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PAP sensor may cut real-world heart failure hospitalization
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Real-world evidence about the PAP sensor is particularly important, because the FDA approved the device amid considerable controversy over the CHAMPION trial and its sponsor. Employees of the sponsor were considered to have contaminated the initial data, and the FDA initially rejected the device. Substantial uncertainty still persists concerning the sensor’s effectiveness in reducing HF hospitalizations.
In addition, the percentage of HF patients who have received the device is extremely small, given that the study and the highly selected patient sample make both causal inferences and generalizability of the findings difficult.
The net effect of these important limitations is that the study by Desai et al. lacks the strength to change prior assumptions about the PAP sensor’s benefits in any direction. Unfortunately, this study doesn’t have the evidentiary robustness to inform clinical decisions.
Harlan M. Krumholz, MD, and Sanket S. Dhruva, MD, are both in the Robert Wood Johnson Foundation Clinical Scholars Program and at the Yale School of Medicine and Yale School of Public Health in New Haven, Conn. Dr. Krumholz reported ties to Johnson & Johnson and Medtronic; Dr. Dhruva reported having no relevant financial disclosures. They made these remarks in an editorial accompanying the study (J Am Coll Cardiol. 2017 Mar 19. doi:10.1016/j.jacc.2017.03.019).
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant 45% reduction in HF hospitalization and its attendant substantial costs in a real-world patient population, Akshay S. Desai, MD, said at the annual meeting of the American College of Cardiology.
The PAP sensor is used to monitor pulmonary artery filling pressure, which rises in many HF patients during the weeks preceding an HF exacerbation. This early detection of progressing congestion allows clinicians to intervene earlier and head off hospitalization for the exacerbation.
Their intention was to determine whether the positive results of the CHAMPION clinical trial, which prompted FDA approval of the device as a means to reduce HF-associated hospitalizations, could be replicated in a real-world population, said Dr. Desai of Brigham and Women’s Hospital, Boston.
The results of their study were presented March 19 at the annual meeting of the American College of Cardiology and simultaneously published online in the Journal of the American College of Cardiology (2017 Mar 19. doi: 10.1016/j.jacc.2017.03.009).
The mean age of the study cohort was 71 years, and 40% of the participants were at least 75 years of age. Women composed 40% of the cohort. There was a high burden of comorbid illness, including diabetes, hypertension, and chronic obstructive pulmonary disease. This represents a broader sample than was enrolled in the CHAMPION trial, he noted.
There were 1,020 HF hospitalizations before implantation and 381 afterward. A total of 59% of patients had at least one HF hospitalization before the PAP implantation, compared with 22% afterward. The median number of HF hospitalizations was 0.92 per patient before implantation and 0.37 per patient afterward.
Further analysis showed that the cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55). This finding remained robust across several subgroups of patients and in several sensitivity analyses.
These reductions were associated with a corresponding decline in costs related to HF care, which dropped by $7,433 per patient.
In addition to HF-related hospitalizations, all-cause hospitalizations also declined by roughly 30% after implantation of a PAP sensor (HR, 0.69).
These findings suggest that the reduction in hospitalizations, along with attendant reductions in the costs of care, may be achievable in real-world practice. The 45% drop in HF hospitalizations in this study “compares favorably with the 28% reduction seen with PAP-guided therapy over the same time period in the randomized CHAMPION study that supported the initial FDA approval,” Dr. Desai said.
Moreover, a subgroup of 480 patients had data for 12 months preceding and 12 months following implantation. Analysis of those data showed that the benefits of PAP monitoring to guide HF care “were consistent over longer-term follow-up, with a 34% reduction in HF hospitalizations sustained at 12 months,” he added.
The study had several limitations. It excluded Medicare Part D data, so medication changes related to implantation could not be examined and may have exerted substantial influence on study outcomes.
It also didn’t include the actual PAP-sensor data, “which makes it challenging to confirm that physicians intervened to treat elevated PAPs” and that that intervention is the reason for the study outcomes.
“We were unable to definitively ascertain whether reduced HF hospitalizations are related to undertreatment in the preimplant period or improved treatment in the postimplant period,” Dr. Desai said.
The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
FROM ACC 17
Key clinical point: Implantation of a pulmonary artery pressure sensor to guide care in chronic heart failure was associated with a significant reduction in HF hospitalizations and associated substantial costs.
Major finding: The cumulative rate of HF hospitalization was 45% lower during the 6 months after implantation than during the 6 months preceding it (hazard ratio, 0.55).
Data source: A retrospective observational cohort study comparing HF hospitalizations during the 6 months before and the 6 months after PAP sensor implantation in 1,114 Medicare patients.
Disclosures: The study was sponsored by Abbott, maker of the CardioMEMS PAP sensor. Dr. Desai and his associates reported ties to Abbott and St. Jude Medical.
Pilot Program Will Integrate Trauma-Informed Care for Native Children
Ten IHS sites will take part in a new year-long pilot project to integrate trauma-informed care for children through a partnership between IHS, Johns Hopkins Center for Mental Health Services in Pediatric Primary Care, and Johns Hopkins Center for American Indian Health. “The quality of care for our youngest patients is important…” said Rear Admiral Chris Buchanan, acting director of the IHS. The collaboration is designed to reduce the effects of childhood traumatic stress due to poverty, physical or sexual abuse, community and school violence, and neglect.
The IHS and tribal pilot sites will receive virtual technical assistance through webinars, virtual learning communities, technical assistance calls, and metrics collection and analysis. IHS is working with the Pediatric Integrated Care Collaborative (PICC), part of the Johns Hopkins Center for Mental Health Services in Pediatric Primary Care. PICC works with national faculty, pediatric primary care providers, mental health professionals, and families to integrate behavioral and physical health services in Native communities.
The project uses a “learning collaborative” method in which newly learned processes are implemented and then evaluated to find out what works well and what does not and what changes might be needed. Staff are encouraged to test practical, sustainable approaches of integrating trauma/chronic stress prevention, detection, and early intervention into primary care for young children. Identified approaches may include providing primary and secondary prevention, screening for trauma-related problems, or treating trauma-related problems, the IHS says.
“We are honored to be able to work with a group of tribal communities and the IHS on trauma-informed integrated care,” said Lawrence Wissow, MD, professor, Division of Child and Adolescent Psychiatry at Johns Hopkins School of Medicine. “[W]e know that the larger integrated care world will learn from solutions that incorporate Native American traditions of healing and collaboration.”
Ten IHS sites will take part in a new year-long pilot project to integrate trauma-informed care for children through a partnership between IHS, Johns Hopkins Center for Mental Health Services in Pediatric Primary Care, and Johns Hopkins Center for American Indian Health. “The quality of care for our youngest patients is important…” said Rear Admiral Chris Buchanan, acting director of the IHS. The collaboration is designed to reduce the effects of childhood traumatic stress due to poverty, physical or sexual abuse, community and school violence, and neglect.
The IHS and tribal pilot sites will receive virtual technical assistance through webinars, virtual learning communities, technical assistance calls, and metrics collection and analysis. IHS is working with the Pediatric Integrated Care Collaborative (PICC), part of the Johns Hopkins Center for Mental Health Services in Pediatric Primary Care. PICC works with national faculty, pediatric primary care providers, mental health professionals, and families to integrate behavioral and physical health services in Native communities.
The project uses a “learning collaborative” method in which newly learned processes are implemented and then evaluated to find out what works well and what does not and what changes might be needed. Staff are encouraged to test practical, sustainable approaches of integrating trauma/chronic stress prevention, detection, and early intervention into primary care for young children. Identified approaches may include providing primary and secondary prevention, screening for trauma-related problems, or treating trauma-related problems, the IHS says.
“We are honored to be able to work with a group of tribal communities and the IHS on trauma-informed integrated care,” said Lawrence Wissow, MD, professor, Division of Child and Adolescent Psychiatry at Johns Hopkins School of Medicine. “[W]e know that the larger integrated care world will learn from solutions that incorporate Native American traditions of healing and collaboration.”
Ten IHS sites will take part in a new year-long pilot project to integrate trauma-informed care for children through a partnership between IHS, Johns Hopkins Center for Mental Health Services in Pediatric Primary Care, and Johns Hopkins Center for American Indian Health. “The quality of care for our youngest patients is important…” said Rear Admiral Chris Buchanan, acting director of the IHS. The collaboration is designed to reduce the effects of childhood traumatic stress due to poverty, physical or sexual abuse, community and school violence, and neglect.
The IHS and tribal pilot sites will receive virtual technical assistance through webinars, virtual learning communities, technical assistance calls, and metrics collection and analysis. IHS is working with the Pediatric Integrated Care Collaborative (PICC), part of the Johns Hopkins Center for Mental Health Services in Pediatric Primary Care. PICC works with national faculty, pediatric primary care providers, mental health professionals, and families to integrate behavioral and physical health services in Native communities.
The project uses a “learning collaborative” method in which newly learned processes are implemented and then evaluated to find out what works well and what does not and what changes might be needed. Staff are encouraged to test practical, sustainable approaches of integrating trauma/chronic stress prevention, detection, and early intervention into primary care for young children. Identified approaches may include providing primary and secondary prevention, screening for trauma-related problems, or treating trauma-related problems, the IHS says.
“We are honored to be able to work with a group of tribal communities and the IHS on trauma-informed integrated care,” said Lawrence Wissow, MD, professor, Division of Child and Adolescent Psychiatry at Johns Hopkins School of Medicine. “[W]e know that the larger integrated care world will learn from solutions that incorporate Native American traditions of healing and collaboration.”
NCCN myelofibrosis guideline: Patient voice is key
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
EXPERT ANALYSIS AT THE NCCN ANNUAL CONFERENCE
NCI to Study African-American Cancer Survivors
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Studies have shown that African Americans have higher incidences of cancer than that of other racial/ethnic groups. They also are more likely to be diagnosed later and to die of the cancer. Compared with whites, African Americans have poorer survival rates for the 4 most common types of cancer (lung, breast, prostate, and colorectal). The ready-to-launch Detroit Research on Cancer Survivors study, funded by the National Cancer Institute (NCI), is “uniquely poised” to find out why, said Douglas Lowy, MD, acting director of NCI.
The largest such study to date will include 5,560 African American cancer survivors and 2,780 family members and will look at cancer progression, recurrence, mortality as well as quality of life for survivors and their families. The researchers will investigate the “myriad factors that may affect cancer survival,” including type of treatment, coexisting disease, genetics, social structure, support, neighborhood context, poverty, stress, racial discrimination, and literacy.
The participants are drawn from 3 counties around Detroit where about 21,000 people are diagnosed with cancer every year. The study also uses data from the Detroit area population-based cancer registry, part of NCI’s Surveillance, Epidemiology and End Results (SEER) Program. Joanne Elena, PhD, MPH, scientific program director for the grant funding the study, calls it a “great example of an efficient use of an existing structure to rapidly recruit cancer survivors into research studies.”
The grant is for $9 million over 5 years. “Investigating the complex factors that lead to disparities in cancer among underserved populations should lead to a greater understanding of the social and biologic causes of such differences,” said Robert Croyle, PhD, director of NCI’s Division of Cancer Control and Population Sciences. “And our hope is that this knowledge will lead to better outcomes.”
Reusing Syringes: Not Safe, Not Cost-Effective
In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months. This was not the hospital’s practice.
Because she had been putting patients at risk for bloodborne pathogens, the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.
Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.
Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.
In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months. This was not the hospital’s practice.
Because she had been putting patients at risk for bloodborne pathogens, the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.
Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.
Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.
In 2015, the Texas Department of State Health Services was notified that a hospital telemetry unit nurse had been reusing saline flush prefilled syringes in patients’ IV lines. Mistakenly believing that it was safe and that she was saving the hospital money, she had been reusing syringes for 6 months. This was not the hospital’s practice.
Because she had been putting patients at risk for bloodborne pathogens, the state, regional, and local health departments with consultation from the CDC worked with the hospital to investigate. The hospital notified 392 patients, advising them of potential exposure and offering them free testing for hepatitis B (HBV), hepatitis C (HCV), and HIV. A year after the exposure, 262 had completed initial screening and 182 had completed all recommended testing.
Two patients had newly diagnosed HBV and 2 had HCV. A patient with known preexisting chronic HCV infection had been hospitalized on the telemetry unit on the same day as one of the patients with newly diagnosed HCV. That second patient did not share overlapping days with any patient with known HCV infection, nor did the 2 with newly diagnosed HBV infection share with each other or any other patient with a known HBV infection. No epidemiologic evidence linked the patients with newly diagnosed infections to a potential source patient. But when specimens were tested, the results indicated transmission linkage between the patient with chronic HCV infection and one of the patients with newly diagnosed HCV infection.
Taken together, the CDC concluded, the findings indicated that at least 1 HCV infection was “likely transmitted” in the telemetry unit as a result of the inappropriate reuse and sharing of syringes. The investigation, the CDC adds, illustrates a need for ongoing education and oversight of health care providers regarding safe injection practices.
VA Establishes Presumption of Service Connection for Camp Lejeune
Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.
The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.
The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.
The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.
Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.
The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.
The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.
The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.
Veterans who were exposed to contaminated water at Camp Lejeune are now eligible for VA care and benefits if they have been diagnosed with any of 8 diseases: adult leukemia, aplastic anemia and other myelodysplastic syndromes, bladder cancer, kidney cancer, liver cancer, multiple myeloma, non-Hodgkin lymphoma, and Parkinson disease. The presumption of service connection regulations went into effect March 14.
The newly effective rule complements the health care already provided for 15 illnesses or conditions as part of the Honoring America’s Veterans and Caring for Camp Lejeune Families Act of 2012. The Camp Lejeune Act requires the VA to provide health care to veterans who served at Camp Lejeune and to reimburse family members or pay providers for medical expenses for those who lived there for ≥ 30 days between August 1, 1953, and December 31, 1987.
The act and new rule relate to 2 on-base water wells that were contaminated with trichloroethylene, perchloroethylene, benzene, vinyl chloride, and other compounds. The wells were shut down in 1985.
The presumption of service connection applies to active-duty, reserve, and National Guard members. The presumption also includes all of Camp Lejeune, Marine Corps Air Station New River, as well as satellite camps and housing areas.
Eliminating hepatitis in the United States: A road map
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
FROM THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE
Vaccination reduces risk of flu-associated pediatric deaths
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“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
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“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
.
“These results support current recommendations for annual influenza vaccination for all children 6 months of age” and older, wrote Brendan Flannery, PhD, and his coauthors at the Centers for Disease Control and Prevention, Atlanta. “To our knowledge, this is the first study to use laboratory-confirmed outcomes to investigate influenza vaccine effectiveness against influenza-associated deaths.”
“Best estimates based on [National Health Interview Survey] data suggested that vaccination reduced the risk of influenza-associated death by half among children with high-risk conditions and by nearly two-thirds among children without high-risk conditions,” Dr. Flannery and his coauthors reported.
Of 358 cases of pediatric death (aged 6 months to 17 years) confirmed to be associated with influenza, 75 (26%) had been vaccinated prior to their disease onset. The case-cohort analysis compared the 358 cases against three cohorts of U.S. children and adolescents: a telephone survey, a household survey, and a health insurance claims database.
The researchers had examined cases that were reported to the U.S. Influenza-Associated Pediatric Mortality Surveillance System from July 2010 to June 2014. They excluded cases of children not yet eligible to be vaccinated or whose disease onset may have occurred before their vaccine had 14 days to take full effect (Pediatrics. 2017 Apr. doi: 10.1542/peds.2016-4244).
FROM PEDIATRICS
Latest weekly flu data show no decline in visits
Outpatient visits for influenza-like illness (ILI) held steady for the week ending March 25, but the number of states at the “high” range of activity dropped from 12 from 10 the previous week, according to the Centers for Disease Prevention and Control.
The proportion of outpatient visits for ILI was 3.2% for the second consecutive week, which halted the slowdown in activity that began the week ending Feb. 18. That 3.2% represents just under 25,000 visits for ILI of the almost 747,000 total visits reported to the Outpatient Influenza-like Illness Surveillance Network (ILINet) for the week ending March 25. By age, the largest groups with ILI visits for the week were individuals aged 5-24 years (41%) and those aged 4 years and under (20%), the CDC reported.
There were six flu-related pediatric deaths reported during the week ending March 25, but all occurred in earlier weeks. The total number of such deaths is now 61 for the 2016-2017 season, the CDC said.
Outpatient visits for influenza-like illness (ILI) held steady for the week ending March 25, but the number of states at the “high” range of activity dropped from 12 from 10 the previous week, according to the Centers for Disease Prevention and Control.
The proportion of outpatient visits for ILI was 3.2% for the second consecutive week, which halted the slowdown in activity that began the week ending Feb. 18. That 3.2% represents just under 25,000 visits for ILI of the almost 747,000 total visits reported to the Outpatient Influenza-like Illness Surveillance Network (ILINet) for the week ending March 25. By age, the largest groups with ILI visits for the week were individuals aged 5-24 years (41%) and those aged 4 years and under (20%), the CDC reported.
There were six flu-related pediatric deaths reported during the week ending March 25, but all occurred in earlier weeks. The total number of such deaths is now 61 for the 2016-2017 season, the CDC said.
Outpatient visits for influenza-like illness (ILI) held steady for the week ending March 25, but the number of states at the “high” range of activity dropped from 12 from 10 the previous week, according to the Centers for Disease Prevention and Control.
The proportion of outpatient visits for ILI was 3.2% for the second consecutive week, which halted the slowdown in activity that began the week ending Feb. 18. That 3.2% represents just under 25,000 visits for ILI of the almost 747,000 total visits reported to the Outpatient Influenza-like Illness Surveillance Network (ILINet) for the week ending March 25. By age, the largest groups with ILI visits for the week were individuals aged 5-24 years (41%) and those aged 4 years and under (20%), the CDC reported.
There were six flu-related pediatric deaths reported during the week ending March 25, but all occurred in earlier weeks. The total number of such deaths is now 61 for the 2016-2017 season, the CDC said.
Osimertinib receives full approval for advanced EGFR-mutated NSCLC
The Food and Drug Administration has converted accelerated approval of osimertinib to full approval for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.
Also included in the indication, disease must have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy, the FDA said in a statement.
Full approval was based on an improvement in progression-free survival (PFS) in the phase III AURA3 study, which randomized 419 patients (2:1) to receive osimertinib (n = 279) 80 mg orally once daily or platinum-based doublet chemotherapy (n = 140). The hazard ratio for the investigator-assessed PFS was .30 (95% confidence interval: 0.23, 0.41; P less than .001).
The estimated median PFS was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Confirmed ORR was 65% (95% CI: 59%, 70%) and 29% (95% CI: 21%, 37%) in the osimertinib and chemotherapy arms, respectively (P less than .0001). Estimated median response durations were 11 months (95% CI: 8.6, 12.6) and 4.2 months (95% CI: 3.9, 5.9) in the osimertinib and chemotherapy arms, respectively, according to the FDA statement.
Overall survival data are immature, the FDA said.
All patients had metastatic EGFR T790M mutation–positive NSCLC, identified by the cobas EGFR mutation test performed in a central laboratory, and progressive disease following first-line EGFR TKI therapy. Patients in the chemotherapy arm received either pemetrexed, 500 mg/m2 with carboplatin AUC5, or pemetrexed, 500mg/m2 with cisplatin 75 mg/m2), on day 1 of every 21-day cycle for up to six cycles followed by pemetrexed maintenance therapy.
The most serious adverse reactions, evaluated in 833 patients receiving osimertinib, were interstitial lung disease/pneumonitis (3.5%), QTc interval prolongation (0.7%), cardiomyopathy (1.9%), and keratitis (0.7%). The most common adverse reactions were diarrhea, rash, dry skin, nail toxicity, and fatigue.
The recommended dose of osimertinib, to be marketed as Tagrisso by AstraZeneca, is 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. The presence of an EGFR T790M mutation in a tumor specimen, or plasma specimen (if tumor tissue is unavailable), should be confirmed by an FDA-approved test prior to initiation of treatment.
Full prescribing information is available here.
The Food and Drug Administration has converted accelerated approval of osimertinib to full approval for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.
Also included in the indication, disease must have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy, the FDA said in a statement.
Full approval was based on an improvement in progression-free survival (PFS) in the phase III AURA3 study, which randomized 419 patients (2:1) to receive osimertinib (n = 279) 80 mg orally once daily or platinum-based doublet chemotherapy (n = 140). The hazard ratio for the investigator-assessed PFS was .30 (95% confidence interval: 0.23, 0.41; P less than .001).
The estimated median PFS was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Confirmed ORR was 65% (95% CI: 59%, 70%) and 29% (95% CI: 21%, 37%) in the osimertinib and chemotherapy arms, respectively (P less than .0001). Estimated median response durations were 11 months (95% CI: 8.6, 12.6) and 4.2 months (95% CI: 3.9, 5.9) in the osimertinib and chemotherapy arms, respectively, according to the FDA statement.
Overall survival data are immature, the FDA said.
All patients had metastatic EGFR T790M mutation–positive NSCLC, identified by the cobas EGFR mutation test performed in a central laboratory, and progressive disease following first-line EGFR TKI therapy. Patients in the chemotherapy arm received either pemetrexed, 500 mg/m2 with carboplatin AUC5, or pemetrexed, 500mg/m2 with cisplatin 75 mg/m2), on day 1 of every 21-day cycle for up to six cycles followed by pemetrexed maintenance therapy.
The most serious adverse reactions, evaluated in 833 patients receiving osimertinib, were interstitial lung disease/pneumonitis (3.5%), QTc interval prolongation (0.7%), cardiomyopathy (1.9%), and keratitis (0.7%). The most common adverse reactions were diarrhea, rash, dry skin, nail toxicity, and fatigue.
The recommended dose of osimertinib, to be marketed as Tagrisso by AstraZeneca, is 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. The presence of an EGFR T790M mutation in a tumor specimen, or plasma specimen (if tumor tissue is unavailable), should be confirmed by an FDA-approved test prior to initiation of treatment.
Full prescribing information is available here.
The Food and Drug Administration has converted accelerated approval of osimertinib to full approval for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer (NSCLC), as detected by an FDA-approved test.
Also included in the indication, disease must have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy, the FDA said in a statement.
Full approval was based on an improvement in progression-free survival (PFS) in the phase III AURA3 study, which randomized 419 patients (2:1) to receive osimertinib (n = 279) 80 mg orally once daily or platinum-based doublet chemotherapy (n = 140). The hazard ratio for the investigator-assessed PFS was .30 (95% confidence interval: 0.23, 0.41; P less than .001).
The estimated median PFS was 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Confirmed ORR was 65% (95% CI: 59%, 70%) and 29% (95% CI: 21%, 37%) in the osimertinib and chemotherapy arms, respectively (P less than .0001). Estimated median response durations were 11 months (95% CI: 8.6, 12.6) and 4.2 months (95% CI: 3.9, 5.9) in the osimertinib and chemotherapy arms, respectively, according to the FDA statement.
Overall survival data are immature, the FDA said.
All patients had metastatic EGFR T790M mutation–positive NSCLC, identified by the cobas EGFR mutation test performed in a central laboratory, and progressive disease following first-line EGFR TKI therapy. Patients in the chemotherapy arm received either pemetrexed, 500 mg/m2 with carboplatin AUC5, or pemetrexed, 500mg/m2 with cisplatin 75 mg/m2), on day 1 of every 21-day cycle for up to six cycles followed by pemetrexed maintenance therapy.
The most serious adverse reactions, evaluated in 833 patients receiving osimertinib, were interstitial lung disease/pneumonitis (3.5%), QTc interval prolongation (0.7%), cardiomyopathy (1.9%), and keratitis (0.7%). The most common adverse reactions were diarrhea, rash, dry skin, nail toxicity, and fatigue.
The recommended dose of osimertinib, to be marketed as Tagrisso by AstraZeneca, is 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. The presence of an EGFR T790M mutation in a tumor specimen, or plasma specimen (if tumor tissue is unavailable), should be confirmed by an FDA-approved test prior to initiation of treatment.
Full prescribing information is available here.