SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.

The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).

Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.

SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.

The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).

Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.

SAN DIEGO – Compelling findings in a genetically engineered mouse model of multiple sclerosis identify mechanisms of how adolescence and gut dysbiosis contribute to the risk of MS. In addition, disparities in gut microbiome species could explain why some people are at higher risk for developing multiple sclerosis, while others seem to enjoy a protective effect against development of this and other autoimmune diseases.

The hope is that these findings could pave the way for clinicians to potentially prevent development of multiple sclerosis in people at higher risk, perhaps through altering the gut flora and probiotic therapy, Suhayl Dhib-Jalbut, MD, said in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Dr. Dhib-Jalbut and his team discovered these findings using humanized transgenic mice – in other words, mice containing risk genes for triggering disease transferred from a patient with multiple sclerosis. The mice were more likely to develop MS-like disease at certain ages and in the presence of an altered gut microbiome or gut dysbiosis (Proc Natl Acad Sci U S A. 2017 Oct 31;114[44]:E9318-27).

Dr. Dhib-Jalbut is past president of ACTRIMS and is professor and chairman of the departments of neurology at Rutgers–Robert Wood Johnson Medical School, New Brunswick, N.J., and New Jersey Medical School, Newark. He has received research grants from Biogen and Teva, and is a consultant for Genzyme, Teva, Celgene, and, Mallinckrodt.

LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.

Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.

The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.

Michele G. Sullivan/Frontline Medical News

At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).

Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).

The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).

Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.

Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).

The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.

The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.

SOURCE: Wang Y et al. ISC 2018, abstract LB8

LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.

Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.

The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.

Michele G. Sullivan/Frontline Medical News

At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).

Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).

The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).

Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.

Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).

The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.

The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.

SOURCE: Wang Y et al. ISC 2018, abstract LB8

LOS ANGELES – In patients who had experienced a minor stroke or a transient ischemic attack with a moderate to high risk of stroke, the combination of ticagrelor and aspirin reduced the 90-day incidence of high on-treatment platelet reactivity, according to results from the PRINCE trial.

Although the combination outperformed clopidogrel (Plavix) plus aspirin, ticagrelor (Brilinta) was associated with higher bleeding risk.

The researchers also saw a trend toward a reduction in strokes that did not reach statistical significance, but the trial was halted following an interim analysis showing that the high on-treatment platelet reactivity (HOPR) endpoint, defined as P2Y12 reaction unit (PRU) greater than 208, showed a statistically significant difference. “To prove the clinical benefit, we will need a larger sample size,” study first author and presenter Yilong Wang, MD, PhD, of Beijing Tiantan Hospital, Capital Medical University, said in an interview at the International Stroke Conference, sponsored by the American Heart Association.

Michele G. Sullivan/Frontline Medical News

At 90 days, the mean PRU value was 175.44 in the Clop group, compared with 69.24 in the Tica group. Overall, 27.7% of the Clop group experienced HOPR in the first 7 days, compared with 3.9% of the Tica group. At 90 days, 29.7% of the Clop group had experienced HOPR, compared with 12.5% of the Tica group (odds ratio, 0.33; 95% confidence interval, 0.21-0.51; P less than .001).

Ticagrelor was associated with greater benefit among those with impaired ability to metabolize clopidogrel. Among poor metabolizers, HOPR occurred in 10.5% in the Tica group and 42.4% of the Clop group (OR, 0.16; 95% CI, 0.05-0.56; P = .004). A similar favorable effect was seen in intermediate metabolizers in the Tica group (OR, 0.24; 95% CI, 0.12-0.49; P less than .001).

The 90-day stroke rate was no different between the Tica and Clop groups (6.3% vs. 8.8%, respectively; P = .20).

Minimal bleeding was higher in the Tica group (19.0% vs. 10.6%; hazard ratio, 1.86; P = .003), as was any bleeding (22.3% vs. 14.2%; HR, 1.65; P = .007). There were three deaths in the Tica group and two in the Clop group.

Dyspnea was the most common cause of drug discontinuation, and occurred in 4.2% of patients taking ticagrelor but none of the patients taking clopidogrel (P = .0001).

The researchers hope to demonstrate the clinical benefits of the combination in the upcoming PRINCE 2 trial. The results will have an important impact because CYP2C19 loss of function alleles are more common in Asian population. “It’s a very big problem for us,” Dr. Wang said.

The study was funded by the National Natural Science Foundation of China, the Beijing Institute for Brain, and the Beijing Municipal Science & Technology Commission of Cerebral Vascular Disease. AstraZeneca provided study drugs. Dr. Wang reported having no financial disclosures.

SOURCE: Wang Y et al. ISC 2018, abstract LB8

Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.

For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.

AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.

rfranki@frontlinemedcom.com

Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.

For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.

AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.

rfranki@frontlinemedcom.com

Increases in hepatitis C–related inpatient stays for baby boomers from 2005 to 2014 far outpaced those of older adults, while younger adults saw their admissions drop over that period, according to the Agency for Healthcare Research and Quality.

For the baby boomers (adults aged 52-72 years), the rate of inpatient stays involving hepatitis C with or without hepatitis B, HIV, or alcoholic liver disease rose from 300.7 per 100,000 population in 2005 to 503.1 per 100,000 in 2014 – an increase of over 67%. For patients aged 73 years and older, that rate went from 104.4 in 2005 to 117.1 in 2014, which translates to a 12% increase, and for patients aged 18-51 years, it dropped 15%, from 182.5 to 155.4, the AHRQ said in a statistical brief.

AGA offers tools to help you become more efficient, understand quality standards, and improve the process of care for your hepatitis C patients.

rfranki@frontlinemedcom.com

LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.

The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.

But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Campbell B et al. ISC 2018, abstract LB2.

LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.

The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.

But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Campbell B et al. ISC 2018, abstract LB2.

LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.

The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, Bruce C. Campbell, MBBS, PhD, said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Tenecteplase is a genetically-modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half life and allows for bolus administration, unlike alteplase, which needs continuous infusion (CNS Drugs. 2015 Oct;29[10]:811-8). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.

But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

SOURCE: Campbell B et al. ISC 2018, abstract LB2.

The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.

Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).

The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.

Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.

Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”

The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.

Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).

The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.

Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.

Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”

The results are in: 93% of soldiers, retirees, and family members report very high overall satisfaction with their experience at Army medical treatment facilities.

Survey responses were for the DoD’s 2017 Joint Outpatient Experience Survey (JOES), which also asked about ease of access to Army providers (83% positive response) and overall experience with Army pharmacies (78% positive).

The results showed an increase in satisfaction of about 2% for those 3 questions compared with the results of 2016, the first time the Army participated in the survey, according to Melissa Gliner, senior health policy analyst with the Office of the Army Surgeon General, in an article for Defense.gov. The survey goes to about 10% of patients who have visited a military health facility.

Besides sharing the survey results with the facilities, Gliner advises them on how to improve the patient experience. For instance, she looks at civilian treatment facilities to see what works. One insight she culled was that it helps to have staff members circulate in the waiting area to chat with patients so they do not feel they are being ignored. Another was that facilities should retrain scheduling clerks to set up appointments without making the patient call back.

Gliner says the U.S. Army Medical Command also is working on a website that will help military health facilities share their ideas and “further elevate patient experience and survey scores.”

Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.

Table of Contents

• Mohs Micrographic Surgery in the VHA
• A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
• Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
• Why Am I Being Treated Like a Female Breast Cancer Patient?
• Breast Cancer Tumor Board
• Advances in CAR T-Cell Therapies

Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.

Table of Contents

• Mohs Micrographic Surgery in the VHA
• A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
• Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
• Why Am I Being Treated Like a Female Breast Cancer Patient?
• Breast Cancer Tumor Board
• Advances in CAR T-Cell Therapies

Click here to access the Best Practices in Hematology and Oncology 2018 Digital Edition.

Table of Contents

• Mohs Micrographic Surgery in the VHA
• A National WestlawNext Database Analysis of Malpractice Litigation in Radiation Oncology
• Barriers and Facilitators to the Use of Genomic-Based Targeted Therapy in the VA: Qualitative Findings
• Why Am I Being Treated Like a Female Breast Cancer Patient?
• Breast Cancer Tumor Board
• Advances in CAR T-Cell Therapies

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

Photo by Rhoda Baer

Interim results from randomized trials may be misleading at times, according to research published in JAMA.

Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.

“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.

To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.

For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.

Findings

Interim results were reported in 613 of 1267 screened publications.

Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.

Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.

Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.

The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.

In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.

For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”

In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”

Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.

To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)

“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.

Photo by Rhoda Baer

Interim results from randomized trials may be misleading at times, according to research published in JAMA.

Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.

“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.

To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.

For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.

Findings

Interim results were reported in 613 of 1267 screened publications.

Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.

Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.

Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.

The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.

In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.

For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”

In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”

Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.

To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)

“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.

Photo by Rhoda Baer

Interim results from randomized trials may be misleading at times, according to research published in JAMA.

Researchers compared interim and final publications on randomized trials and found that, 21% of the time, results changed significantly.

“Changes between interim and final publication matter because clinicians and the public could have been misled about whether an intervention was beneficial, harmful, or ineffective,” said study author Lisa Schwartz, MD, of Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

She and her colleagues searched PubMed for randomized trials from 2006 to 2015 with “interim,” “not mature,” or “immature” in the title or abstract.

To identify final publications, they searched PubMed, ClinicalTrials.gov, and Web of Science through 2016. The team emailed authors of interim reports when no final publication was identified.

For interim and final publications reporting the same efficacy and or safety outcome, the researchers compared trial characteristics and prominence. They also categorized abstract conclusions (not different, beneficial, or harmful) and compared changes between interim and final publications.

Findings

Interim results were reported in 613 of 1267 screened publications.

Of those publications, 72% reported on trials stopped early (for benefit, harm, futility, or other problems). The remaining 171 ongoing trials (mostly in oncology, surgery, or cardiology) reported interim efficacy or safety results.

Forty-one percent of the publications stated that the interim analysis was specified in the protocol, but half provided no reason for the interim publication.

Final results were published for 98 of the 160 trials (61%) that were more than 1 year beyond the completion date.

The researchers compared 73 interim and final publications reporting the same efficacy or safety outcome. And they found that interim and final publications had similar prominence.

In most cases (79%), the abstract conclusions did not change from the interim publication to the final publication. However, for 21% of trials, there were significant changes.

For 4 trials, the conclusions changed from “no difference” between randomized to treatments to the study treatment being “beneficial.” In 3 trials, the conclusions changed from “not different” to “harmful or possibly harmful.”

In 6 trials, the conclusions changed from “beneficial” to “not different.” One trial changed from “beneficial” to “harmful,” and another changed from “inconclusive” to “noninferior.”

Dr Schwartz and her colleagues concluded that while most interim and final publications reached similar conclusions, frequent non-publication of final results can lead to confusion or unfounded assumptions with true treatment effects remaining unknown.

To safeguard against any such confusion, the researchers recommended routinely adding the word “interim” in the title and justifying the reason in the publication. (Many interim publications reported analyses without any justification.)

“Most importantly, journals, authors, and funders should commit to making final results accessible by linking interim publications to final reports whenever available,” said study author Steven Woloshin, MD, of Dartmouth Institute for Health Policy and Clinical Practice.

IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

IN THIS ARTICLE

• Diagnosis
• Management
• Outcome for the case patient

An otherwise healthy 9-year-old boy is brought to the emergency department (ED) by his father for evaluation of severe pain, blurry vision, and four hours of tearing in his right eye. The patient was in school when he experienced sudden-onset irritation and scratching pain that caused him to rub his eye. He says it “feels like there is something in my eye,” but he denies any known substance or foreign body. He has no medical or surgical history, does not wear contact lenses or eyeglasses, and denies loss of vision. There is no history of recent illness or travel.

On evaluation, the patient is in no acute distress but is holding his right eye closed due to foreign-body sensation and increased photosensitivity and tearing. There is no obvious erythema or swelling in the upper or lower eyelids bilaterally. A visual acuity test with a Snellen eye chart shows 20/20 vision in the left eye and 20/50 in the right, secondary to pain, photophobia, and excessive tearing. The patient’s right sclera is significantly injected. Intraocular pressure, measured with a tonometer, is 12 to 14 mm Hg. A fluorescein stain of the eye yields no significant findings. The globe is intact.

At first glance, a slit-lamp exam shows no obvious signs of a foreign body. But much higher magnification reveals substantial conjunctival injection and numerous intracorneal linear foreign bodies in the right eye (see Figure 1 for example [not the case patient]). The anterior chamber shows no inflammatory reaction, and findings in the posterior segment are unremarkable.

The initial diagnosis is simple conjunctivitis—but closer examination reveals multiple fine, barbed hairs embedded in the patient’s right cornea. Upon further questioning, the patient reports that prior to symptom onset, he had been holding the classroom pet, a Chilean Rose tarantula, in the palm of his hands.

DISCUSSION

Foreign body injury is a common cause of ocular pain and corneal damage, which can lead to challenging complications. Ophthalmic emergencies account for 2% of ED visits in the US annually and are a major cause of visual impairment.¹ But when a painful eye is the chief complaint, contact with insects, plants, or spiders is rarely included in the differential. Tarantulas are popular classroom and household pets, however, and ocular injury should be suspected in anyone who has been holding a tarantula prior to onset of pain.

Ophthalmia nodosa

Tarantulas are one of the most common arachnids known to cause ophthalmia nodosa—a granulomatous reaction of the conjunctiva or cornea to an implanted plant, insect, or spider hair that typically manifests with photophobia, irritation, and chemosis.^2,3 Tarantulas, when scared or defending their eggs, shoot urticating setae at the threat—a defensive mechanism largely unknown to parents, tarantula owners, and medical professionals.

Urticating setae are found in roughly 90% of tarantula species throughout tropical and subtropical regions.⁴ Depending on the species, setae can be located on the distal prolateral surface of the palpal femur or the dorsum of the abdomen. They can be released when the tarantula scratches its legs against the abdominal urticating setae patch or scratches the palps against the chelicerae (appendages in front of the mouth), or when direct exterior contact is made with the abdominal setae.⁴

There are six types of urticating hairs. Each is attached to the spider’s cuticle by either a stalk (which represents the break-off region) or a socket.⁴ Tarantula hairs range in size from 0.1 mm to 0.3 mm and have a sharp, pointed head and numerous barbs, which help embed them in the target.⁵ They are long and thin, to facilitate deep tissue penetration, and can enter the eyes, lungs, or other body parts (see Figure 2).

Diagnosis and management

Ophthalmic emergencies can affect the visual system and, if left untreated, can lead to permanent vision loss. Affected patients require immediate medical attention and should be referred to an ophthalmologist for follow-up care.

Diagnosis. A thorough history and physical exam are of utmost importance; tiny setae can be easily overlooked if the examiner is not diligent, and the similar symptomatology can lead to misdiagnosis as simple conjunctivitis.³ A visual acuity test and slit-lamp exam are useful for confirmation.

Treatment. Once the diagnosis is confirmed, treatment should consist of mild topical antibiotics and steroids to effectively control infection and inflammation. While topical steroids may be appropriate, local adverse events associated with their use (eg, glaucoma, cataracts) can be problematic. Gentle eye irrigation has been noted by some researchers as contraindicated, while others find it useful to flush out some of the hairs.^5,8,9

Most of the visible protruding tarantula hairs can and should be removed under microscopy during slit-lamp exam. Hairs that are buried in the cornea, however, are nearly impossible to remove and pose a threat of further complications, as described. Conservative management with careful observation is therefore recommended. If the patient develops a granuloma, excision—along with a course of systemic steroids and setae removal via vitrectomy—may be needed.⁹

The good news is that, in many cases, deeper hairs are absorbed without complication, making their removal unnecessary.⁵ Factors that encourage leaving the setae untouched include a large number of hairs, deep corneal penetration, lack of patient tolerance for the procedure, and risk for perforation.³

More invasive treatments (eg, laser photocoagulation, intraocular surgery) to remove offending hairs are possible, but literature on the outcome of these interventions is limited. One report to date used argon laser photocoagulation to treat endophthalmitis from vitreous hairs.¹⁰ The laser can fragment the hairs so that they lose their barbed characteristic and cannot penetrate deeper.⁶

Follow-up. Close follow-up is advised, and patients should be educated on the importance of medication compliance and return visits for reevaluation. Given the potential dangers of handling these spiders, tarantula owners should be advised to use protective gloving and goggles.^2,5,8,9

OUTCOME FOR THE CASE PATIENT

The case patient was sent to an ophthalmologist on day 1. Proparacaine was placed in his right eye, and all of the superficial tarantula hairs were removed using 25- and 30-gauge needles with jeweler forceps under slit-lamp microscopy. Most of the hairs were removed from the superior cornea; fewer were found in the paracentral and inferior regions of the cornea. Approximately five hairs in the paracentral area of the cornea were embedded in the midstromal depth and could not be removed. One drop of ciprofloxacin was administered.

The patient was sent home with an eye shield and instructions to use tobramycin/dexamethasone eye drops (qid in his right eye) and avoid rubbing the eye. (The eye shield, though not technically necessary, was deemed beneficial to help the patient avoid touching the eye.) He was scheduled to return to the clinic one week later.

On follow-up, a careful exam performed under microscopy showed that the five tarantula hairs were still embedded, and an additional six hairs were found in the deep stroma. Superficial punctate keratitis—an eye disorder caused by epithelial cell death on the surface of the cornea—was noted, but no anterior chamber cells were seen. The patient was instructed to continue using the eye drops as prescribed until finished, then start using loteprednol (tid) and artificial lubricating tears (every 2 h).

He returned to the clinic every two weeks for a total of 10 visits. At the end of the treatment course, the remaining tarantula hairs were unable to be removed. The patient used tapering doses of topical eye steroids and antibiotic drops secondary to flare-up.

CONCLUSION

Determining the etiology of ophthalmic emergencies is essential to timely and appropriate management. In this case, a recognized but often overlooked cause, tarantula hairs, made the diagnosis more complicated than simple conjunctivitis. When ocular injury is suspected, the provider must obtain an accurate and detailed history along with a thorough physical exam. Since patients must comply with medication regimens to prevent acute and chronic infection, a clear treatment and follow-up plan should be established. With these in place, ophthalmia nodosa caused by urticating setae can be effectively managed.

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
 

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).
 

This is the second part in a series on medication pricing.

In my last column, I looked at the tremendous variation in prices among pharmacies for two psychotropic medications, aripiprazole and modafinil. The cash price variation could be as much as 45 times more from one pharmacy to the next, which I found to be both outrageous and incomprehensible.

To learn more about pharmaceutical pricing, I contacted Doug Hirsch, the cofounder of GoodRx, a firm based in Santa Monica, Calif., that offers deep discounts on some medications. The company sends discount cards to physicians’ offices – call me if you need some, I have many boxes of GoodRx cards – and has a website (www.GoodRx.com) and an app. It advertises that it is about transparency, and if you’ve ever tried the company’s site or app, the service it offers is remarkable and simple to use.

tab1962/Thinkstock

I went back to the enormous cost discrepancy that I had discovered a couple of years ago with Provigil (modafinil). Thirty pills cost just under $35 at Costco, while all other pharmacies were charging close to $1,000. Mr. Hirsch explained, “From what I’ve been told, Costco bases their prices on their acquisition costs and then raises them a certain percent. It’s one way to provide a fair price, but that doesn’t mean they always have the lowest price. They are also the only major pharmacy that lists their drug prices on their website.”

I wanted to know what was in it for the PBMs. Why would Express Scripts be motivated to negotiate a discount in price for cash-paying customers outside of the insurance networks, and how did partnering with GoodRx benefit them? The answer, in part, lies with the fact that the website and app allow patients to comparison shop and go to pharmacies with lower prices. If patients use their insurance, the insurance company is paying less; if they don’t use their insurance because they learned the cash cost is less, then the cost burden has shifted from the insurance company entirely to the patient.

What’s in it for the pharmacies? Why would they be willing to accept less money from a patient bearing a discount card? Mr. Hirsch explained, “Pharmacies want to honor their contracts with PBMs, and the U&C prices are set high to enable negotiation so that they still make some profit. Most people couldn’t afford to pay the high U&C, but they can’t lower them for individual cash-pay customers because that would violate their agreements with PBMs, and Medicare and Medicaid, which is a felony. With the GoodRx price, they still make a profit, and people in drugstores buy other items as well.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016).