Chronic lymphocytic leukemia cells can be identified at levels as low as 0.0010% with a newly developed and validated single-tube assay, Dr. Andy C. Rawstro of St. James’s Institute of Oncology, Leeds, England, and his colleagues said in a European Research Initiative on CLL (ERIC) project report in Leukemia.

The high-throughput sequencing assay consists of a core panel of six markers – CD19, CD20, CD5, CD43, CD79b and CD81 – with a component specification independent of instrument and reagents. The new assay eliminates the need to distribute the blood sample across multiple tubes, which can impair sensitivity in cases with poor cellularity. The assay can be locally revalidated using normal peripheral blood and can be used to investigate new markers.

The new assay was validated in a multicenter study of 128 samples from 108 patients with CLL or monoclonal B-cell lymphocytosis, studied either at diagnosis or after FCR-based (fludarabine, cyclophosphamide, rituximab) treatment and compared with peripheral blood samples from healthy young women. In a parallel analysis, the assay compared with flow cytometry results at the 0.010% level, the minimal residual disease threshold defined in the 2008 International Workshop on CLL guidelines. The new assay, however, also was able to detect disease at the 0.0010% (one CLL cell in 1 million leukocytes) level.

The ability to detect disease below the levels that can be assessed by flow cytometry may prove to be a valuable resource to improve quantification of minimal residual disease and evaluate treatment response in CLL. Using minimal residual disease as a surrogate measure for treatment effectiveness would avoid the need for prolonged observation times in assessing new therapies, the researchers said (Leukemia 2016;30:929-36).

Dr. Rawstro disclosed receiving honoraria from Celgene, Abbvie, Gilead, Roche, and GSK. He receives royalty payments from BD Biosciences (Intrasure reagent) and study reagents. He is a consultant for Gilead and Biogen Idec.

[email protected]

On Twitter @maryjodales

Chronic lymphocytic leukemia cells can be identified at levels as low as 0.0010% with a newly developed and validated single-tube assay, Dr. Andy C. Rawstro of St. James’s Institute of Oncology, Leeds, England, and his colleagues said in a European Research Initiative on CLL (ERIC) project report in Leukemia.

The high-throughput sequencing assay consists of a core panel of six markers – CD19, CD20, CD5, CD43, CD79b and CD81 – with a component specification independent of instrument and reagents. The new assay eliminates the need to distribute the blood sample across multiple tubes, which can impair sensitivity in cases with poor cellularity. The assay can be locally revalidated using normal peripheral blood and can be used to investigate new markers.

The new assay was validated in a multicenter study of 128 samples from 108 patients with CLL or monoclonal B-cell lymphocytosis, studied either at diagnosis or after FCR-based (fludarabine, cyclophosphamide, rituximab) treatment and compared with peripheral blood samples from healthy young women. In a parallel analysis, the assay compared with flow cytometry results at the 0.010% level, the minimal residual disease threshold defined in the 2008 International Workshop on CLL guidelines. The new assay, however, also was able to detect disease at the 0.0010% (one CLL cell in 1 million leukocytes) level.

The ability to detect disease below the levels that can be assessed by flow cytometry may prove to be a valuable resource to improve quantification of minimal residual disease and evaluate treatment response in CLL. Using minimal residual disease as a surrogate measure for treatment effectiveness would avoid the need for prolonged observation times in assessing new therapies, the researchers said (Leukemia 2016;30:929-36).

Dr. Rawstro disclosed receiving honoraria from Celgene, Abbvie, Gilead, Roche, and GSK. He receives royalty payments from BD Biosciences (Intrasure reagent) and study reagents. He is a consultant for Gilead and Biogen Idec.

[email protected]

On Twitter @maryjodales

Chronic lymphocytic leukemia cells can be identified at levels as low as 0.0010% with a newly developed and validated single-tube assay, Dr. Andy C. Rawstro of St. James’s Institute of Oncology, Leeds, England, and his colleagues said in a European Research Initiative on CLL (ERIC) project report in Leukemia.

The high-throughput sequencing assay consists of a core panel of six markers – CD19, CD20, CD5, CD43, CD79b and CD81 – with a component specification independent of instrument and reagents. The new assay eliminates the need to distribute the blood sample across multiple tubes, which can impair sensitivity in cases with poor cellularity. The assay can be locally revalidated using normal peripheral blood and can be used to investigate new markers.

The new assay was validated in a multicenter study of 128 samples from 108 patients with CLL or monoclonal B-cell lymphocytosis, studied either at diagnosis or after FCR-based (fludarabine, cyclophosphamide, rituximab) treatment and compared with peripheral blood samples from healthy young women. In a parallel analysis, the assay compared with flow cytometry results at the 0.010% level, the minimal residual disease threshold defined in the 2008 International Workshop on CLL guidelines. The new assay, however, also was able to detect disease at the 0.0010% (one CLL cell in 1 million leukocytes) level.

The ability to detect disease below the levels that can be assessed by flow cytometry may prove to be a valuable resource to improve quantification of minimal residual disease and evaluate treatment response in CLL. Using minimal residual disease as a surrogate measure for treatment effectiveness would avoid the need for prolonged observation times in assessing new therapies, the researchers said (Leukemia 2016;30:929-36).

Dr. Rawstro disclosed receiving honoraria from Celgene, Abbvie, Gilead, Roche, and GSK. He receives royalty payments from BD Biosciences (Intrasure reagent) and study reagents. He is a consultant for Gilead and Biogen Idec.

[email protected]

On Twitter @maryjodales

In his April podcast for The Journal of Community and Supportive Oncology, Editor-in-Chief Dr David Henry discusses Original Reports on olanzapine compared with fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting and an analysis of patient-reported outcomes in prostate cancer after treatment with abiraterone acetate. Also among the line-up of Original Reports are studies looking at the diagnostic work-up for the detection of malnutrition in hospitalized cancer patients and at the use of video-conferencing to deliver cancer genetic counseling to high-risk underserved individuals. The Case Reports include an unusual case of non-small-cell lung cancer presenting as spontaneous cardiac tamponade, another of severe eosinophilia associated with cholangiocarcinoma, and a third on acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine. The Community Translations column features approvals of nivolumab approval for metastatic renal-cell carcinoma. Dr Henry also discusses a feature article on new therapies for multiple myeloma that are redefining the condition as a chronic disease.

Listen to the podcast below.

In his April podcast for The Journal of Community and Supportive Oncology, Editor-in-Chief Dr David Henry discusses Original Reports on olanzapine compared with fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting and an analysis of patient-reported outcomes in prostate cancer after treatment with abiraterone acetate. Also among the line-up of Original Reports are studies looking at the diagnostic work-up for the detection of malnutrition in hospitalized cancer patients and at the use of video-conferencing to deliver cancer genetic counseling to high-risk underserved individuals. The Case Reports include an unusual case of non-small-cell lung cancer presenting as spontaneous cardiac tamponade, another of severe eosinophilia associated with cholangiocarcinoma, and a third on acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine. The Community Translations column features approvals of nivolumab approval for metastatic renal-cell carcinoma. Dr Henry also discusses a feature article on new therapies for multiple myeloma that are redefining the condition as a chronic disease.

Listen to the podcast below.

In his April podcast for The Journal of Community and Supportive Oncology, Editor-in-Chief Dr David Henry discusses Original Reports on olanzapine compared with fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting and an analysis of patient-reported outcomes in prostate cancer after treatment with abiraterone acetate. Also among the line-up of Original Reports are studies looking at the diagnostic work-up for the detection of malnutrition in hospitalized cancer patients and at the use of video-conferencing to deliver cancer genetic counseling to high-risk underserved individuals. The Case Reports include an unusual case of non-small-cell lung cancer presenting as spontaneous cardiac tamponade, another of severe eosinophilia associated with cholangiocarcinoma, and a third on acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine. The Community Translations column features approvals of nivolumab approval for metastatic renal-cell carcinoma. Dr Henry also discusses a feature article on new therapies for multiple myeloma that are redefining the condition as a chronic disease.

Listen to the podcast below.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

GLASGOW, SCOTLAND – Treatment with the anti–interleukin-17A monoclonal antibody secukinumab improved a range of patient-reported outcome measures in a phase III trial of patients with ankylosing spondylitis.

Physical function, quality of life, fatigue, and work productivity were all significantly improved from baseline after 16 weeks of treatment with secukinumab (Cosentyx) versus placebo, and the effects were sustained for up to 1 year.

“PROMs [patient-reported outcome measures] are increasingly seen as the most important outcome measures [in trials] because of their importance to patients,” and they are very closely related to long-term retention and patients’ overall quality of life, Dr. Paul Emery said at the British Society for Rheumatology annual conference.

The new findings come from the MEASURE 2 study, a randomized, double-blind trial of 219 patients treated with one of two doses of secukinumab (150 mg or 75 mg) or placebo. Around 60% of the patient population was male, 95% were white, with a mean age around 42-44 years.

The primary endpoint data from the trial, which was the proportion of patients with at least as 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at 16 weeks, were published recently (N Engl J Med. 2015;373:2534-48) with the results of the MEASURE 1 study. These showed that a significantly higher percentage of patients treated with the recommended dose of 150 mg, given as a subcutaneous injection every week for the first 3 weeks, then every 4 weeks from week 4, achieved ASAS 20 versus placebo (61% vs. 28%, P less than .001). Effects were sustained, with 62.5%-73.8% of patients still at ASAS 20 at 1 year depending on the type of data analysis performed, and 75% of those who switched from placebo at 16 weeks. The highest response rates were seen in patients who had not received prior anti-TNF therapy (82% vs. 60% for prior therapy at 1 year).

Changes in patients’ general and disease-specific quality of life from baseline to week 16 were predefined secondary endpoints assessed in the MEASURE 2 trial and were determined by the Short-Form (SF) 36 Physical Component Score (PCS) and the AS Quality of Life (ASQoL) questionnaire. Other exploratory endpoints included assessment of these measures at 1 year and the effect of treatment on the SF-36 Mental Component Score (MCS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue questionnaire, and the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire.

“One of the things about secukinumab is that you do get very fast responses in the things that matter,” said Dr. Emery of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds.

Improvement in SF-36 PCS showed improvement as early as week 4, with a mean increase of 6 points from baseline with secukinumab 150 mg versus only 1.9 points for placebo at week 16, and a sustained improvement of 8 points by 1 year. The minimal clinically important difference (MCID) for change in SF-36 is 2.5 points or more. There was not such a clear-cut difference for the SF-36 MCS, but there was a clinically significant improvement of about 4 points at 16 weeks and 6.5 by 1 year.

There was a significant improvement in quality of life versus placebo measured using the ASQoL instrument, with a mean reduction of 4 points for the recommended dose of secukinumab at 16 weeks versus a 1.4 reduction for placebo, and a 5.23 reduction for secukinumab at 1 year. Here the MCID is a change of 1.8 points, Dr. Emery reported.

The MCID for changes in the FACIT-Fatigue score is 4 points or more and this was passed by secukinumab 150 mg at both 16 weeks, with a change of 8 points versus 3.3 points for placebo, and at 1 year, with an increase of 11.5 points for secukinumab.

Work productivity impairment was also improved with active treatment, with mean changes in the WPAI-GH from baseline to week 16 of –16.36 versus –10.22 for placebo, and a sustained reduction of 21.33 at 1 year. Higher scores on this outcome measure mean that work productivity is more severely affected.

Secukinumab was approved for use in ankylosing spondylitis by the European Medicines Agency in October 2015 and more recently by the Food and Drug Administration in January this year. Its availability could be a potential “game changer” for these patients, Dr. Emery suggested, because its mode of action is different from other available therapies, notably the tumor necrosis factor inhibitors. It could become the treatment of choice for AS patients, partially those with enthesitis and psoriasis, at least before drugs that target interleukin (IL)-23 become available that may be better for addressing the spinal component of the disease, he noted during the Q&A that followed his presentation.

Data on radiographic progression will be presented separately, Dr. Emery noted during discussion. He added that secukinumab “certainly works” to reduce radiographic progression, but whether or not it is better than anti-TNF therapy remains to be seen. Because of the mechanism of action on IL-17A, secukinumab could potentially offer an advantage, he said.

“I think it is a game changer because we’ve had such restricted access to therapy previously,” Dr. Emery said. Now having drugs with two different modes of action is a bonus. Deciding which to use first, and in which patients, is the next issue to address.

Novartis supported the study. Dr. Emery has been a paid consultant to AbbVie, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, UCB, Lilly, Samsung, and Sandoz.

In the first two installments of my own list of attributes that are important underpinnings of successful hospitalist groups, I covered group culture and decision making, recruiting, the importance of a written policy and procedure manual and performance dashboard, and roles for advanced practice clinicians. I’ll continue numbering from last month and complete the list in this column.

7. Clear Reporting Relationships

Most hospitalists are employed by one entity, usually a hospital subcorporation or staffing company, yet in many respects they report to someone else, such as a hospital CMO. For many, this can feel like serving two masters.

As an example, a hospitalist is employed by St. Excellence Medical Group (SEMG), a subsidiary of St. Excellence Hospital. Yet the hospital CMO is the key person establishing hospitalist performance targets, mediating disagreements between hospitalists and cardiologists, etc. So the hospitalists and CMO might jointly make plans for changes in the hospitalist practice that have staffing or budgetary implications only to find that the SEMG president resists spending more on the hospitalist program. For some hospitalist groups, this problem of being stuck between two masters can be a real barrier to getting things done.

Because the employed physician group nearly always directs most of its attention to outpatient care, the hospitalists are sometimes an afterthought, sort of a like a neglected stepchild. And worse, I’ve worked with more than one organization in which the CMO and physician president of the employed physician group are engaged in a power struggle, with the hospitalist group (and other physician specialties) caught in the middle and suffering as a result.

I think the best way out of this dilemma is for the employed physician group to function as a management services organization, providing human resources (payroll, etc.) and revenue cycle functions to the hospitalist groups. But for nearly all other issues, such as policies and procedures, staffing, strategic planning, hiring and firing, etc., the lead hospitalist should report to the CMO.

8. Well-Organized Group Meetings

My experience is that nearly every hospitalist group has periodic meetings to discuss and make decisions on operational and clinical issues. But the effectiveness of the meetings varies a lot. In some cases, they’re little more than disorganized gripe sessions.

I think most groups should have monthly meetings scheduled for about an hour or a little longer. Attendance at most meetings should be the expectation; that means even those not working clinically that day should be expected to attend unless away on vacation or some other meaningful conflict. Simply not being on clinical service that day should not be a reason to miss the meeting. Attendance by phone periodically is usually fine, especially for those who would otherwise have a long drive to attend in person or have child care duties, etc.

An agenda should be circulated in advance of the meeting; minutes, afterward. The best minutes highlight any “to-do” items, including person responsible and target completion date. Tasks occurring over longer than a month should be tracked in the minutes of every meeting until resolved. All past meeting minutes should be readily accessible via a network computer drive for review by any member of the group at any time.

Although some of every meeting will typically need to be devoted to one-way communication from the group leader or others, ideally in every meeting meaningful time should be devoted to joint problem-solving by all in attendance to ensure all are engaged in the meetings and find them useful. Some one-way communication (e.g., regular reports of performance data) typically can be distributed via email and other means rather than devoting meeting time to review it.

9. Effective Compensation

The amount of compensation should be competitive with your market, but because compensation is typically seen as an entitlement, unusually high compensation amounts usually have little impact on performance. But the method of compensation can matter, that is, the portion of total dollars that are fixed, tied to production, or tied to performance.

I think it’s best if the compensation method is generally similar to the way Medicare and other payors reimburse physician services. As payors tie increasing portions of compensation to performance and bundled payments, it makes sense for these changes to be mirrored in hospitalist compensation formulas to the extent that is practical. As I’ve written in February 2014 and many other times, I think there will always be a role for a portion of compensation tied to individual productivity.

According to SHM’s 2014 State of Hospital Medicine report, 64% of hospitalist groups have some component of compensation tied to citizenship activities such as committee participation, grand rounds presentations, community talks, publications, etc. I described a citizenship bonus program in detail in my November 2011 column. And while I was once an advocate of it, I’m now ambivalent. My anecdotal experience with the group I’m part of and many others I’ve worked with makes me suspect that a bonus for good citizenship might just squash intrinsic motivation as described in Daniel Pink’s book Drive.

If you do tie some portion of compensation to citizenship, I strongly encourage not connecting it to basic expectations like meeting attendance or turning in billing data on time. These are standard parts of the job, and citizenship pay should be reserved for going beyond the basics.

10. Good Social Connections

The way things look to me, doctors across all specialties have historically enjoyed robust and rewarding social connections with one another. But with each passing year, the nature of the work, financial pressures, and even clinical vocabulary become more and more different; that is, our Venn diagrams overlap less and less.

I think doctors in different specialties are becoming less connected, and disagreements or new stresses can more easily divide us.

Although all hospitals and medical groups are working hard to implement operational and technical adjustments to keep up with changing clinical practice and reimbursement models, I see very few deliberately focused on maintaining or strengthening the social connections and feeling of occupational solidarity and shared mission across doctors and other providers (see my June 2010 column). Those that do so—to my way of thinking—will be uniquely positioned to weather the storm of rapid change much more effectively. TH

In the first two installments of my own list of attributes that are important underpinnings of successful hospitalist groups, I covered group culture and decision making, recruiting, the importance of a written policy and procedure manual and performance dashboard, and roles for advanced practice clinicians. I’ll continue numbering from last month and complete the list in this column.

7. Clear Reporting Relationships

Most hospitalists are employed by one entity, usually a hospital subcorporation or staffing company, yet in many respects they report to someone else, such as a hospital CMO. For many, this can feel like serving two masters.

As an example, a hospitalist is employed by St. Excellence Medical Group (SEMG), a subsidiary of St. Excellence Hospital. Yet the hospital CMO is the key person establishing hospitalist performance targets, mediating disagreements between hospitalists and cardiologists, etc. So the hospitalists and CMO might jointly make plans for changes in the hospitalist practice that have staffing or budgetary implications only to find that the SEMG president resists spending more on the hospitalist program. For some hospitalist groups, this problem of being stuck between two masters can be a real barrier to getting things done.

Because the employed physician group nearly always directs most of its attention to outpatient care, the hospitalists are sometimes an afterthought, sort of a like a neglected stepchild. And worse, I’ve worked with more than one organization in which the CMO and physician president of the employed physician group are engaged in a power struggle, with the hospitalist group (and other physician specialties) caught in the middle and suffering as a result.

I think the best way out of this dilemma is for the employed physician group to function as a management services organization, providing human resources (payroll, etc.) and revenue cycle functions to the hospitalist groups. But for nearly all other issues, such as policies and procedures, staffing, strategic planning, hiring and firing, etc., the lead hospitalist should report to the CMO.

8. Well-Organized Group Meetings

My experience is that nearly every hospitalist group has periodic meetings to discuss and make decisions on operational and clinical issues. But the effectiveness of the meetings varies a lot. In some cases, they’re little more than disorganized gripe sessions.

I think most groups should have monthly meetings scheduled for about an hour or a little longer. Attendance at most meetings should be the expectation; that means even those not working clinically that day should be expected to attend unless away on vacation or some other meaningful conflict. Simply not being on clinical service that day should not be a reason to miss the meeting. Attendance by phone periodically is usually fine, especially for those who would otherwise have a long drive to attend in person or have child care duties, etc.

An agenda should be circulated in advance of the meeting; minutes, afterward. The best minutes highlight any “to-do” items, including person responsible and target completion date. Tasks occurring over longer than a month should be tracked in the minutes of every meeting until resolved. All past meeting minutes should be readily accessible via a network computer drive for review by any member of the group at any time.

Although some of every meeting will typically need to be devoted to one-way communication from the group leader or others, ideally in every meeting meaningful time should be devoted to joint problem-solving by all in attendance to ensure all are engaged in the meetings and find them useful. Some one-way communication (e.g., regular reports of performance data) typically can be distributed via email and other means rather than devoting meeting time to review it.

9. Effective Compensation

The amount of compensation should be competitive with your market, but because compensation is typically seen as an entitlement, unusually high compensation amounts usually have little impact on performance. But the method of compensation can matter, that is, the portion of total dollars that are fixed, tied to production, or tied to performance.

I think it’s best if the compensation method is generally similar to the way Medicare and other payors reimburse physician services. As payors tie increasing portions of compensation to performance and bundled payments, it makes sense for these changes to be mirrored in hospitalist compensation formulas to the extent that is practical. As I’ve written in February 2014 and many other times, I think there will always be a role for a portion of compensation tied to individual productivity.

According to SHM’s 2014 State of Hospital Medicine report, 64% of hospitalist groups have some component of compensation tied to citizenship activities such as committee participation, grand rounds presentations, community talks, publications, etc. I described a citizenship bonus program in detail in my November 2011 column. And while I was once an advocate of it, I’m now ambivalent. My anecdotal experience with the group I’m part of and many others I’ve worked with makes me suspect that a bonus for good citizenship might just squash intrinsic motivation as described in Daniel Pink’s book Drive.

If you do tie some portion of compensation to citizenship, I strongly encourage not connecting it to basic expectations like meeting attendance or turning in billing data on time. These are standard parts of the job, and citizenship pay should be reserved for going beyond the basics.

10. Good Social Connections

The way things look to me, doctors across all specialties have historically enjoyed robust and rewarding social connections with one another. But with each passing year, the nature of the work, financial pressures, and even clinical vocabulary become more and more different; that is, our Venn diagrams overlap less and less.

I think doctors in different specialties are becoming less connected, and disagreements or new stresses can more easily divide us.

Although all hospitals and medical groups are working hard to implement operational and technical adjustments to keep up with changing clinical practice and reimbursement models, I see very few deliberately focused on maintaining or strengthening the social connections and feeling of occupational solidarity and shared mission across doctors and other providers (see my June 2010 column). Those that do so—to my way of thinking—will be uniquely positioned to weather the storm of rapid change much more effectively. TH

In the first two installments of my own list of attributes that are important underpinnings of successful hospitalist groups, I covered group culture and decision making, recruiting, the importance of a written policy and procedure manual and performance dashboard, and roles for advanced practice clinicians. I’ll continue numbering from last month and complete the list in this column.

7. Clear Reporting Relationships

Most hospitalists are employed by one entity, usually a hospital subcorporation or staffing company, yet in many respects they report to someone else, such as a hospital CMO. For many, this can feel like serving two masters.

As an example, a hospitalist is employed by St. Excellence Medical Group (SEMG), a subsidiary of St. Excellence Hospital. Yet the hospital CMO is the key person establishing hospitalist performance targets, mediating disagreements between hospitalists and cardiologists, etc. So the hospitalists and CMO might jointly make plans for changes in the hospitalist practice that have staffing or budgetary implications only to find that the SEMG president resists spending more on the hospitalist program. For some hospitalist groups, this problem of being stuck between two masters can be a real barrier to getting things done.

Because the employed physician group nearly always directs most of its attention to outpatient care, the hospitalists are sometimes an afterthought, sort of a like a neglected stepchild. And worse, I’ve worked with more than one organization in which the CMO and physician president of the employed physician group are engaged in a power struggle, with the hospitalist group (and other physician specialties) caught in the middle and suffering as a result.

I think the best way out of this dilemma is for the employed physician group to function as a management services organization, providing human resources (payroll, etc.) and revenue cycle functions to the hospitalist groups. But for nearly all other issues, such as policies and procedures, staffing, strategic planning, hiring and firing, etc., the lead hospitalist should report to the CMO.

8. Well-Organized Group Meetings

My experience is that nearly every hospitalist group has periodic meetings to discuss and make decisions on operational and clinical issues. But the effectiveness of the meetings varies a lot. In some cases, they’re little more than disorganized gripe sessions.

I think most groups should have monthly meetings scheduled for about an hour or a little longer. Attendance at most meetings should be the expectation; that means even those not working clinically that day should be expected to attend unless away on vacation or some other meaningful conflict. Simply not being on clinical service that day should not be a reason to miss the meeting. Attendance by phone periodically is usually fine, especially for those who would otherwise have a long drive to attend in person or have child care duties, etc.

An agenda should be circulated in advance of the meeting; minutes, afterward. The best minutes highlight any “to-do” items, including person responsible and target completion date. Tasks occurring over longer than a month should be tracked in the minutes of every meeting until resolved. All past meeting minutes should be readily accessible via a network computer drive for review by any member of the group at any time.

Although some of every meeting will typically need to be devoted to one-way communication from the group leader or others, ideally in every meeting meaningful time should be devoted to joint problem-solving by all in attendance to ensure all are engaged in the meetings and find them useful. Some one-way communication (e.g., regular reports of performance data) typically can be distributed via email and other means rather than devoting meeting time to review it.

9. Effective Compensation

The amount of compensation should be competitive with your market, but because compensation is typically seen as an entitlement, unusually high compensation amounts usually have little impact on performance. But the method of compensation can matter, that is, the portion of total dollars that are fixed, tied to production, or tied to performance.

I think it’s best if the compensation method is generally similar to the way Medicare and other payors reimburse physician services. As payors tie increasing portions of compensation to performance and bundled payments, it makes sense for these changes to be mirrored in hospitalist compensation formulas to the extent that is practical. As I’ve written in February 2014 and many other times, I think there will always be a role for a portion of compensation tied to individual productivity.

According to SHM’s 2014 State of Hospital Medicine report, 64% of hospitalist groups have some component of compensation tied to citizenship activities such as committee participation, grand rounds presentations, community talks, publications, etc. I described a citizenship bonus program in detail in my November 2011 column. And while I was once an advocate of it, I’m now ambivalent. My anecdotal experience with the group I’m part of and many others I’ve worked with makes me suspect that a bonus for good citizenship might just squash intrinsic motivation as described in Daniel Pink’s book Drive.

If you do tie some portion of compensation to citizenship, I strongly encourage not connecting it to basic expectations like meeting attendance or turning in billing data on time. These are standard parts of the job, and citizenship pay should be reserved for going beyond the basics.

10. Good Social Connections

The way things look to me, doctors across all specialties have historically enjoyed robust and rewarding social connections with one another. But with each passing year, the nature of the work, financial pressures, and even clinical vocabulary become more and more different; that is, our Venn diagrams overlap less and less.

I think doctors in different specialties are becoming less connected, and disagreements or new stresses can more easily divide us.

Although all hospitals and medical groups are working hard to implement operational and technical adjustments to keep up with changing clinical practice and reimbursement models, I see very few deliberately focused on maintaining or strengthening the social connections and feeling of occupational solidarity and shared mission across doctors and other providers (see my June 2010 column). Those that do so—to my way of thinking—will be uniquely positioned to weather the storm of rapid change much more effectively. TH

NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.

As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent

cardiovascular event, as compared to patients not taking clopidogrel on admission."

The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.

Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.

Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant  difference in the frequency of bleeding events.

Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior

cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."

"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."

NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.

As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent

cardiovascular event, as compared to patients not taking clopidogrel on admission."

The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.

Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.

Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant  difference in the frequency of bleeding events.

Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior

cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."

"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."

NEW YORK (Reuters Health) - Among medically treated patients with acute coronary syndrome (ACS), prior clopidogrel therapy appears to be associated with more cardiovascular events, researchers have found.

As Dr. Chee Tang Chin told Reuters Health by email, "We found that among patients who were admitted for an acute coronary syndrome and did not undergo coronary revascularization, those patients who were already taking clopidogrel were at a higher risk for a subsequent

cardiovascular event, as compared to patients not taking clopidogrel on admission."

The study, a prespecified subanalysis of the TRILOGY ACS trial, was published online March 30 in Heart.

Of almost 9,000 patients, 73% first received clopidogrel in-hospital within 72 hours of presentation and daily until randomization to clopidogrel versus prasugrel (plus aspirin). The remaining 27% were taking clopidogrel prior to admission and continued daily clopidogrel therapy until the date of randomization.

Over 30 months, those with prior clopidogrel use had a significantly higher frequency of cardiovascular death, MI and stroke (20.8% vs. 18.3%, p=0.002). There was no significant  difference in the frequency of bleeding events.

Dr. Chin pointed out that in the prior users, "This excess risk was largely accounted for by the higher burden of high-risk co-morbidities among this group, such as diabetes and prior

cardiovascular disease. However, consistent with the overall TRILOGY-ACS results, the use of a more potent antiplatelet agent such as prasugrel did not modify this risk."

"These results," Dr. Chin concluded, "are important as they imply that among ACS patients treated only medically, strategies beyond platelet inhibition need to be considered for further optimizing outcomes."

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”

Red blood cells

Researchers say they have used a rational design approach to create a safer variant of the drug erythropoietin (EPO).

This “targeted EPO” effectively stimulated red blood cell production in mice and had a minimal impact on platelets.

The team believes this approach could allow for the use of higher restorative doses of EPO without platelet-mediated side effects, and it might improve drug pharmacokinetics.

Devin Burrill, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts, and his colleagues described the approach in PNAS.

The researchers noted that EPO has been widely used to treat anemia, but the drug also poses a risk of thrombotic complications. To combat this problem, the team set out to design a more effective, multi-part drug molecule.

“Compared to currently available EPO drugs, our molecule is engineered to prevent EPO from binding to and activating cells that promote side effects such as blood clotting or tumor growth,” said Jeffrey Way, PhD, also of the Wyss Institute.

“This cell-targeted EPO approach demonstrates a new theoretical basis for the rational design of engineered protein fusion drugs.”

To create their drug, the researchers first mutated EPO to reduce its ability to bind to EPO receptors.

Then, using a chain of amino acids as a flexible linker, they attached mutated EPO to an antibody fragment that specifically binds the human red blood cell marker glycophorin A (huGYPA). This antibody fragment binds to red blood cell precursors while avoiding other types of blood cells.

When the team’s fusion protein molecules were delivered to huGYPA transgenic mice, the antibody fragments piloted toward and bound to the membranes of red blood cell precursors, towing along EPO molecules on the other end of their linkers.

In such close proximity to the surface of the cells, a high concentration of tethered EPO bounced around until it ultimately toggled into place on the cells’ receptors. In this way, red blood cell production was increased with only minimal effects on platelets.

“Our rational design strategy is unique compared to current industry approaches,” Dr Burrill said. “Our goal is to use our method to advance predictive drug design and minimize the time between drug concept and commercialization.”

“The principles of synthetic biology influenced our efforts,” added James Collins, PhD, of the Wyss Institute.

“In drug development, the focus is typically on increasing the strength of interaction with a drug target, but, here, we found that weakening an interaction was useful. This illustrates how we need to adopt alternative, non-traditional approaches if we want to build complex, multi-part therapeutics.”

The researchers said this specific, cell-targeted approach could be applied quite broadly. In addition to “targeted EPO,” the team has developed “targeted interferon-alfa.”

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.

ALL patient

Photo by Bill Branson

High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.

Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.

In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.

The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.

Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.

“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.

“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”

Treatment

Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.

Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.

So the treatment groups were as follows:

• Prednisone and escalating MTX (n=926)
• Prednisone and high-dose MTX (n=926)
• Dexamethasone and escalating MTX (n=535)
• Dexamethasone and high-dose MTX (n=527).

MTX results

At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).

The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).

There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).

There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).

But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.

Corticosteroid results

Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.

However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.

Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.

The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).

For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).

Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).

However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).

Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).

There were no other significant differences in adverse events between the 2 corticosteroid regimens.

ALL patient

Photo by Bill Branson

High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.

Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.

In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.

The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.

Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.

“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.

“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”

Treatment

Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.

Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.

So the treatment groups were as follows:

• Prednisone and escalating MTX (n=926)
• Prednisone and high-dose MTX (n=926)
• Dexamethasone and escalating MTX (n=535)
• Dexamethasone and high-dose MTX (n=527).

MTX results

At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).

The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).

There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).

There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).

But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.

Corticosteroid results

Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.

However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.

Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.

The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).

For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).

Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).

However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).

Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).

There were no other significant differences in adverse events between the 2 corticosteroid regimens.

ALL patient

Photo by Bill Branson

High-dose methotrexate (MTX) is more effective than escalating doses of MTX for young patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a study published in the Journal of Clinical Oncology.

Patients who received high-dose MTX during interim maintenance 1 had significantly better event-free survival (EFS) than those who received escalating MTX.

In addition, the study showed that substituting dexamethasone for prednisone during induction was beneficial for younger—but not older—patients.

The high-dose MTX protocol outlined in this study, and the use of dexamethasone in younger patients, has become the standard practice for the treatment of high-risk ALL patients in North America.

Prior to the release of the initial study results, which were first presented last year at the ASCO Annual Meeting, the standard of care for high-risk ALL patients in North America was escalating MTX.

“One of the improvements in outcome for ALL overall has been using methotrexate in a more intense fashion, by giving higher doses,” said study investigator William L. Carroll, MD, of NYU Langone Medical Center in New York, New York.

“We designed this study to compare high-dose and escalating methotrexate to determine the best way to use this drug to increase the survival of high-risk ALL patients.”

Treatment

Between January 2004 and January 2011, Dr Carroll and his colleagues enrolled 3154 patients, ages 1 to 30, with newly diagnosed, high-risk B-ALL. After exclusions, 2914 patients were randomized to treatment.

Using a 2 × 2 factorial design, the patients were randomized to receive dexamethasone for 14 days or prednisone for 28 days during induction and high-dose MTX or Capizzi escalating-dose MTX plus pegaspargase during interim maintenance 1.

So the treatment groups were as follows:

• Prednisone and escalating MTX (n=926)
• Prednisone and high-dose MTX (n=926)
• Dexamethasone and escalating MTX (n=535)
• Dexamethasone and high-dose MTX (n=527).

MTX results

At the planned interim analysis, the 5-year EFS was 82% among patients who received high-dose MTX and 75.4% among those who received escalating MTX (P=0.006).

The final data showed 5-year EFS rates of 79.6% and 75.2%, respectively (P=0.008) and 5-year overall survival rates of 88.9% and 86.1%, respectively (P=0.025).

There was a higher rate of febrile neutropenia during interim maintenance 1 among patients who received escalating MTX than among those who received high-dose MTX—8.3% and 5.1%, respectively (P=0.003).

There were 5 cases of ischemic cerebrovascular toxicity among patients who received high-dose MTX and none among the patients who received escalating MTX (P=0.03).

But there were no other significant differences in adverse events between the high-dose and escalating-dose MTX groups.

Corticosteroid results

Patients age 10 and older saw no benefit from dexamethasone, and, in fact, were at much higher risk of developing osteonecrosis. Because of this risk, the corticosteroid induction arm of this study was closed early, in 2008.

However, the investigators found that patients younger than age 10 did benefit from dexamethasone exposure.

Specifically, patients under 10 who received dexamethasone and high-dose MTX had significantly better EFS than patients who received the other 3 treatment regimens.

The 5-year EFS rate was 91.2% in the dexamethasone and high-dose MTX arm, 83.2% in the dexamethasone and escalating MTX arm, 80.8% in the prednisone and high-dose MTX arm, and 82.1% in the prednisone and escalating MTX arm (P=0.015).

For patients of all ages, there was a higher rate of febrile neutropenia during induction among patients who received dexamethasone than among those who received prednisone—18.2% and 11.0%, respectively (P<0.001).

Patients who received dexamethasone also had a higher rate of infections/infestations—29.4% and 20.3%, respectively (P<0.001).

However, there was no significant difference in induction death rate—1.9% and 1.8%, respectively (P=0.87). The same was true when the investigators looked only at patients younger than 10 (P=0.71) or at patients 10 and older (P=0.69).

Among patients ages 10 and older who participated in the induction corticosteroid randomization before it was closed, the 5-year cumulative incidence of osteonecrosis was 24.3% for patients who received dexamethasone and 15.9% for those who received prednisone (P=0.001).

There were no other significant differences in adverse events between the 2 corticosteroid regimens.