©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

©ASCO/Zach Boyden-Holmes 2018

CHICAGO—A specific gene signature might be able to identify patients at risk of CD19 CAR T-cell associated neurotoxicity, according to results of an exploratory analysis presented at the 2018 ASCO Annual Meeting.

The analysis, based on bone marrow samples from patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) treated with JCAR015 in the ROCKET trial, helped identify a set of neurotoxicity-associated genes that separated patients based on molecular subtype.

“These findings suggest that patient risk stratification by molecular subtype of disease or gene expression signature may play a role in identifying patients at elevated risk of neurotoxicity,” said Jae Park, MD, of Memorial Sloan Kettering Cancer Center, New York, New York, in a presentation of the findings (abstract 7007).

The phase 2 ROCKET study included adult patients with relapsed or refractory morphological (>5% blasts in bone marrow) CD-19 positive disease in first salvage or greater, including post allogeneic hematopoietic stem cell transplantation (HSCT). Prior blinatumomab was allowed.

The tumor gene expression study presented at ASCO was based on sequenced RNA from pre-apheresis bone marrow samples available for 31 patients in the ROCKET study.

Investigators identified a set of 10 genes expressed more frequently in bone marrow samples from patients in ROCKET with low (grade 0-1) neurotoxicity, and 7 that were more frequent in those who had severe (grade 4-5) neurotoxicity.

Looking at B-cell ALL samples in public datasets by molecular subtype, they found genes highly expressed in the low neurotoxicity ROCKET patients were also highly expressed in Philadelphia chromosome-positive (Ph+) and Ph-like subtypes.

Conversely, the genes highly expressed in the severe neurotoxicity patients were also highly expressed in non-Ph-like samples.

A total of 16 ROCKET patients were classified as having Ph-like gene expression and 15 as having non-Ph-like expression.

There were no grade 4-5 neurotoxicity events in the Ph-like patients, while both grade 3+ and grade 4+ neurotoxicity were significantly more prevalent in the non-Ph-like patients, investigators reported.

One of the most differentially expressed genes in the set was CCL17, which was higher in the low-neurotoxicity tumor samples, and likewise highly expressed in Ph-like B-cell ALL, according to the report.

“[CCL17] may serve as an early biomarker for differentiating severe neurotoxicity,” Dr Park said.

These findings are now being validated in the previously mentioned data set, as well as other studies to see if the findings can be replicated, according to Dr Park.

Juno Therapeutics, a Celgene company, shut down the phase 2 ROCKET trial of JCAR015 in 2017 after 2 clinical holds in 2016 and 5 patient deaths. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

Image from NIAID

The US Food and Drug Administrated (FDA) placed a clinical hold on the phase 1 trial of the Sleeping Beauty (SB)-generated CAR T-cell therapy in relapsed or refractory leukemia and lymphoma patients.

The Sleeping Beauty platform was designed to very rapidly manufacture CD19-specific CAR T cells at the point of care.

All SB-CAR T-cell processing is planned to take place within 2 days at the healthcare facility, thus eliminating shipping cells from hospitals to production sites and back again.

The FDA is requesting more chemistry, manufacturing, and control (CMC) information before allowing the trial to proceed.

The Sleeping Beauty technology, a non-viral transposon/transposase system, has the potential to reduce the costs and complexity associated with recombinant viral vector-based immunotherapy, according to developers.

Ziopharm Oncology, Precigen, Inc, a wholly owned subsidiary of Intrexon Corporation, and the University of Texas MD Anderson Cancer Center, are developing the Sleeping Beauty CAR T cell therapy.

“We know what is needed to address the hold issues and are looking forward to responding to the agency in a timely manner,” said Laurence Cooper, MD, PhD, chief executive officer of Ziopharm, in a corporate release.

“We are undertaking cutting-edge science and are on the verge of a paradigm shift based on our approach to very rapidly manufacture CD19-specific T cells within 2 days using our non-viral approach to CAR-T therapy based on the Sleeping Beauty platform.”

The phase 1 trial in question is a third-generation trial in which the CAR T cells are designed to co-express CD19-specific CAR, membrane-bound interleukin 15, and a safety switch.

The findings from earlier generation phase 1 trials have been previously reported in The Journal of Clinical Investigation. 

A case of inflammatory myopathy in an immunosuppressed patient who received a tattoo highlights a possible risk of tattooing in people with a compromised immune system.

Writing in the June 18 online edition of BMJ Case Reports, clinicians described a 31-year-old woman who was on long-term immunosuppressive therapy after bilateral lung transplants for cystic fibrosis.

The woman received a large, colored tattoo on her upper leg, with no immediate complications beyond the usual mild skin irritation. However, 9 days later, she developed pain in her left thigh and knee that was severe enough to require analgesic treatment that included tramadol and paracetamol.

The pain settled over the following few months, but the woman continued to experience a sense of fullness from her hip to knee along the medial side of her thigh. She presented to a rheumatology clinic 10 months after she was tattooed, with pain that was still constant and disturbing her sleep, but with no apparent aggravating factors and, otherwise, she was in good health.

Work-up included an MRI that showed focal inflammation of the vastus medialis muscle, particularly in the distal third, but a biopsy found no bacterial growth, nor was there any bacterial or fungal infection found in fluid drawn from the knee. However, histopathology revealed scattered internal nuclei, atrophic fibers, a mild perivascular inflammatory infiltrate, and upregulation of human leukocyte antigen.

In the report, William T. Wilson, MD, and his colleagues from the department of trauma and orthopedics, NHS Greater Glasgow and Clyde, Glasgow, said that these findings gave the impression of an inflammatory myopathy in which the pathologic response may have been influenced by the immunosuppression.

“To our knowledge, there have been no previously reported cases of tattoo-associated reactions causing an inflammatory myopathy,” they wrote. “This could be a rare occurrence or represent an underdiagnosis for patients presenting with similar symptoms having had tattoos.”

The authors suggested there was a chance that the myopathy may have been stimulated by a toxin or pathogen introduced during tattoo procedure. However, they pointed out that they could not identify a causative pathogen, although the timing of onset and location of symptoms correlated with the tattoo application.

“This case serves as a reminder to consider tattoo-related complications as part of the differential diagnosis when patients, especially the immune-suppressed, present with unusual atraumatic musculoskeletal symptoms,” they wrote.

After the biopsy, the woman received physiotherapy in the form of basic quadriceps-strengthening exercises. Her condition did not start to improve until about 1 year after the onset of symptoms, and by 3 years, she had no more pain and had resumed normal activities.

No funding or conflicts of interest were declared.

SOURCE: Wilson W et al. BMJ Case Rep. 2018. Jun 18. doi: 10.1136/bcr-2018-224968.

A case of inflammatory myopathy in an immunosuppressed patient who received a tattoo highlights a possible risk of tattooing in people with a compromised immune system.

Writing in the June 18 online edition of BMJ Case Reports, clinicians described a 31-year-old woman who was on long-term immunosuppressive therapy after bilateral lung transplants for cystic fibrosis.

The woman received a large, colored tattoo on her upper leg, with no immediate complications beyond the usual mild skin irritation. However, 9 days later, she developed pain in her left thigh and knee that was severe enough to require analgesic treatment that included tramadol and paracetamol.

The pain settled over the following few months, but the woman continued to experience a sense of fullness from her hip to knee along the medial side of her thigh. She presented to a rheumatology clinic 10 months after she was tattooed, with pain that was still constant and disturbing her sleep, but with no apparent aggravating factors and, otherwise, she was in good health.

Work-up included an MRI that showed focal inflammation of the vastus medialis muscle, particularly in the distal third, but a biopsy found no bacterial growth, nor was there any bacterial or fungal infection found in fluid drawn from the knee. However, histopathology revealed scattered internal nuclei, atrophic fibers, a mild perivascular inflammatory infiltrate, and upregulation of human leukocyte antigen.

In the report, William T. Wilson, MD, and his colleagues from the department of trauma and orthopedics, NHS Greater Glasgow and Clyde, Glasgow, said that these findings gave the impression of an inflammatory myopathy in which the pathologic response may have been influenced by the immunosuppression.

“To our knowledge, there have been no previously reported cases of tattoo-associated reactions causing an inflammatory myopathy,” they wrote. “This could be a rare occurrence or represent an underdiagnosis for patients presenting with similar symptoms having had tattoos.”

The authors suggested there was a chance that the myopathy may have been stimulated by a toxin or pathogen introduced during tattoo procedure. However, they pointed out that they could not identify a causative pathogen, although the timing of onset and location of symptoms correlated with the tattoo application.

“This case serves as a reminder to consider tattoo-related complications as part of the differential diagnosis when patients, especially the immune-suppressed, present with unusual atraumatic musculoskeletal symptoms,” they wrote.

After the biopsy, the woman received physiotherapy in the form of basic quadriceps-strengthening exercises. Her condition did not start to improve until about 1 year after the onset of symptoms, and by 3 years, she had no more pain and had resumed normal activities.

No funding or conflicts of interest were declared.

SOURCE: Wilson W et al. BMJ Case Rep. 2018. Jun 18. doi: 10.1136/bcr-2018-224968.

A case of inflammatory myopathy in an immunosuppressed patient who received a tattoo highlights a possible risk of tattooing in people with a compromised immune system.

Writing in the June 18 online edition of BMJ Case Reports, clinicians described a 31-year-old woman who was on long-term immunosuppressive therapy after bilateral lung transplants for cystic fibrosis.

The woman received a large, colored tattoo on her upper leg, with no immediate complications beyond the usual mild skin irritation. However, 9 days later, she developed pain in her left thigh and knee that was severe enough to require analgesic treatment that included tramadol and paracetamol.

The pain settled over the following few months, but the woman continued to experience a sense of fullness from her hip to knee along the medial side of her thigh. She presented to a rheumatology clinic 10 months after she was tattooed, with pain that was still constant and disturbing her sleep, but with no apparent aggravating factors and, otherwise, she was in good health.

Work-up included an MRI that showed focal inflammation of the vastus medialis muscle, particularly in the distal third, but a biopsy found no bacterial growth, nor was there any bacterial or fungal infection found in fluid drawn from the knee. However, histopathology revealed scattered internal nuclei, atrophic fibers, a mild perivascular inflammatory infiltrate, and upregulation of human leukocyte antigen.

In the report, William T. Wilson, MD, and his colleagues from the department of trauma and orthopedics, NHS Greater Glasgow and Clyde, Glasgow, said that these findings gave the impression of an inflammatory myopathy in which the pathologic response may have been influenced by the immunosuppression.

“To our knowledge, there have been no previously reported cases of tattoo-associated reactions causing an inflammatory myopathy,” they wrote. “This could be a rare occurrence or represent an underdiagnosis for patients presenting with similar symptoms having had tattoos.”

The authors suggested there was a chance that the myopathy may have been stimulated by a toxin or pathogen introduced during tattoo procedure. However, they pointed out that they could not identify a causative pathogen, although the timing of onset and location of symptoms correlated with the tattoo application.

“This case serves as a reminder to consider tattoo-related complications as part of the differential diagnosis when patients, especially the immune-suppressed, present with unusual atraumatic musculoskeletal symptoms,” they wrote.

After the biopsy, the woman received physiotherapy in the form of basic quadriceps-strengthening exercises. Her condition did not start to improve until about 1 year after the onset of symptoms, and by 3 years, she had no more pain and had resumed normal activities.

No funding or conflicts of interest were declared.

SOURCE: Wilson W et al. BMJ Case Rep. 2018. Jun 18. doi: 10.1136/bcr-2018-224968.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

Rural cancer survivors reported more timely care than did urban cancer survivors in a survey of 6,826 Medicare beneficiaries.

Taken as a whole, a similar quality of care was reported between the two groups, but the picture changed when racial/ethnic subgroups were considered. Non-Hispanic black and Hispanic patients in rural locations reported inferior care to their urban counterparts, investigators wrote in Cancer.

“Cancer patients living in rural areas are vulnerable and have unique health care needs,” wrote lead author Michelle A. Mollica, PhD, of the National Cancer Institute, and her colleagues. “To our knowledge, this is the first study to explore the patient’s perception of the timeliness of care in such a large, multiregion sample of cancer patients.”

In 2003, the National Academy of Medicine concluded that living in a rural environment was associated with poorer health. Existing research surrounding cancer has echoed this concern, showing that rural patients have higher rates of cancer and mortality, longer delays in diagnosis, and limited access to care.

The current, retrospective study involved 6,140 urban and 686 rural Medicare beneficiaries who were aged at least 65 years when diagnosed with either breast, lung, colorectal, or prostate cancer. Consumer Assessment of Healthcare Providers and Systems surveys were conducted between 1998 and 2013, then linked with data from the Surveillance, Epidemiology, and End Results registry program.

Surveys were conducted within 12 months of diagnosis, during which time patients were asked about their access to care as defined by two composites: “Getting Needed Care” and “Getting Care Quickly.” Getting Needed Care included ease of making appointments and receiving treatments and Getting Care Quickly questions asked about appointment delays and time spent waiting at the doctor’s office. Answers were converted to a numerical score from 0 to 100, with 0 being the worst and 100 being the best.

For both composites, mean scores for urban and rural locations were greater than 85 out of 100.

In contrast to previous studies, urban patients reported longer delays in care, scoring Getting Care Quickly 2.27 points lower than rural patients (P = .02). Pacific Islanders and non-Hispanic Asian patients from rural places reported even faster care, ranking about 8 points higher than urban patients of the same race/ethnicity.

Locality did not have a significant impact on Getting Needed Care unless race/ethnicity was also considered (P = .04). Non-Hispanic white patients from rural locations scored Getting Needed Care about 2 points higher than urban white patients, while Hispanic and non-Hispanic black patients had an opposite trend, with this rural cohort ranking Getting Needed Care lower than urban patients of the same race/ethnicity.

“Geographic residence is but one important factor in cancer care delivery,” the authors noted. “There is a need for fine-grained research looking at specific barriers for urban residents, experiences of racial/ethnic minority survivors residing in rural areas, and rural-urban differences in the clinic settings in which medical care is delivered.”

The authors had no disclosures to report.

SOURCE: Mollica MA et al. Cancer. 2018 Jun 7. doi: 10.1002/cncr.31541.

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Patients with type 2 diabetes mellitus have an increased risk of developing Parkinson’s disease later in life, according to an investigation published online ahead of print June 13 in Neurology. The magnitude of risk is greater in younger patients and in patients with complications from diabetes.

Investigators have hypothesized an association between diabetes and the risk of Parkinson’s disease, but studies of the potential link have had conflicting results. Thomas T. Warner, MD, PhD, Professor of Clinical Neurology at University College London (UCL), and colleagues conducted a retrospective cohort study to examine this question anew.

Analyzing a Nationwide Hospital Database

The researchers reviewed English national Hospital Episode Statistics and mortality data collected between 1999 and 2011 and created a cohort of 2,017,115 patients who had been admitted for hospital care with a diagnosis of type 2 diabetes. They created a reference cohort of 6,173,208 patients without diabetes who were admitted for minor medical and surgical procedures. Conditions in this cohort included sprains, inguinal hernia, bruising, and hip replacement. People with Parkinson’s disease, ischemic cerebral infarction, vascular parkinsonism, drug-induced secondary parkinsonism, and normal pressure hydrocephalus were excluded from the study. Dr. Warner and colleagues created multivariable Cox proportional hazard regression models to estimate the risk of subsequent Parkinson’s disease.

Participants with diabetes had a greater risk of a subsequent diagnosis of Parkinson’s disease than patients in the reference cohort (adjusted hazard ratio [HR], 1.32). In subgroup analyses, the researchers found that the risk was substantially higher among patients between ages 25 and 44 (adjusted HR, 3.81) and those with complicated diabetes (adjusted HR, 1.49). Genetic factors may exert a relatively greater effect on younger people, and this difference may account for the increased risk among younger participants with diabetes, said the authors.

The adjusted HR of Parkinson’s disease was 1.40 in patients with diabetes between ages 65 and 74 and 1.18 in those age 75 or older. “The association in elderly patients may be the consequence of disrupted insulin signaling secondary to additional lifestyle and environmental factors causing cumulative pathogenic brain changes,” said Dr. Warner and colleagues.

No Adjustment for Potential Confounders

The large size of the database and the ability to exclude people with cerebrovascular disease and drug-induced and vascular parkinsonisms were among the study’s main strengths, according to the authors. Its weaknesses included an inability to adjust for potential confounders and the lack of clinical information about Parkinson’s disease ascertainment beyond routinely collected data.

The results could help researchers identify “new ways to treat or prevent the development of Parkinson’s disease, such as use of antidiabetes drugs to restore the brain’s insulin signaling,” said Dr. Warner. “A UCL-led study published last year found that a drug commonly used to treat diabetes shows promise in not only relieving Parkinson’s disease symptoms, but potentially altering the course of the disease itself. What we do not know is whether trying to treat people with type 2 diabetes better would reduce the risk of developing Parkinson’s disease.”

—Erik Greb

Suggested Reading

De Pablo-Fernandez E, Goldacre R, Pakpoor J, et al. Association between diabetes and subsequent Parkinson disease: a record-linkage cohort study. Neurology. 2018 Jun 13 [Epub ahead of print].

Patients with type 2 diabetes were significantly less likely to develop or die from cardiovascular disease when they followed a healthy lifestyle, according to the results of a pooled analysis of two large observational cohort studies.

Relevant criteria included following a high-quality diet, not smoking, exercising moderately to vigorously for at least 2.5 hours per week, and limiting alcohol intake to 5-15 g of alcohol per day for women or 5-30 g/day for men. After the researchers controlled for possible confounders, individuals who met at least three of these criteria had about a 52% lower risk of new-onset CVD (adjusted hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and a 68% lower risk of CVD-related mortality (HR, 0.32; 95% CI, 0.22-0.47), said Gang Liu, PhD, of Harvard T.H. Chan School of Public Health, Boston, and his associates. “Further research is needed to identify the most effective strategies to encourage patients with diabetes to adopt and maintain a healthy lifestyle,” they wrote. The report was published online June 18 in the Journal of the American College of Cardiology.

Cardiovascular disease is common in type 2 diabetes (T2DM), but few studies have examined the possible mitigating effects of healthy lifestyle. For this study, the researchers analyzed questionnaire data for 11,527 participants with T2DM diagnosed after enrollment in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. Over an average follow-up time of 13.3 years, there were 2,311 incident cases of CVD, including 498 cases of stroke, and 858 deaths from CVD. The reduced risk of cardiovascular events remained significant even after the researchers controlled for factors such as body mass index, hypertension, hypercholesterolemia, use of antihypertensive agents, cholesterol lowering drugs, diabetes medication, and hemoglobin A_1c.

pojoslaw/ThinkStock

Healthy lifestyle also was associated with significant reductions in the individual risk of coronary heart disease (HR, 0.53) and stroke (HR, 0.33), the investigators said. In this population, 40% of the risk of CVD mortality could be attributed to poor adherence to a healthy lifestyle, they added. Importantly, individuals who improved their lifestyle after a T2DM diagnosis had a significantly lower risk of CVD and CVD mortality than those who did not. The findings, they concluded, “support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2DM.”

The National Institutes of Health provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Liu G et al. J Am Coll Cardiol. 2018;71:2867-76. doi: 10.1016/j.jacc.2018.04.027.

Patients with type 2 diabetes were significantly less likely to develop or die from cardiovascular disease when they followed a healthy lifestyle, according to the results of a pooled analysis of two large observational cohort studies.

Relevant criteria included following a high-quality diet, not smoking, exercising moderately to vigorously for at least 2.5 hours per week, and limiting alcohol intake to 5-15 g of alcohol per day for women or 5-30 g/day for men. After the researchers controlled for possible confounders, individuals who met at least three of these criteria had about a 52% lower risk of new-onset CVD (adjusted hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and a 68% lower risk of CVD-related mortality (HR, 0.32; 95% CI, 0.22-0.47), said Gang Liu, PhD, of Harvard T.H. Chan School of Public Health, Boston, and his associates. “Further research is needed to identify the most effective strategies to encourage patients with diabetes to adopt and maintain a healthy lifestyle,” they wrote. The report was published online June 18 in the Journal of the American College of Cardiology.

Cardiovascular disease is common in type 2 diabetes (T2DM), but few studies have examined the possible mitigating effects of healthy lifestyle. For this study, the researchers analyzed questionnaire data for 11,527 participants with T2DM diagnosed after enrollment in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. Over an average follow-up time of 13.3 years, there were 2,311 incident cases of CVD, including 498 cases of stroke, and 858 deaths from CVD. The reduced risk of cardiovascular events remained significant even after the researchers controlled for factors such as body mass index, hypertension, hypercholesterolemia, use of antihypertensive agents, cholesterol lowering drugs, diabetes medication, and hemoglobin A_1c.

pojoslaw/ThinkStock

Healthy lifestyle also was associated with significant reductions in the individual risk of coronary heart disease (HR, 0.53) and stroke (HR, 0.33), the investigators said. In this population, 40% of the risk of CVD mortality could be attributed to poor adherence to a healthy lifestyle, they added. Importantly, individuals who improved their lifestyle after a T2DM diagnosis had a significantly lower risk of CVD and CVD mortality than those who did not. The findings, they concluded, “support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2DM.”

The National Institutes of Health provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Liu G et al. J Am Coll Cardiol. 2018;71:2867-76. doi: 10.1016/j.jacc.2018.04.027.

Patients with type 2 diabetes were significantly less likely to develop or die from cardiovascular disease when they followed a healthy lifestyle, according to the results of a pooled analysis of two large observational cohort studies.

Relevant criteria included following a high-quality diet, not smoking, exercising moderately to vigorously for at least 2.5 hours per week, and limiting alcohol intake to 5-15 g of alcohol per day for women or 5-30 g/day for men. After the researchers controlled for possible confounders, individuals who met at least three of these criteria had about a 52% lower risk of new-onset CVD (adjusted hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and a 68% lower risk of CVD-related mortality (HR, 0.32; 95% CI, 0.22-0.47), said Gang Liu, PhD, of Harvard T.H. Chan School of Public Health, Boston, and his associates. “Further research is needed to identify the most effective strategies to encourage patients with diabetes to adopt and maintain a healthy lifestyle,” they wrote. The report was published online June 18 in the Journal of the American College of Cardiology.

Cardiovascular disease is common in type 2 diabetes (T2DM), but few studies have examined the possible mitigating effects of healthy lifestyle. For this study, the researchers analyzed questionnaire data for 11,527 participants with T2DM diagnosed after enrollment in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. Over an average follow-up time of 13.3 years, there were 2,311 incident cases of CVD, including 498 cases of stroke, and 858 deaths from CVD. The reduced risk of cardiovascular events remained significant even after the researchers controlled for factors such as body mass index, hypertension, hypercholesterolemia, use of antihypertensive agents, cholesterol lowering drugs, diabetes medication, and hemoglobin A_1c.

pojoslaw/ThinkStock

Healthy lifestyle also was associated with significant reductions in the individual risk of coronary heart disease (HR, 0.53) and stroke (HR, 0.33), the investigators said. In this population, 40% of the risk of CVD mortality could be attributed to poor adherence to a healthy lifestyle, they added. Importantly, individuals who improved their lifestyle after a T2DM diagnosis had a significantly lower risk of CVD and CVD mortality than those who did not. The findings, they concluded, “support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2DM.”

The National Institutes of Health provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Liu G et al. J Am Coll Cardiol. 2018;71:2867-76. doi: 10.1016/j.jacc.2018.04.027.

Hospitalists regularly treat patients with limited health literacy, and in many cases, the hospitalist may not even be aware of it. “Patients are unlikely to know or, more importantly, disclose their limited health literacy status,” according to a recent study.¹ But hospitalists certainly see its effects: Limited health literacy often results in poor outcomes and high rates of readmittance.

“We know patients with limited health literacy are common and that they have poor health outcomes,” said study coauthor Robert Leverence, MD. “We also know there are ways to mitigate those outcomes. For that reason, we believe screening is important. In our study, we showed such routine screening is feasible in a large teaching hospital.”

The study describes the implementation of a hospital-wide routine health literacy assessment at an academic medical center initiated by nurses and applied to all adult inpatients. “We incorporated the health literacy screen and care plan into our electronic health record,” the authors wrote. “When a patient screens positive for limited health literacy, two automated responses are triggered: a one-time alert on chart entry for all users ... and a nursing care plan containing relevant educational recommendations.”

“To me it is a cringe-worthy event to give a 10-page AVS to a patient who can’t read,” Dr. Leverence added. “Health literacy screening allows us to tailor the discharge process to meet the needs of the individual patient. Once these patients are identified, then appropriate efforts can be efficiently deployed.”

Those efforts might include, at discharge, offering easy-to-read materials and teach-back, and having a caregiver in the room and a pharmacist performing bedside medication education.
 

Reference

1. Warring C, Pinkney J, Delvo-Favre E, et al. “Implementation of a Routine Health Literacy Assessment at an Academic Medical Center.” J Healthc Qual. doi: 10.1097/JHQ.0000000000000116

Hospitalists regularly treat patients with limited health literacy, and in many cases, the hospitalist may not even be aware of it. “Patients are unlikely to know or, more importantly, disclose their limited health literacy status,” according to a recent study.¹ But hospitalists certainly see its effects: Limited health literacy often results in poor outcomes and high rates of readmittance.

“We know patients with limited health literacy are common and that they have poor health outcomes,” said study coauthor Robert Leverence, MD. “We also know there are ways to mitigate those outcomes. For that reason, we believe screening is important. In our study, we showed such routine screening is feasible in a large teaching hospital.”

The study describes the implementation of a hospital-wide routine health literacy assessment at an academic medical center initiated by nurses and applied to all adult inpatients. “We incorporated the health literacy screen and care plan into our electronic health record,” the authors wrote. “When a patient screens positive for limited health literacy, two automated responses are triggered: a one-time alert on chart entry for all users ... and a nursing care plan containing relevant educational recommendations.”

“To me it is a cringe-worthy event to give a 10-page AVS to a patient who can’t read,” Dr. Leverence added. “Health literacy screening allows us to tailor the discharge process to meet the needs of the individual patient. Once these patients are identified, then appropriate efforts can be efficiently deployed.”

Those efforts might include, at discharge, offering easy-to-read materials and teach-back, and having a caregiver in the room and a pharmacist performing bedside medication education.
 

Reference

1. Warring C, Pinkney J, Delvo-Favre E, et al. “Implementation of a Routine Health Literacy Assessment at an Academic Medical Center.” J Healthc Qual. doi: 10.1097/JHQ.0000000000000116

Hospitalists regularly treat patients with limited health literacy, and in many cases, the hospitalist may not even be aware of it. “Patients are unlikely to know or, more importantly, disclose their limited health literacy status,” according to a recent study.¹ But hospitalists certainly see its effects: Limited health literacy often results in poor outcomes and high rates of readmittance.

“We know patients with limited health literacy are common and that they have poor health outcomes,” said study coauthor Robert Leverence, MD. “We also know there are ways to mitigate those outcomes. For that reason, we believe screening is important. In our study, we showed such routine screening is feasible in a large teaching hospital.”

The study describes the implementation of a hospital-wide routine health literacy assessment at an academic medical center initiated by nurses and applied to all adult inpatients. “We incorporated the health literacy screen and care plan into our electronic health record,” the authors wrote. “When a patient screens positive for limited health literacy, two automated responses are triggered: a one-time alert on chart entry for all users ... and a nursing care plan containing relevant educational recommendations.”

“To me it is a cringe-worthy event to give a 10-page AVS to a patient who can’t read,” Dr. Leverence added. “Health literacy screening allows us to tailor the discharge process to meet the needs of the individual patient. Once these patients are identified, then appropriate efforts can be efficiently deployed.”

Those efforts might include, at discharge, offering easy-to-read materials and teach-back, and having a caregiver in the room and a pharmacist performing bedside medication education.
 

Reference

1. Warring C, Pinkney J, Delvo-Favre E, et al. “Implementation of a Routine Health Literacy Assessment at an Academic Medical Center.” J Healthc Qual. doi: 10.1097/JHQ.0000000000000116

MALMO, SWEDEN – The unique 20-year U.S. experience with pediatric universal varicella vaccination hasn’t resulted in the anticipated increase in herpes zoster predicted by the exogenous boosting hypothesis, Lara J. Wolfson, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In fact, the opposite has occurred. And this finding – based upon hard data – should be of considerable interest to European health officials who have been considering introducing universal varicella vaccination into their national health care systems but have refrained because of theoretical concerns raised by the venerable exogenous boosting hypothesis, noted Dr. Wolfson, director of outcomes research at the Merck Center for Observational and Real-World Evidence, Kenilworth, N.J.

Bruce Jancin/MDedge News

The exogenous boosting hypothesis, which dates back to the mid-1960s, holds that reexposure to wild circulating varicella virus prevents development of herpes zoster later in life. Conversely, by vaccinating children against varicella, opportunities are diminished for reexposure to wild type virus among adults who weren’t vaccinated against varicella, so the hypothesis would predict an increase in the incidence of herpes zoster that should peak 15-35 years after introduction of universal varicella vaccination.

“The same virus that causes varicella in children later reactivates after going dormant in the dorsal root ganglia, and it reactivates as herpes zoster, which is 10 times more severe than chicken pox and leads to 10 times the health care costs. So if in fact implementing a universal varicella vaccine program would lead to an increased incidence of herpes zoster, this would be a bad thing,” the researcher explained.

However, the predictive models based upon the exogenous boosting hypothesis are built upon scanty data. And the models have great difficulty in adjusting for the changes in population dynamics that have occurred in the United States and Western Europe during the past quarter century: namely, declining birth rates coupled with survival to an older age.

Dr. Wolfson presented a retrospective study of deidentified administrative claims data from the MarketScan database covering roughly one-fifth of the U.S. population during 1991-2016. Her analysis broke down the annual incidence of varicella and herpes zoster in three eras: 1991-1995, which was the pre–varicella vaccination period; 1996-2006, when single-dose universal varicella vaccination of children was recommended; and 2007-2016, when two-dose vaccination became standard.

The first key study finding was that herpes zoster rates in the United States already were climbing across all age groups back in 1991-1995; that is, before introduction of universal varicella vaccination. Why? Probably because of those changes in population dynamics, although that’s speculative. The second key finding was that contrary to the exogenous boosting hypothesis prediction that the annual incidence of herpes zoster would accelerate after introduction of universal varicella vaccination, the rate of increase slowed, then plateaued during 2013-2016, most prominently in individuals aged 65 or older.

“In comparing the pre–universal varicella vaccination period to the one- or two-dose period or the total 20 years of vaccination, what we saw consistently across every age group is that herpes zoster is decelerating. There is actually less increase in the rate of herpes zoster than before varicella vaccination,” Dr. Wolfson said.

Uptake of the herpes zoster vaccine, introduced in the United States in 2008, was too low during the study years to account for this trend, she added.

Most dramatically, the incidence of herpes zoster among youths under age 18 years plummeted by 61.4%, from 88 per 100,000 person-years in 1991-1995 to 34 per 100,000 in 2016.

And of course, varicella disease has sharply declined in all age groups following the introduction of universal pediatric varicella vaccination, Dr. Wolfson observed.

Her study was supported by her employer, Merck.

[email protected]

MALMO, SWEDEN – The unique 20-year U.S. experience with pediatric universal varicella vaccination hasn’t resulted in the anticipated increase in herpes zoster predicted by the exogenous boosting hypothesis, Lara J. Wolfson, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In fact, the opposite has occurred. And this finding – based upon hard data – should be of considerable interest to European health officials who have been considering introducing universal varicella vaccination into their national health care systems but have refrained because of theoretical concerns raised by the venerable exogenous boosting hypothesis, noted Dr. Wolfson, director of outcomes research at the Merck Center for Observational and Real-World Evidence, Kenilworth, N.J.

Bruce Jancin/MDedge News

The exogenous boosting hypothesis, which dates back to the mid-1960s, holds that reexposure to wild circulating varicella virus prevents development of herpes zoster later in life. Conversely, by vaccinating children against varicella, opportunities are diminished for reexposure to wild type virus among adults who weren’t vaccinated against varicella, so the hypothesis would predict an increase in the incidence of herpes zoster that should peak 15-35 years after introduction of universal varicella vaccination.

“The same virus that causes varicella in children later reactivates after going dormant in the dorsal root ganglia, and it reactivates as herpes zoster, which is 10 times more severe than chicken pox and leads to 10 times the health care costs. So if in fact implementing a universal varicella vaccine program would lead to an increased incidence of herpes zoster, this would be a bad thing,” the researcher explained.

However, the predictive models based upon the exogenous boosting hypothesis are built upon scanty data. And the models have great difficulty in adjusting for the changes in population dynamics that have occurred in the United States and Western Europe during the past quarter century: namely, declining birth rates coupled with survival to an older age.

Dr. Wolfson presented a retrospective study of deidentified administrative claims data from the MarketScan database covering roughly one-fifth of the U.S. population during 1991-2016. Her analysis broke down the annual incidence of varicella and herpes zoster in three eras: 1991-1995, which was the pre–varicella vaccination period; 1996-2006, when single-dose universal varicella vaccination of children was recommended; and 2007-2016, when two-dose vaccination became standard.

The first key study finding was that herpes zoster rates in the United States already were climbing across all age groups back in 1991-1995; that is, before introduction of universal varicella vaccination. Why? Probably because of those changes in population dynamics, although that’s speculative. The second key finding was that contrary to the exogenous boosting hypothesis prediction that the annual incidence of herpes zoster would accelerate after introduction of universal varicella vaccination, the rate of increase slowed, then plateaued during 2013-2016, most prominently in individuals aged 65 or older.

“In comparing the pre–universal varicella vaccination period to the one- or two-dose period or the total 20 years of vaccination, what we saw consistently across every age group is that herpes zoster is decelerating. There is actually less increase in the rate of herpes zoster than before varicella vaccination,” Dr. Wolfson said.

Uptake of the herpes zoster vaccine, introduced in the United States in 2008, was too low during the study years to account for this trend, she added.

Most dramatically, the incidence of herpes zoster among youths under age 18 years plummeted by 61.4%, from 88 per 100,000 person-years in 1991-1995 to 34 per 100,000 in 2016.

And of course, varicella disease has sharply declined in all age groups following the introduction of universal pediatric varicella vaccination, Dr. Wolfson observed.

Her study was supported by her employer, Merck.

[email protected]

MALMO, SWEDEN – The unique 20-year U.S. experience with pediatric universal varicella vaccination hasn’t resulted in the anticipated increase in herpes zoster predicted by the exogenous boosting hypothesis, Lara J. Wolfson, PhD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

In fact, the opposite has occurred. And this finding – based upon hard data – should be of considerable interest to European health officials who have been considering introducing universal varicella vaccination into their national health care systems but have refrained because of theoretical concerns raised by the venerable exogenous boosting hypothesis, noted Dr. Wolfson, director of outcomes research at the Merck Center for Observational and Real-World Evidence, Kenilworth, N.J.

Bruce Jancin/MDedge News

The exogenous boosting hypothesis, which dates back to the mid-1960s, holds that reexposure to wild circulating varicella virus prevents development of herpes zoster later in life. Conversely, by vaccinating children against varicella, opportunities are diminished for reexposure to wild type virus among adults who weren’t vaccinated against varicella, so the hypothesis would predict an increase in the incidence of herpes zoster that should peak 15-35 years after introduction of universal varicella vaccination.

“The same virus that causes varicella in children later reactivates after going dormant in the dorsal root ganglia, and it reactivates as herpes zoster, which is 10 times more severe than chicken pox and leads to 10 times the health care costs. So if in fact implementing a universal varicella vaccine program would lead to an increased incidence of herpes zoster, this would be a bad thing,” the researcher explained.

However, the predictive models based upon the exogenous boosting hypothesis are built upon scanty data. And the models have great difficulty in adjusting for the changes in population dynamics that have occurred in the United States and Western Europe during the past quarter century: namely, declining birth rates coupled with survival to an older age.

Dr. Wolfson presented a retrospective study of deidentified administrative claims data from the MarketScan database covering roughly one-fifth of the U.S. population during 1991-2016. Her analysis broke down the annual incidence of varicella and herpes zoster in three eras: 1991-1995, which was the pre–varicella vaccination period; 1996-2006, when single-dose universal varicella vaccination of children was recommended; and 2007-2016, when two-dose vaccination became standard.

The first key study finding was that herpes zoster rates in the United States already were climbing across all age groups back in 1991-1995; that is, before introduction of universal varicella vaccination. Why? Probably because of those changes in population dynamics, although that’s speculative. The second key finding was that contrary to the exogenous boosting hypothesis prediction that the annual incidence of herpes zoster would accelerate after introduction of universal varicella vaccination, the rate of increase slowed, then plateaued during 2013-2016, most prominently in individuals aged 65 or older.

“In comparing the pre–universal varicella vaccination period to the one- or two-dose period or the total 20 years of vaccination, what we saw consistently across every age group is that herpes zoster is decelerating. There is actually less increase in the rate of herpes zoster than before varicella vaccination,” Dr. Wolfson said.

Uptake of the herpes zoster vaccine, introduced in the United States in 2008, was too low during the study years to account for this trend, she added.

Most dramatically, the incidence of herpes zoster among youths under age 18 years plummeted by 61.4%, from 88 per 100,000 person-years in 1991-1995 to 34 per 100,000 in 2016.

And of course, varicella disease has sharply declined in all age groups following the introduction of universal pediatric varicella vaccination, Dr. Wolfson observed.

Her study was supported by her employer, Merck.

[email protected]

Some people have nightmares of giant rats attacking from their basements, others encounter monsters from a Stephen King novel. My nightmares are of clinic where time is the beast pursuing me. In my nightmares, I’m running late and can’t get to my next patient, or I’m trapped somehow and unable to get to clinic at all.

liseykina/thinkstockphotos

Time demands that I provide patients access quickly, start clinic on time, double my speed to make up for add-ins, or worse, late patients. Time is a constant, relentless monster, one that has apparently infiltrated my subconscious. Yet, time is relative.

Over Memorial Day weekend, my wife and I flew from San Diego to Alaska. Somewhere between those places time transforms – early summer in San Diego becomes early spring in Alaska.

When we landed, daffodils were in bloom, buds on the alders were just arriving, and the sun struggled to warm the air to 50 degrees. The daytime defied gravity: it was daylight by 4 a.m. and still so after 11 p.m. We were the first visitors this season in our little cabin near Seward.

“Your hot water might take a bit to get hot,” our host, Jim, informed us. He wore a thick flannel shirt and Carhartt workman trousers. He leaned against the cabin’s door frame with one hand at the top and the other hanging from the weight of a DeWalt drill at his side. “I made these cabins myself,” he informed. I was anxious to move on, to unpack and start exploring, but every time I tried to break away from his conversation, he extended it. He shared how a cow and calf (that’s moose talk) had come through earlier that morning. Then he told us about working in the timber industry, starting by “pulling green chain” and working his way up to being the keeper of the saws. While he talked, I watched a raven drop down from the tall Sitka spruce to a branch just across from where we parked our car. Just behind Jim, the raven was not only watching, but also listening in on our conversation. Jim pointed, “That bit of snow over there was all that was left from the 12-foot-high snow earlier this year. It was an easy winter.” He then advised we should start our trip with a visit to Exit Glacier. It was reachable by road and an easy hike.

Leamus/iStock/Getty Images

Staying upright on the steep trail to the glacier’s Harding Icefield concentrates the mind. Looking down and across the glacial outwash, I imagined how the ice once thousands of feet above my head carved a valley from rock. Ice compacted so completely and so deep that only blue light escapes. Indeed, a glacier is just a pile of unmelted snow, thousands of years in the making. The Kenai fjords, deep enough that humpback whales swim there, were carved from granite – at glacial speed. Some of the rocks there contain fossils all the way from the tropics. They were transported by the Pacific tectonic plate that has rotated counterclockwise from the equator to Alaska over millions of years – at tectonic speed. Life here has a way of sharpening your focus, allowing you to see perspective as exists in nature. Alaska is so old that an ob.gyn. could have seen his or her first patient here – a mother with a stillborn child – at the Upward Sun River, 11,500 years ago, where in 2013, the fossil remains of a late-term fetus dating back to that time was discovered. It is indeed relative.

After a long hike, a crispy, hot halibut sandwich, we made it back to our cabin. There was no WiFi or reliable cell service, no TV, no Netflix. We read in bed by daylight. I slept soundly, despite the bright light. No nightmares. No monsters.

The next morning, as I sipped my steaming coffee on our porch, the raven didn’t waste much time to stop by. He paused before coming nearly eye to eye on the roof of the firewood shed in front of me. He looked me up and down and cackled. Not a cawh, not warning me of my intrusion, but rather a vocalization. He just wanted to strike up a conversation with the first guest of the season. He had nothing but time.

On our last night, I lit a fire with wood Jim had cut for us (with help from lots of lighter fluid). Jim ambled over to say goodbye. When I mentioned we had a 2½ hour drive back to Anchorage, he said 3 hours wasn’t a long time for Alaskans. He’d made that drive many times when his kids were little just to take them to McDonald’s. I asked if he ever got burned out, living here. He gave a long pause, turning his chin up, letting the question sink in before constructing an answer. “Burned out? Huh. I don’t know. I guess like when I was pulling green chain in the saw mill. I was pretty tired by the end of the day. But that’s how we sleep so good in Alaska.”

He didn’t get it. In the lower 48, we rush, scramble, and hurry trying to outrun time. At the end, we’re burned out. In Alaska, they don’t know what burned out means. They do understand that time can’t be controlled or beaten. Rather, it is observed and appreciated. I hoped to bring a little of that perspective to clinic on Monday morning.

My recommendation to you if want to sleep better, with fewer nightmares, if you want to reduce your risk for burn out, then go to Alaska (or Montana, or Wyoming, or Idaho, or your backyard). Like Thoreau, we can still learn a lot about life from nature. This is not medical advice, it’s life advice.

Some people have nightmares of giant rats attacking from their basements, others encounter monsters from a Stephen King novel. My nightmares are of clinic where time is the beast pursuing me. In my nightmares, I’m running late and can’t get to my next patient, or I’m trapped somehow and unable to get to clinic at all.

liseykina/thinkstockphotos

Time demands that I provide patients access quickly, start clinic on time, double my speed to make up for add-ins, or worse, late patients. Time is a constant, relentless monster, one that has apparently infiltrated my subconscious. Yet, time is relative.

Over Memorial Day weekend, my wife and I flew from San Diego to Alaska. Somewhere between those places time transforms – early summer in San Diego becomes early spring in Alaska.

When we landed, daffodils were in bloom, buds on the alders were just arriving, and the sun struggled to warm the air to 50 degrees. The daytime defied gravity: it was daylight by 4 a.m. and still so after 11 p.m. We were the first visitors this season in our little cabin near Seward.

“Your hot water might take a bit to get hot,” our host, Jim, informed us. He wore a thick flannel shirt and Carhartt workman trousers. He leaned against the cabin’s door frame with one hand at the top and the other hanging from the weight of a DeWalt drill at his side. “I made these cabins myself,” he informed. I was anxious to move on, to unpack and start exploring, but every time I tried to break away from his conversation, he extended it. He shared how a cow and calf (that’s moose talk) had come through earlier that morning. Then he told us about working in the timber industry, starting by “pulling green chain” and working his way up to being the keeper of the saws. While he talked, I watched a raven drop down from the tall Sitka spruce to a branch just across from where we parked our car. Just behind Jim, the raven was not only watching, but also listening in on our conversation. Jim pointed, “That bit of snow over there was all that was left from the 12-foot-high snow earlier this year. It was an easy winter.” He then advised we should start our trip with a visit to Exit Glacier. It was reachable by road and an easy hike.

Leamus/iStock/Getty Images

Staying upright on the steep trail to the glacier’s Harding Icefield concentrates the mind. Looking down and across the glacial outwash, I imagined how the ice once thousands of feet above my head carved a valley from rock. Ice compacted so completely and so deep that only blue light escapes. Indeed, a glacier is just a pile of unmelted snow, thousands of years in the making. The Kenai fjords, deep enough that humpback whales swim there, were carved from granite – at glacial speed. Some of the rocks there contain fossils all the way from the tropics. They were transported by the Pacific tectonic plate that has rotated counterclockwise from the equator to Alaska over millions of years – at tectonic speed. Life here has a way of sharpening your focus, allowing you to see perspective as exists in nature. Alaska is so old that an ob.gyn. could have seen his or her first patient here – a mother with a stillborn child – at the Upward Sun River, 11,500 years ago, where in 2013, the fossil remains of a late-term fetus dating back to that time was discovered. It is indeed relative.

After a long hike, a crispy, hot halibut sandwich, we made it back to our cabin. There was no WiFi or reliable cell service, no TV, no Netflix. We read in bed by daylight. I slept soundly, despite the bright light. No nightmares. No monsters.

The next morning, as I sipped my steaming coffee on our porch, the raven didn’t waste much time to stop by. He paused before coming nearly eye to eye on the roof of the firewood shed in front of me. He looked me up and down and cackled. Not a cawh, not warning me of my intrusion, but rather a vocalization. He just wanted to strike up a conversation with the first guest of the season. He had nothing but time.

On our last night, I lit a fire with wood Jim had cut for us (with help from lots of lighter fluid). Jim ambled over to say goodbye. When I mentioned we had a 2½ hour drive back to Anchorage, he said 3 hours wasn’t a long time for Alaskans. He’d made that drive many times when his kids were little just to take them to McDonald’s. I asked if he ever got burned out, living here. He gave a long pause, turning his chin up, letting the question sink in before constructing an answer. “Burned out? Huh. I don’t know. I guess like when I was pulling green chain in the saw mill. I was pretty tired by the end of the day. But that’s how we sleep so good in Alaska.”

He didn’t get it. In the lower 48, we rush, scramble, and hurry trying to outrun time. At the end, we’re burned out. In Alaska, they don’t know what burned out means. They do understand that time can’t be controlled or beaten. Rather, it is observed and appreciated. I hoped to bring a little of that perspective to clinic on Monday morning.

My recommendation to you if want to sleep better, with fewer nightmares, if you want to reduce your risk for burn out, then go to Alaska (or Montana, or Wyoming, or Idaho, or your backyard). Like Thoreau, we can still learn a lot about life from nature. This is not medical advice, it’s life advice.

Some people have nightmares of giant rats attacking from their basements, others encounter monsters from a Stephen King novel. My nightmares are of clinic where time is the beast pursuing me. In my nightmares, I’m running late and can’t get to my next patient, or I’m trapped somehow and unable to get to clinic at all.

liseykina/thinkstockphotos

Time demands that I provide patients access quickly, start clinic on time, double my speed to make up for add-ins, or worse, late patients. Time is a constant, relentless monster, one that has apparently infiltrated my subconscious. Yet, time is relative.

Over Memorial Day weekend, my wife and I flew from San Diego to Alaska. Somewhere between those places time transforms – early summer in San Diego becomes early spring in Alaska.

When we landed, daffodils were in bloom, buds on the alders were just arriving, and the sun struggled to warm the air to 50 degrees. The daytime defied gravity: it was daylight by 4 a.m. and still so after 11 p.m. We were the first visitors this season in our little cabin near Seward.

“Your hot water might take a bit to get hot,” our host, Jim, informed us. He wore a thick flannel shirt and Carhartt workman trousers. He leaned against the cabin’s door frame with one hand at the top and the other hanging from the weight of a DeWalt drill at his side. “I made these cabins myself,” he informed. I was anxious to move on, to unpack and start exploring, but every time I tried to break away from his conversation, he extended it. He shared how a cow and calf (that’s moose talk) had come through earlier that morning. Then he told us about working in the timber industry, starting by “pulling green chain” and working his way up to being the keeper of the saws. While he talked, I watched a raven drop down from the tall Sitka spruce to a branch just across from where we parked our car. Just behind Jim, the raven was not only watching, but also listening in on our conversation. Jim pointed, “That bit of snow over there was all that was left from the 12-foot-high snow earlier this year. It was an easy winter.” He then advised we should start our trip with a visit to Exit Glacier. It was reachable by road and an easy hike.

Leamus/iStock/Getty Images

Staying upright on the steep trail to the glacier’s Harding Icefield concentrates the mind. Looking down and across the glacial outwash, I imagined how the ice once thousands of feet above my head carved a valley from rock. Ice compacted so completely and so deep that only blue light escapes. Indeed, a glacier is just a pile of unmelted snow, thousands of years in the making. The Kenai fjords, deep enough that humpback whales swim there, were carved from granite – at glacial speed. Some of the rocks there contain fossils all the way from the tropics. They were transported by the Pacific tectonic plate that has rotated counterclockwise from the equator to Alaska over millions of years – at tectonic speed. Life here has a way of sharpening your focus, allowing you to see perspective as exists in nature. Alaska is so old that an ob.gyn. could have seen his or her first patient here – a mother with a stillborn child – at the Upward Sun River, 11,500 years ago, where in 2013, the fossil remains of a late-term fetus dating back to that time was discovered. It is indeed relative.

After a long hike, a crispy, hot halibut sandwich, we made it back to our cabin. There was no WiFi or reliable cell service, no TV, no Netflix. We read in bed by daylight. I slept soundly, despite the bright light. No nightmares. No monsters.

The next morning, as I sipped my steaming coffee on our porch, the raven didn’t waste much time to stop by. He paused before coming nearly eye to eye on the roof of the firewood shed in front of me. He looked me up and down and cackled. Not a cawh, not warning me of my intrusion, but rather a vocalization. He just wanted to strike up a conversation with the first guest of the season. He had nothing but time.

On our last night, I lit a fire with wood Jim had cut for us (with help from lots of lighter fluid). Jim ambled over to say goodbye. When I mentioned we had a 2½ hour drive back to Anchorage, he said 3 hours wasn’t a long time for Alaskans. He’d made that drive many times when his kids were little just to take them to McDonald’s. I asked if he ever got burned out, living here. He gave a long pause, turning his chin up, letting the question sink in before constructing an answer. “Burned out? Huh. I don’t know. I guess like when I was pulling green chain in the saw mill. I was pretty tired by the end of the day. But that’s how we sleep so good in Alaska.”

He didn’t get it. In the lower 48, we rush, scramble, and hurry trying to outrun time. At the end, we’re burned out. In Alaska, they don’t know what burned out means. They do understand that time can’t be controlled or beaten. Rather, it is observed and appreciated. I hoped to bring a little of that perspective to clinic on Monday morning.

My recommendation to you if want to sleep better, with fewer nightmares, if you want to reduce your risk for burn out, then go to Alaska (or Montana, or Wyoming, or Idaho, or your backyard). Like Thoreau, we can still learn a lot about life from nature. This is not medical advice, it’s life advice.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.

Case

A 24-year-old man in cardiac arrest was brought to the ED via emergency medical services (EMS). Unfortunately, resuscitation efforts were unsuccessful. Little was known about the patient, but the emergency physician was informed that the patient had ingested sodium azide (NaN₃), which he had ordered online. The patient collapsed shortly after ingesting the sodium azide, approximately the same time police officers arrived at the patient’s home.

No specific details were known about the patient’s ingestion. Upon learning of the exposure to sodium azide, a member of the ED staff contacted the local poison control center for information on the proper course of action to ensure staff safety and limit exposure. Shortly thereafter, several of emergency medical technicians and police officers, who had responded to the emergency assistance call for this patient, presented to the ED with concerns of exposure.

What is sodium azide?

Sodium azide is a colorless, odorless crystalline water-soluble solid that has a pK of 4.8.¹ When sodium azide is dissolved in an acid, it liberates hydrazoic acid (HN₃), which has a pungent odor, high vapor pressure (484 mm Hg), and a relatively low-boiling point of 37°C (98°F).²

The most common industrial use of sodium azide is as a propellant in air bags. In this capacity, sodium azide rapidly decomposes to nitrogen gas when it reaches a temperature of 300°C (572°F), causing rapid expansion of the air bag. In addition to air bags, sodium azide is used in research laboratories as a preservative and in agriculture as a pesticide. The main nontoxicological concern with all azide agents is the potential for explosion when they react with metals, such as lead, copper, silver, and mercury, to form metal azides that are sensitive to shock.³ An example of the explosive nature of these azides was demonstrated in a report wherein diluted sodium azide was poured down a drain, causing an explosion as a worker was fixing the pipe.⁴

In addition to industrial and commercial use, sodium azide is occasionally used in suicide attempts because it is rapidly fatal, has no specific antidote, and can be purchased online.³

What is the toxicity of sodium azide?

The lethal dose for both oral and dermal exposure to sodium azide is approximately 10 to 20 mg/kg.^3,5 Therefore, ingestion of 700 mg of sodium azide, a volume approximately the size of a penny, is likely to be fatal.³

Sodium azide is primarily a mitochondrial toxin, which binds the electron transport chain, inhibiting oxidative phosphorylation. The resulting reduction in adenosine triphosphate (ATP) production, even in the presence of oxygen, results in metabolic failure.⁶ This mechanism of action is similar to that of cyanide, although sodium azide causes more pronounced vasodilation due to the in vivo conversion of some azide to the vasodilator nitric oxide.⁷ Some reports suggest that azide lethality is due to enhanced excitatory transmission from nitric oxide in the central nervous system.⁸

What are the clinical manifestations of azide poisoning, and what is the treatment?

The early clinical findings of a patient with azide poisoning include hypotension, dizziness, headache, nausea, vomiting, palpitations, tachycardia, dyspnea, and restlessness. Inhalation of hydrazoic acid can also produce wheezing and coughing. The most common effect is hypotension, which can occur within 1 minute of exposure. Following depletion of cellular ATP, anaerobic glycolysis generates lactate and produces acidemia. More severe findings of azide poisoning include seizures, cardiac arrhythmia, loss of consciousness, pulmonary edema, and cardiopulmonary failure.³

Currently, there is no specific antidote for azide poisoning, and treatment mainly consists of supportive care. Cyanide antidote treatments are generally ineffective in reducing azide-related death in animal models.^3,8Early aggressive supportive care can improve survival rates.⁹ Some authors suggest that administration of oral activated charcoal, orogastric lavage, hemodialysis, and plasma exchange reduce azide concentrations, while others believe these treatments have little effect.^3,9 More research is needed to identify effective therapeutic measures and to control for dose, time, and patient population.

What are the safety concerns for emergency medical technicians and hospital staff following exposure to sodium azide?

The most probable routes of exposure for prehospital and hospital staff include dermal contact with sodium azide or inhalation of gaseous hydrazoic acid; inhalational exposure is most concerning.¹ In one case, hospital-staff members developed headaches, light-headedness, and nausea while treating a patient for azide poisoning; however, staff exposure was not confirmed and no sequelae were evident.¹⁰

More objectively, workers at an azide plant exposed to azide concentrations above the occupational exposure limit developed headaches, hypotension, and palpitations.¹¹ Another study found no evidence of kidney, heart, or liver damage after patients were given sodium azide for more than a year during a clinical trial.¹² Not unexpectedly, there is little risk of exposure when proper safety precautions are taken.

Emergency response personnel should carefully inspect the scene for the presence of any sodium azide powder, and should also question bystanders and family members to determine if anyone performed mouth-to-mouth resuscitation on the patient. Standard universal precautions, along with attentiveness to one’s surroundings, should be sufficient to prevent dermal exposure. If small amounts of sodium azide residue are found on the patient, his or her clothes should be cautiously removed and placed in a plastic bag to prevent dispersion of particles. If large quantities of sodium azide are present on a patient, the hazardous materials response team should be called, in accordance with institutional and regional protocols. To avoid explosion, every attempt should be made to prevent azide salt (eg, from emesis) from contact with any metal surfaces (eg, oxygen tanks, metal stretcher).¹³Vomit from patients who have ingested sodium azide can cause liberation of hydrazoic acid, which can escape through the esophagus. A pungent ambient odor may provide a warning, which is particularly concerning in a confined space such as an ambulance. As a precaution, EMS personnel should open windows and maximize ventilation. After the call, EMS and hospital personnel should thoroughly wash their hands with soap and water, and change their uniform if they believe it has been contaminated. There is no risk of delayed exposure following exposure to hydrazoic acid.

During autopsy, medical examiners must exercise caution due to the potential for liberation of hydrazoic acids from the stomach.¹⁴Unless it is absolutely necessary, the medical examiner should avoid opening the stomach. If this is unavoidable, the autopsy should occur in a well-ventilated setting with the examiner wearing a supplied air respirator to limit exposure in a high-risk scenario.

Case Conclusion

None of the exposed first responders experienced dizziness, light-headedness, or irritation, and after a period of observation in the ED, they were discharged home without further sequelae. All hospital staff involved in the patient’s care, including those who performed cardiopulmonary resuscitation on the patient and cleaned his room, were advised to use protective equipment when handling the patient and bodily secretions. None of the health care workers developed abnormal clinical findings. Given the hazard in conducting a full postmortem examination, the medical examiner opted to send blood, bile, urine, and vitreous humor out for analysis, but did not conduct a full postmortem examination. Notably, the stomach was not opened, and its contents were not exposed.