value in assessing and exploring the entire package of compensation. Additional topics of interest moving forward might include better understanding of parental leave, sick time, and the comparison between compensation packages for physician hospitalists and those for inpatient Nurse Practitioners and Physician Assistants. Stay tuned for the next report.
Dr. Anoff is associate professor of clinical practice, division of hospital medicine, department of medicine, University of Colorado at Denver, Aurora.
References
1. (2014). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2014.
2. (2016). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2016.
When approached for advice regarding the evaluation of job offers after completion of training, specific day-to-day duties (for example, shift length, teaching time, ICU coverage, and so on), and the overall gestalt of the interview experience, I find that location, lifestyle, and pay are the most consistent and common themes.
People often assume that pay is relatively straightforward, since it can be summarized in a number in the offer, whereas the other factors are harder to evaluate. However, it turns out pay is more complex. As a result, the last several State of Hospital Medicine reports have sought to evaluate compensation packages more thoroughly.
In 2016, the survey started including pay increases by years of experience, as well as CME dollars allotted per year per hospitalist. The goal was to gain deeper insight into the entire financial package, which is tied to a particular hospitalist job.
When looking at the 2014 and 2016 SHM survey results, there are several interesting findings. Base pay makes up the majority of earnings for all types of hospitalists (those seeing adults only, children only, and a mix of adults and children). In academic hospitalist groups, more of the total package of compensation comes from base pay, compared with nonacademic groups, where production and performance pay play a bigger role.
Of interest, despite the increased national attention on quality of care, productivity-based pay increased again (10.5%-14.7%), while performance-based pay (usually tied to quality and safety metrics) decreased (6.6%-5.7%) among groups serving adults. Consistent with prior trends for adults-only hospitalists, the Southern region of the country had the highest percentage of pay derived from productivity (18.8%), as well as of overall compensation in the 2016 report.
For hospitalists serving both adults and children, there was a smaller increase in pay derived from production (12.4%-13.2%), while pay derived from performance dropped more dramatically (8.9%-3.9%).
For hospitalists serving only children, the opposite occurred: Pay derived from production fell from 10.7% to 2.8%. While it is not yet clear why compensation, overall, is moving into closer alignment with productivity, rather than performance on quality and safety metrics, one hypothesis is that work relative value units used for calculating productivity are easier to tie to an individual hospitalist than are quality and safety outcomes.
Employee benefits, as previously defined, increased among hospitalists caring for adults only and those caring for adults and children, with a mean increase in both groups of $5,000. The most generous benefits were typically seen at university-based academic medical centers. Amongst adult-only hospitalists, academic groups offer benefits worth $8,000-$9,000 more per year than in nonacademic groups. Lower benefits were common among practices in the Eastern region and in groups with four or fewer full-time hospitalists. The 2016 survey data on CME dollars revealed a median of $3,000-$4,000 per year, with higher amounts provided in nonacademic groups.
Paid time off (PTO) from work is an ongoing topic of interest on venues such as HMX forum, and, in the surveys, PTO remained fairly consistent among groups caring for adults only and those caring for adults and children, with only 30%-40% of groups offering PTO. The number of PTO hours offered vary substantially, however, ranging from a mean of 126 hours up to 216.4 hours annually. Future analysis of PTO will benefit from a deeper understanding of how many hours equate to a shift (the practical definition of a “day off” for most hospitalists).
Finally, the 2016 survey asked about automatic pay increases based strictly on overall experience or length of employment with the group. Roughly one-fifth to one-third of groups provided some sort of salary increase based on experience in 2015. This practice was more common in the Southern region and in nonteaching hospitals. These data raise the complex topic of seniority among hospitalists and how to define it: years since completing training, years with a particular hospital or group, academic rank, leadership roles, other? Further, if seniority is not recognized in pay, how commonly are groups recognizing it in other ways, such as in preferences related to time on certain services, shift type, or vacation requests?
The expanded survey on hospitalist pay, in addition to the biannual comparison of prior data, will likely continue to add value in assessing and exploring the entire package of compensation. Additional topics of interest moving forward might include better understanding of parental leave, sick time, and the comparison between compensation packages for physician hospitalists and those for inpatient Nurse Practitioners and Physician Assistants. Stay tuned for the next report.
Dr. Anoff is associate professor of clinical practice, division of hospital medicine, department of medicine, University of Colorado at Denver, Aurora.
References
1. (2014). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2014.
2. (2016). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2016.
When approached for advice regarding the evaluation of job offers after completion of training, specific day-to-day duties (for example, shift length, teaching time, ICU coverage, and so on), and the overall gestalt of the interview experience, I find that location, lifestyle, and pay are the most consistent and common themes.
People often assume that pay is relatively straightforward, since it can be summarized in a number in the offer, whereas the other factors are harder to evaluate. However, it turns out pay is more complex. As a result, the last several State of Hospital Medicine reports have sought to evaluate compensation packages more thoroughly.
In 2016, the survey started including pay increases by years of experience, as well as CME dollars allotted per year per hospitalist. The goal was to gain deeper insight into the entire financial package, which is tied to a particular hospitalist job.
When looking at the 2014 and 2016 SHM survey results, there are several interesting findings. Base pay makes up the majority of earnings for all types of hospitalists (those seeing adults only, children only, and a mix of adults and children). In academic hospitalist groups, more of the total package of compensation comes from base pay, compared with nonacademic groups, where production and performance pay play a bigger role.
Of interest, despite the increased national attention on quality of care, productivity-based pay increased again (10.5%-14.7%), while performance-based pay (usually tied to quality and safety metrics) decreased (6.6%-5.7%) among groups serving adults. Consistent with prior trends for adults-only hospitalists, the Southern region of the country had the highest percentage of pay derived from productivity (18.8%), as well as of overall compensation in the 2016 report.
For hospitalists serving both adults and children, there was a smaller increase in pay derived from production (12.4%-13.2%), while pay derived from performance dropped more dramatically (8.9%-3.9%).
For hospitalists serving only children, the opposite occurred: Pay derived from production fell from 10.7% to 2.8%. While it is not yet clear why compensation, overall, is moving into closer alignment with productivity, rather than performance on quality and safety metrics, one hypothesis is that work relative value units used for calculating productivity are easier to tie to an individual hospitalist than are quality and safety outcomes.
Employee benefits, as previously defined, increased among hospitalists caring for adults only and those caring for adults and children, with a mean increase in both groups of $5,000. The most generous benefits were typically seen at university-based academic medical centers. Amongst adult-only hospitalists, academic groups offer benefits worth $8,000-$9,000 more per year than in nonacademic groups. Lower benefits were common among practices in the Eastern region and in groups with four or fewer full-time hospitalists. The 2016 survey data on CME dollars revealed a median of $3,000-$4,000 per year, with higher amounts provided in nonacademic groups.
Paid time off (PTO) from work is an ongoing topic of interest on venues such as HMX forum, and, in the surveys, PTO remained fairly consistent among groups caring for adults only and those caring for adults and children, with only 30%-40% of groups offering PTO. The number of PTO hours offered vary substantially, however, ranging from a mean of 126 hours up to 216.4 hours annually. Future analysis of PTO will benefit from a deeper understanding of how many hours equate to a shift (the practical definition of a “day off” for most hospitalists).
Finally, the 2016 survey asked about automatic pay increases based strictly on overall experience or length of employment with the group. Roughly one-fifth to one-third of groups provided some sort of salary increase based on experience in 2015. This practice was more common in the Southern region and in nonteaching hospitals. These data raise the complex topic of seniority among hospitalists and how to define it: years since completing training, years with a particular hospital or group, academic rank, leadership roles, other? Further, if seniority is not recognized in pay, how commonly are groups recognizing it in other ways, such as in preferences related to time on certain services, shift type, or vacation requests?
The expanded survey on hospitalist pay, in addition to the biannual comparison of prior data, will likely continue to add value in assessing and exploring the entire package of compensation. Additional topics of interest moving forward might include better understanding of parental leave, sick time, and the comparison between compensation packages for physician hospitalists and those for inpatient Nurse Practitioners and Physician Assistants. Stay tuned for the next report.
Dr. Anoff is associate professor of clinical practice, division of hospital medicine, department of medicine, University of Colorado at Denver, Aurora.
References
1. (2014). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2014.
2. (2016). The State of Hospital Medicine Report. Philadelphia: Society of Hospital Medicine. Retrieved from www.hospitalmedicine.org/Survey2016.