Isolated communities in the Canadian province of Newfoundland and Labrador have an “unusual prevalence” of certain hereditary bleeding disorders, a fact attributable to the province’s unique topography and settlement patterns, according to a new study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

The prevalence of hemophilia A in Newfoundland and Labrador (NL) is 2.89 times higher than in the rest of Canada. Deficiencies in Factors V, XI, and XIII are 4.54, 5.44, and 9.22 times more prevalent in NL than mainland Canada, respectively. The study also found more cases than expected of the extremely rare hereditary bleeding disorder, Glanzmann thrombasthenia (n = 4). One case of Bernard-Soulier syndrome was also seen, the investigators reported in Transfusion and Apheresis Science.

“This comparatively high prevalence provides a potential pool of patients for genotype/phenotype research,” wrote Mary-Frances Scully, MD, a hematologist at Memorial University, St. John’s, Nfld., and her associates.

In addition to founding populations of indigenous Innu, Inuit, and Mi’kmaq populations, present-day residents of Canada’s easternmost province trace their lineages to about 28,000 settlers who came from southwest England and southeast Ireland for the area’s rich fisheries, explained Dr. Scully and her coauthors. The overall population density of NL is still very low, at about 1.38 individuals per square kilometer, less than half that of Canada overall and far less than the United States’ 36 per square kilometer.

Overall, the investigators reviewed records for 180 patients with hereditary bleeding disorders who were receiving specialty care in St. John’s. Most (n = 127) had hemophilia A; of these patients, those who had mutation testing primarily had the Val 2016A1 mutation. This was particularly true for patients with mild hemophilia A. More than 73% (83/111 patients) carried this mutation, demonstrating a founder effect, wrote Dr. Scully and her coauthors. The next most common hereditary bleeding disorder was Factor XI deficiency, seen in 29 patients.

Additionally, of the seven patients with Factor XIII deficiency, five were homozygous for the c.691-1 G greater than A mutation.

More males in NL than in global comparator data had Factor V deficiency and Glanzmann thrombasthenia, though Dr. Scully and her colleagues acknowledged that the numbers were low overall.

Coagulation tests performed at the time of diagnosis and before treatment initiation were used, when available, to ascertain the severity of the bleeding disorder. Patients were included whether they were heterozygous or homozygous for hereditary bleeding disorders, so long as their baseline coagulation factor levels were below predetermined cutoff levels.

Comparing the prevalence of all the hereditary bleeding disorders identified in the NL population against mainland Canada and that of four other reference countries – Iran, Ireland, the United Kingdom, and the United States – the increased prevalence rates in NL were highly statistically significant (P less than .0001) for all but the single case of Bernard-Soulier syndrome.

Hemophilia B was the only hereditary bleeding disorder seen less frequently in the NL population than in Canada or the other reference populations.

“These results show that NL’s unique geography and population distribution led to a genetic drift that increased the prevalence of some rare factor deficiencies,” wrote Dr. Scully and her colleagues.

The investigators plan to continue investigating and reporting genotype and phenotype correlations among their patient population; they also invite broader international collaboration into the prevalence of rare hereditary bleeding disorders in isolated populations.

The authors reported having no conflicts of interest and no outside sources of funding.
 

[email protected]

SOURCE: Scully M-F et al. Transfus Apher Sci. 2018 Dec;57(6):713-6.

Isolated communities in the Canadian province of Newfoundland and Labrador have an “unusual prevalence” of certain hereditary bleeding disorders, a fact attributable to the province’s unique topography and settlement patterns, according to a new study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

The prevalence of hemophilia A in Newfoundland and Labrador (NL) is 2.89 times higher than in the rest of Canada. Deficiencies in Factors V, XI, and XIII are 4.54, 5.44, and 9.22 times more prevalent in NL than mainland Canada, respectively. The study also found more cases than expected of the extremely rare hereditary bleeding disorder, Glanzmann thrombasthenia (n = 4). One case of Bernard-Soulier syndrome was also seen, the investigators reported in Transfusion and Apheresis Science.

“This comparatively high prevalence provides a potential pool of patients for genotype/phenotype research,” wrote Mary-Frances Scully, MD, a hematologist at Memorial University, St. John’s, Nfld., and her associates.

In addition to founding populations of indigenous Innu, Inuit, and Mi’kmaq populations, present-day residents of Canada’s easternmost province trace their lineages to about 28,000 settlers who came from southwest England and southeast Ireland for the area’s rich fisheries, explained Dr. Scully and her coauthors. The overall population density of NL is still very low, at about 1.38 individuals per square kilometer, less than half that of Canada overall and far less than the United States’ 36 per square kilometer.

Overall, the investigators reviewed records for 180 patients with hereditary bleeding disorders who were receiving specialty care in St. John’s. Most (n = 127) had hemophilia A; of these patients, those who had mutation testing primarily had the Val 2016A1 mutation. This was particularly true for patients with mild hemophilia A. More than 73% (83/111 patients) carried this mutation, demonstrating a founder effect, wrote Dr. Scully and her coauthors. The next most common hereditary bleeding disorder was Factor XI deficiency, seen in 29 patients.

Additionally, of the seven patients with Factor XIII deficiency, five were homozygous for the c.691-1 G greater than A mutation.

More males in NL than in global comparator data had Factor V deficiency and Glanzmann thrombasthenia, though Dr. Scully and her colleagues acknowledged that the numbers were low overall.

Coagulation tests performed at the time of diagnosis and before treatment initiation were used, when available, to ascertain the severity of the bleeding disorder. Patients were included whether they were heterozygous or homozygous for hereditary bleeding disorders, so long as their baseline coagulation factor levels were below predetermined cutoff levels.

Comparing the prevalence of all the hereditary bleeding disorders identified in the NL population against mainland Canada and that of four other reference countries – Iran, Ireland, the United Kingdom, and the United States – the increased prevalence rates in NL were highly statistically significant (P less than .0001) for all but the single case of Bernard-Soulier syndrome.

Hemophilia B was the only hereditary bleeding disorder seen less frequently in the NL population than in Canada or the other reference populations.

“These results show that NL’s unique geography and population distribution led to a genetic drift that increased the prevalence of some rare factor deficiencies,” wrote Dr. Scully and her colleagues.

The investigators plan to continue investigating and reporting genotype and phenotype correlations among their patient population; they also invite broader international collaboration into the prevalence of rare hereditary bleeding disorders in isolated populations.

The authors reported having no conflicts of interest and no outside sources of funding.
 

[email protected]

SOURCE: Scully M-F et al. Transfus Apher Sci. 2018 Dec;57(6):713-6.

Isolated communities in the Canadian province of Newfoundland and Labrador have an “unusual prevalence” of certain hereditary bleeding disorders, a fact attributable to the province’s unique topography and settlement patterns, according to a new study.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

The prevalence of hemophilia A in Newfoundland and Labrador (NL) is 2.89 times higher than in the rest of Canada. Deficiencies in Factors V, XI, and XIII are 4.54, 5.44, and 9.22 times more prevalent in NL than mainland Canada, respectively. The study also found more cases than expected of the extremely rare hereditary bleeding disorder, Glanzmann thrombasthenia (n = 4). One case of Bernard-Soulier syndrome was also seen, the investigators reported in Transfusion and Apheresis Science.

“This comparatively high prevalence provides a potential pool of patients for genotype/phenotype research,” wrote Mary-Frances Scully, MD, a hematologist at Memorial University, St. John’s, Nfld., and her associates.

In addition to founding populations of indigenous Innu, Inuit, and Mi’kmaq populations, present-day residents of Canada’s easternmost province trace their lineages to about 28,000 settlers who came from southwest England and southeast Ireland for the area’s rich fisheries, explained Dr. Scully and her coauthors. The overall population density of NL is still very low, at about 1.38 individuals per square kilometer, less than half that of Canada overall and far less than the United States’ 36 per square kilometer.

Overall, the investigators reviewed records for 180 patients with hereditary bleeding disorders who were receiving specialty care in St. John’s. Most (n = 127) had hemophilia A; of these patients, those who had mutation testing primarily had the Val 2016A1 mutation. This was particularly true for patients with mild hemophilia A. More than 73% (83/111 patients) carried this mutation, demonstrating a founder effect, wrote Dr. Scully and her coauthors. The next most common hereditary bleeding disorder was Factor XI deficiency, seen in 29 patients.

Additionally, of the seven patients with Factor XIII deficiency, five were homozygous for the c.691-1 G greater than A mutation.

More males in NL than in global comparator data had Factor V deficiency and Glanzmann thrombasthenia, though Dr. Scully and her colleagues acknowledged that the numbers were low overall.

Coagulation tests performed at the time of diagnosis and before treatment initiation were used, when available, to ascertain the severity of the bleeding disorder. Patients were included whether they were heterozygous or homozygous for hereditary bleeding disorders, so long as their baseline coagulation factor levels were below predetermined cutoff levels.

Comparing the prevalence of all the hereditary bleeding disorders identified in the NL population against mainland Canada and that of four other reference countries – Iran, Ireland, the United Kingdom, and the United States – the increased prevalence rates in NL were highly statistically significant (P less than .0001) for all but the single case of Bernard-Soulier syndrome.

Hemophilia B was the only hereditary bleeding disorder seen less frequently in the NL population than in Canada or the other reference populations.

“These results show that NL’s unique geography and population distribution led to a genetic drift that increased the prevalence of some rare factor deficiencies,” wrote Dr. Scully and her colleagues.

The investigators plan to continue investigating and reporting genotype and phenotype correlations among their patient population; they also invite broader international collaboration into the prevalence of rare hereditary bleeding disorders in isolated populations.

The authors reported having no conflicts of interest and no outside sources of funding.
 

[email protected]

SOURCE: Scully M-F et al. Transfus Apher Sci. 2018 Dec;57(6):713-6.

Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.

“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”

Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.

Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.

Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.

This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.

SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.

Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.

“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”

Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.

Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.

Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.

This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.

SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.

Statin use after a diagnosis of hepatocellular carcinoma (HCC) was associated with a reduced risk of all-cause and cancer-specific mortality, according to recent research published in Clinical Gastroenterology and Hepatology.

“Our current findings are biologically plausible since statins inhibit not only cholesterol synthesis but also reduce other important downstream products, including membrane integrity maintenance, cell signaling, protein synthesis, and cell-cycle progression,” wrote Aaron P. Thrift, PhD, of the section of epidemiology and population sciences and department of medicine at Baylor College of Medicine in Houston, and his colleagues. “Not only can statins have a direct impact on cancer cells through inhibition of the mevalonate pathway within the cancer cells, but the reduction of circulating cholesterol levels through hepatic pathways is indeed considered important.”

Dr. Thrift and his colleagues performed a retrospective cohort analysis of data from 15,422 patients with HCC in the VA Central Cancer Registry who were diagnosed between 2002 and 2016 and filled a prescription for statins. The researchers looked at statin prescriptions filled prior to and after diagnosis, following patients from diagnosis up to a 3-month lag period. The statins analyzed included atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin.

Overall, 78.8% of patients died during 26,680 person-years of follow-up and the median survival time was 17.24 months. The researchers found 14.9% of patients (2,293 patients) with HCC filled prescriptions for statins after their cancer diagnosis. The median time to begin statins after diagnosis was 2.37 months, and patients who used statins after diagnosis had a median survival time of 26.38 months compared with 15.67 months for patients who did not use statins after diagnosis. For HCC patients who used statins, there was a decreased risk of all-cause mortality (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95) and cancer-specific mortality (adjusted HR, 0.85; 95% CI, 0.77-0.93), which was consistent for both high-dose and low-dose statins and for lag periods between 0 months and 12 months after diagnosis.

Limitations in the study were the exclusion of any statins filled at non-VA pharmacies, baseline differences in statin users and nonstatin users that could have affected results, potential misclassification of cirrhosis in the registry, and the lack of generalization to other populations due to a veteran-specific patient cohort.

This study was funded by the National Institutes of Health and VA Health Services Research and Development Service Center for Innovations in Quality, Effectiveness, and Safety. The authors report having no conflicts of interest.

SOURCE: Thrift AP et al. Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2018.12.046.

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.

Courtesy NIH

In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.

For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).

Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.

Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.

In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.

“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.

The authors reported receiving funding from a number of pharmaceutical companies.

[email protected]

SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
 

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.

©vchal/Thinkstock

The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.

The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.

The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).

“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.

The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.

[email protected]

SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.

Combined naltrexone and ketamine reduced depressive symptoms in a small group of patients with major depressive disorder (MDD) and alcohol use disorder (AUD), according to Gihyun Yoon, MD, of the department of psychiatry at Yale University, New Haven, Conn., and associates.

A total of five patients with major depressive disorder and comorbid alcohol use disorder were included in the 8-week, open-label pilot study. Patients received a 380-mg dose of naltrexone, followed by weekly doses of 0.5 mg/kg ketamine for 4 weeks. The patients were followed for an additional 4 weeks. The primary outcome was the clinical response, defined as a 50% or higher improvement from baseline in the Montgomery-Åsberg Depression Rating Scale.

After the first ketamine dose, three of the five study participants met the primary outcome, and all five met the outcome after receiving all four doses. Depressive symptoms improved 57%-92% overall. In addition, four of the five patients reported improvement in alcohol craving and consumption; no adverse events were reported.

“Larger randomized clinical trials are needed to better understand whether opiate receptor stimulation contributes to the antidepressant effects of ketamine. If so, then preclinical research will be needed to help us to understand this role for opiates and its implications for future rapid-acting antidepressant treatments,” concluded Dr. Yoon and associates.

Two study authors reported conflicts of interest with numerous companies. All study authors are listed inventors on a patent application by Yale University.

[email protected]

SOURCE: Yoon G et al. JAMA Psychiatry. 2019 Jan 9. doi: 10.1001/jamapsychiatry.2018.3990.

Combined naltrexone and ketamine reduced depressive symptoms in a small group of patients with major depressive disorder (MDD) and alcohol use disorder (AUD), according to Gihyun Yoon, MD, of the department of psychiatry at Yale University, New Haven, Conn., and associates.

A total of five patients with major depressive disorder and comorbid alcohol use disorder were included in the 8-week, open-label pilot study. Patients received a 380-mg dose of naltrexone, followed by weekly doses of 0.5 mg/kg ketamine for 4 weeks. The patients were followed for an additional 4 weeks. The primary outcome was the clinical response, defined as a 50% or higher improvement from baseline in the Montgomery-Åsberg Depression Rating Scale.

After the first ketamine dose, three of the five study participants met the primary outcome, and all five met the outcome after receiving all four doses. Depressive symptoms improved 57%-92% overall. In addition, four of the five patients reported improvement in alcohol craving and consumption; no adverse events were reported.

“Larger randomized clinical trials are needed to better understand whether opiate receptor stimulation contributes to the antidepressant effects of ketamine. If so, then preclinical research will be needed to help us to understand this role for opiates and its implications for future rapid-acting antidepressant treatments,” concluded Dr. Yoon and associates.

Two study authors reported conflicts of interest with numerous companies. All study authors are listed inventors on a patent application by Yale University.

[email protected]

SOURCE: Yoon G et al. JAMA Psychiatry. 2019 Jan 9. doi: 10.1001/jamapsychiatry.2018.3990.

Combined naltrexone and ketamine reduced depressive symptoms in a small group of patients with major depressive disorder (MDD) and alcohol use disorder (AUD), according to Gihyun Yoon, MD, of the department of psychiatry at Yale University, New Haven, Conn., and associates.

A total of five patients with major depressive disorder and comorbid alcohol use disorder were included in the 8-week, open-label pilot study. Patients received a 380-mg dose of naltrexone, followed by weekly doses of 0.5 mg/kg ketamine for 4 weeks. The patients were followed for an additional 4 weeks. The primary outcome was the clinical response, defined as a 50% or higher improvement from baseline in the Montgomery-Åsberg Depression Rating Scale.

After the first ketamine dose, three of the five study participants met the primary outcome, and all five met the outcome after receiving all four doses. Depressive symptoms improved 57%-92% overall. In addition, four of the five patients reported improvement in alcohol craving and consumption; no adverse events were reported.

“Larger randomized clinical trials are needed to better understand whether opiate receptor stimulation contributes to the antidepressant effects of ketamine. If so, then preclinical research will be needed to help us to understand this role for opiates and its implications for future rapid-acting antidepressant treatments,” concluded Dr. Yoon and associates.

Two study authors reported conflicts of interest with numerous companies. All study authors are listed inventors on a patent application by Yale University.

[email protected]

SOURCE: Yoon G et al. JAMA Psychiatry. 2019 Jan 9. doi: 10.1001/jamapsychiatry.2018.3990.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

Patients with ankylosing spondylitis whose baseline C-reactive protein (CRP) levels were more than three times the upper limit of normal were significantly more likely to respond to 12 weeks of etanercept therapy than were patients with normal baseline CRP levels, investigators reported.

In a post hoc study of 867 patients who received etanercept during clinical trials, the adjusted odds of achieving 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) at week 12 were 190% higher when CRP levels were “very high” rather than normal at baseline (odds ratio, 2.9; 95% confidence interval, 1.8-4.7). Very-high baseline CRP levels (more than three times the upper limit of normal) also significantly predicted week-12 ASAS50, a change in Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) greater than 1.1 (clinically important improvement), and an ASDAS-CRP less than 1.3 (inactive disease), while a normalization of very-high CRP levels by 2, 4, or 8 weeks of treatment was a significant predictor of achieving week-12 ASDAS inactive disease. “Patient-reported outcomes were less consistent predictors of response,” Xenofon Baraliakos, MD, of Ruhr University Bochum in Herne, Germany, and his coinvestigators wrote in Seminars in Arthritis and Rheumatism.


While the advent of tumor necrosis factor (TNF) antagonists has greatly improved outcomes in ankylosing spondylitis, symptom ambiguity and a lack of objective response criteria still impede early diagnosis and radiographic interpretation. Elevated baseline CRP predicted clinical response to anti-TNF therapy by patients with ankylosing spondylitis in several prior post hoc studies. To further evaluate this finding, the researchers pooled and analyzed data from four randomized, placebo-controlled trials of etanercept in adults with ankylosing spondylitis. In all, 43% of patients had a normal baseline CRP level, 34% had a level that was elevated but did not exceed three times the upper limit of normal, and 23% had a very-high level.

Age of onset, disease duration, and baseline Bath Ankylosing Spondylitis Functional Index also predicted response to etanercept therapy. After controlling for these covariates, a very-high baseline CRP remained a significant predictor for all four week-12 outcomes. This finding points to the value of aggressive, early treatment to normalize CRP in patients with ankylosing spondylitis, the researchers wrote. “Bending the curve of inflammation in the early disease may alter the long-term trajectory of ankylosing spondylitis, which is an opportunity that may not exist in the later stages.”

Thus, CRP, in addition to patient-reported and clinical outcomes, might be useful to help monitor response to anti-TNF therapy, the investigators wrote. It remains unclear whether elevated CRP levels also predict future treatment response in patients who are currently clinically improved or stable.

Pfizer funded the post hoc analysis and acquired the company that had funded the trials (Wyeth). Dr. Baraliakos reported consultancy and speaker fees from Pfizer, AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Merck, Novartis, Sandoz, and UCB. Two coinvestigators were Pfizer employees. A third coinvestigator was contracted by Pfizer to provide statistical support.

SOURCE: Baraliakos X et al. Semin Arthritis Rheum. 2018 Nov 2. doi: 10.1016/j.semarthrit.2018.10.019.

CHICAGO – The idea behind putting a biodegradable polymer on a drug-eluting coronary stent is that, once the antirestenosis drug elutes and the polymer that held it degrades, the bare-metal stent left behind would trigger fewer long-term episodes of in-stent thrombosis than would stents that retain their polymer coating. But 10-year follow-up from a large trial that matched two second-generation drug-eluting stents, one with a biodegradable polymer and the other with a durable polymer, showed no statistically significant difference between the two for any clinical outcome, including the incidence of in-stent thrombosis, Sebastian Kufner, MD, said at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The potential advantage of a biodegradable polymer “is expected to occur over time,” and hence following patients for 10 or more years should start to show a clear advantage, at least for the endpoint of stent thrombosis, but that didn’t happen. After a median follow-up of 10.6 years, the cumulative rate of definite or probable stent thrombosis was 1.8% among 1,299 patients who received a sirolimus-eluting stent with a biodegradable polymer (Yukon Choice) and 2.5% among 652 patients who received a second-generation everolimus-eluting stent with a durable polymer (Xience), a difference that was not statistically significant, reported Dr. Kufner, a cardiologist at the The German Heart Centre in Munich.

These two stents also produced comparable 10-year outcomes that showed no statistically significant differences for the outcomes of all-cause death, MI, need for target-lesion revascularization, or the combined incidence of all three of these outcomes. In contrast, both of these second-generation stents showed statistically significant improvements in the combined cardiac endpoint, as well as in all-cause death, and definite stent thrombosis compared with the 652 patients who received the first-generation sirolimus-eluting stent Cypher. Concurrently with Dr. Kufner’s report, the results appeared in an article online (Circulation. 2018 Nov 11. doi: 10.1161/CIRCULATIONAHA.118.038065).


Another notable finding from the 10-year follow-up was the poor prognosis these patients faced after their interventions, including the patients who received second-generation drug-eluting stents. The 10-year rate of all cause death was 30% among patients who received Xience stents, 32% among those treated with Yukon Choice stents, and 37% among patients treated with Cypher stents.

“I’m daunted by this 10-year mortality rate even with the best current drug-eluting stents,” said Roxana Mehran, MD, professor of medicine at Icahn School of Medicine at Mount Sinai in New York and a cochair of the session. “I’m depressed about this as an interventionalist. We need to do better, although it might not just be about the revascularization.” The high mortality in these patients after 10 years may also reflect a lack of optimal medical treatment in some, she suggested.

ISAR-TEST-4 received no commercial funding. Dr. Kufner had no disclosures. Dr. Mehran has an ownership interest in Claret Medical and Elixir Medical, has been a consultant or adviser to Abbott Laboratories, Boston Scientific, Bristol-Myers Squibb, Janssen, Roivant Sciences, and Siemens Medical Solutions, and has received research funding from several companies.

[email protected]

SOURCE: Kufner S et al. AHA scientific sessions, Abstract 18630.

CHICAGO – The idea behind putting a biodegradable polymer on a drug-eluting coronary stent is that, once the antirestenosis drug elutes and the polymer that held it degrades, the bare-metal stent left behind would trigger fewer long-term episodes of in-stent thrombosis than would stents that retain their polymer coating. But 10-year follow-up from a large trial that matched two second-generation drug-eluting stents, one with a biodegradable polymer and the other with a durable polymer, showed no statistically significant difference between the two for any clinical outcome, including the incidence of in-stent thrombosis, Sebastian Kufner, MD, said at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The potential advantage of a biodegradable polymer “is expected to occur over time,” and hence following patients for 10 or more years should start to show a clear advantage, at least for the endpoint of stent thrombosis, but that didn’t happen. After a median follow-up of 10.6 years, the cumulative rate of definite or probable stent thrombosis was 1.8% among 1,299 patients who received a sirolimus-eluting stent with a biodegradable polymer (Yukon Choice) and 2.5% among 652 patients who received a second-generation everolimus-eluting stent with a durable polymer (Xience), a difference that was not statistically significant, reported Dr. Kufner, a cardiologist at the The German Heart Centre in Munich.

These two stents also produced comparable 10-year outcomes that showed no statistically significant differences for the outcomes of all-cause death, MI, need for target-lesion revascularization, or the combined incidence of all three of these outcomes. In contrast, both of these second-generation stents showed statistically significant improvements in the combined cardiac endpoint, as well as in all-cause death, and definite stent thrombosis compared with the 652 patients who received the first-generation sirolimus-eluting stent Cypher. Concurrently with Dr. Kufner’s report, the results appeared in an article online (Circulation. 2018 Nov 11. doi: 10.1161/CIRCULATIONAHA.118.038065).


Another notable finding from the 10-year follow-up was the poor prognosis these patients faced after their interventions, including the patients who received second-generation drug-eluting stents. The 10-year rate of all cause death was 30% among patients who received Xience stents, 32% among those treated with Yukon Choice stents, and 37% among patients treated with Cypher stents.

“I’m daunted by this 10-year mortality rate even with the best current drug-eluting stents,” said Roxana Mehran, MD, professor of medicine at Icahn School of Medicine at Mount Sinai in New York and a cochair of the session. “I’m depressed about this as an interventionalist. We need to do better, although it might not just be about the revascularization.” The high mortality in these patients after 10 years may also reflect a lack of optimal medical treatment in some, she suggested.

ISAR-TEST-4 received no commercial funding. Dr. Kufner had no disclosures. Dr. Mehran has an ownership interest in Claret Medical and Elixir Medical, has been a consultant or adviser to Abbott Laboratories, Boston Scientific, Bristol-Myers Squibb, Janssen, Roivant Sciences, and Siemens Medical Solutions, and has received research funding from several companies.

[email protected]

SOURCE: Kufner S et al. AHA scientific sessions, Abstract 18630.

CHICAGO – The idea behind putting a biodegradable polymer on a drug-eluting coronary stent is that, once the antirestenosis drug elutes and the polymer that held it degrades, the bare-metal stent left behind would trigger fewer long-term episodes of in-stent thrombosis than would stents that retain their polymer coating. But 10-year follow-up from a large trial that matched two second-generation drug-eluting stents, one with a biodegradable polymer and the other with a durable polymer, showed no statistically significant difference between the two for any clinical outcome, including the incidence of in-stent thrombosis, Sebastian Kufner, MD, said at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

The potential advantage of a biodegradable polymer “is expected to occur over time,” and hence following patients for 10 or more years should start to show a clear advantage, at least for the endpoint of stent thrombosis, but that didn’t happen. After a median follow-up of 10.6 years, the cumulative rate of definite or probable stent thrombosis was 1.8% among 1,299 patients who received a sirolimus-eluting stent with a biodegradable polymer (Yukon Choice) and 2.5% among 652 patients who received a second-generation everolimus-eluting stent with a durable polymer (Xience), a difference that was not statistically significant, reported Dr. Kufner, a cardiologist at the The German Heart Centre in Munich.

These two stents also produced comparable 10-year outcomes that showed no statistically significant differences for the outcomes of all-cause death, MI, need for target-lesion revascularization, or the combined incidence of all three of these outcomes. In contrast, both of these second-generation stents showed statistically significant improvements in the combined cardiac endpoint, as well as in all-cause death, and definite stent thrombosis compared with the 652 patients who received the first-generation sirolimus-eluting stent Cypher. Concurrently with Dr. Kufner’s report, the results appeared in an article online (Circulation. 2018 Nov 11. doi: 10.1161/CIRCULATIONAHA.118.038065).


Another notable finding from the 10-year follow-up was the poor prognosis these patients faced after their interventions, including the patients who received second-generation drug-eluting stents. The 10-year rate of all cause death was 30% among patients who received Xience stents, 32% among those treated with Yukon Choice stents, and 37% among patients treated with Cypher stents.

“I’m daunted by this 10-year mortality rate even with the best current drug-eluting stents,” said Roxana Mehran, MD, professor of medicine at Icahn School of Medicine at Mount Sinai in New York and a cochair of the session. “I’m depressed about this as an interventionalist. We need to do better, although it might not just be about the revascularization.” The high mortality in these patients after 10 years may also reflect a lack of optimal medical treatment in some, she suggested.

ISAR-TEST-4 received no commercial funding. Dr. Kufner had no disclosures. Dr. Mehran has an ownership interest in Claret Medical and Elixir Medical, has been a consultant or adviser to Abbott Laboratories, Boston Scientific, Bristol-Myers Squibb, Janssen, Roivant Sciences, and Siemens Medical Solutions, and has received research funding from several companies.

[email protected]

SOURCE: Kufner S et al. AHA scientific sessions, Abstract 18630.

The University of Texas MD Anderson Cancer Center, Houston, and Ascentage Pharma of Suzhou, China, recently formed a 5-year strategic alliance to advance the development of novel cancer therapeutics, primarily for leukemia.

The collaboration, led by Hagop Kantarjian, MD, chair of leukemia at MD Anderson, will use Ascentage’s proprietary Protein-Protein Interaction drug discovery technology platform to develop the company’s apoptosis-targeted and tyrosine kinase inhibitor drug candidates.

The drug candidates will be studied as single-agent therapies and in combinations with other approved or investigational therapeutics. The candidates, chosen for their potential to treat acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myeloproliferative neoplasms, and myelofibrosis, include:

• HQP1351, a third-generation BCR-ABL inhibitor that has been shown to be safe and “highly active” in treating patients with chronic- or accelerated-phase CML, with or without the T3151 mutation. Preliminary results of the phase 1 study were presented at the 2018 annual meeting of the American Society of Hematology (Abstract 791).
• APG-1252, a highly potent Bcl-2 family inhibitor, has high binding affinities to Bcl-2, Bcl-xL and Bcl-w. It has achieved tumor regression in small cell lung cancer, colon, breast, and ALL xenografts. A phase 1, dose-escalating study is currently being conducted (NCT03387332).
• APG-2575, a selective Bcl-2 inhibitor, is being studied in a phase 1, multicenter, single-agent trial in patients with B-cell hematologic malignancies, including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, non-Hodgkin lymphomas, and AML (NCT03537482).
• APG-1387, an inhibitor of apoptosis protein, is being studied in solid tumors and hematologic malignancies (NCT03386526). Investigators asserted that combining it with an anti–programmed death 1 antibody would be “a very attractive approach” for cancer therapy. In advanced solid tumors it has been well tolerated with manageable adverse events, according to a study presented at the 2018 annual meeting of the American Society of Clinical Oncology (Abstract 2593).
• APG-115 is an MDM2-p53 inhibitor that, when combined with radiotherapy, has been shown to enhance the antitumor effect in gastric adenocarcinoma, according to a paper published in the Journal of Experimental & Clinical Cancer Research.

“We will be investigating this pipeline of candidate therapies, and we are interested in the novel mechanism of their actions,” Dr. Kantarjian said in a statement.

[email protected]

The University of Texas MD Anderson Cancer Center, Houston, and Ascentage Pharma of Suzhou, China, recently formed a 5-year strategic alliance to advance the development of novel cancer therapeutics, primarily for leukemia.

The collaboration, led by Hagop Kantarjian, MD, chair of leukemia at MD Anderson, will use Ascentage’s proprietary Protein-Protein Interaction drug discovery technology platform to develop the company’s apoptosis-targeted and tyrosine kinase inhibitor drug candidates.

The drug candidates will be studied as single-agent therapies and in combinations with other approved or investigational therapeutics. The candidates, chosen for their potential to treat acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myeloproliferative neoplasms, and myelofibrosis, include:

• HQP1351, a third-generation BCR-ABL inhibitor that has been shown to be safe and “highly active” in treating patients with chronic- or accelerated-phase CML, with or without the T3151 mutation. Preliminary results of the phase 1 study were presented at the 2018 annual meeting of the American Society of Hematology (Abstract 791).
• APG-1252, a highly potent Bcl-2 family inhibitor, has high binding affinities to Bcl-2, Bcl-xL and Bcl-w. It has achieved tumor regression in small cell lung cancer, colon, breast, and ALL xenografts. A phase 1, dose-escalating study is currently being conducted (NCT03387332).
• APG-2575, a selective Bcl-2 inhibitor, is being studied in a phase 1, multicenter, single-agent trial in patients with B-cell hematologic malignancies, including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, non-Hodgkin lymphomas, and AML (NCT03537482).
• APG-1387, an inhibitor of apoptosis protein, is being studied in solid tumors and hematologic malignancies (NCT03386526). Investigators asserted that combining it with an anti–programmed death 1 antibody would be “a very attractive approach” for cancer therapy. In advanced solid tumors it has been well tolerated with manageable adverse events, according to a study presented at the 2018 annual meeting of the American Society of Clinical Oncology (Abstract 2593).
• APG-115 is an MDM2-p53 inhibitor that, when combined with radiotherapy, has been shown to enhance the antitumor effect in gastric adenocarcinoma, according to a paper published in the Journal of Experimental & Clinical Cancer Research.

“We will be investigating this pipeline of candidate therapies, and we are interested in the novel mechanism of their actions,” Dr. Kantarjian said in a statement.

[email protected]

The University of Texas MD Anderson Cancer Center, Houston, and Ascentage Pharma of Suzhou, China, recently formed a 5-year strategic alliance to advance the development of novel cancer therapeutics, primarily for leukemia.

The collaboration, led by Hagop Kantarjian, MD, chair of leukemia at MD Anderson, will use Ascentage’s proprietary Protein-Protein Interaction drug discovery technology platform to develop the company’s apoptosis-targeted and tyrosine kinase inhibitor drug candidates.

The drug candidates will be studied as single-agent therapies and in combinations with other approved or investigational therapeutics. The candidates, chosen for their potential to treat acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), myeloproliferative neoplasms, and myelofibrosis, include:

• HQP1351, a third-generation BCR-ABL inhibitor that has been shown to be safe and “highly active” in treating patients with chronic- or accelerated-phase CML, with or without the T3151 mutation. Preliminary results of the phase 1 study were presented at the 2018 annual meeting of the American Society of Hematology (Abstract 791).
• APG-1252, a highly potent Bcl-2 family inhibitor, has high binding affinities to Bcl-2, Bcl-xL and Bcl-w. It has achieved tumor regression in small cell lung cancer, colon, breast, and ALL xenografts. A phase 1, dose-escalating study is currently being conducted (NCT03387332).
• APG-2575, a selective Bcl-2 inhibitor, is being studied in a phase 1, multicenter, single-agent trial in patients with B-cell hematologic malignancies, including multiple myeloma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, non-Hodgkin lymphomas, and AML (NCT03537482).
• APG-1387, an inhibitor of apoptosis protein, is being studied in solid tumors and hematologic malignancies (NCT03386526). Investigators asserted that combining it with an anti–programmed death 1 antibody would be “a very attractive approach” for cancer therapy. In advanced solid tumors it has been well tolerated with manageable adverse events, according to a study presented at the 2018 annual meeting of the American Society of Clinical Oncology (Abstract 2593).
• APG-115 is an MDM2-p53 inhibitor that, when combined with radiotherapy, has been shown to enhance the antitumor effect in gastric adenocarcinoma, according to a paper published in the Journal of Experimental & Clinical Cancer Research.

“We will be investigating this pipeline of candidate therapies, and we are interested in the novel mechanism of their actions,” Dr. Kantarjian said in a statement.

[email protected]

The Food and Drug Administration has granted breakthrough therapy designation to crizanlizumab, a monthly infusion for the prevention of vasoocclusive crises in patients with sickle cell disease of all genotypes.

The designation allows the treatment to be reviewed on an expedited schedule.

Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.

In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).

The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.

[email protected]

The Food and Drug Administration has granted breakthrough therapy designation to crizanlizumab, a monthly infusion for the prevention of vasoocclusive crises in patients with sickle cell disease of all genotypes.

The designation allows the treatment to be reviewed on an expedited schedule.

Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.

In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).

The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.

[email protected]

The Food and Drug Administration has granted breakthrough therapy designation to crizanlizumab, a monthly infusion for the prevention of vasoocclusive crises in patients with sickle cell disease of all genotypes.

The designation allows the treatment to be reviewed on an expedited schedule.

Crizanlizumab, marketed by Novartis, is a humanized anti–P-selectin monoclonal antibody that has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.

In the phase 2 SUSTAIN trial, crizanlizumab reduced the median annual rate of vasoocclusive crises that resulted in health care visits by about 45%, compared with placebo (1.63 vs. 2.98; P = .010). The drug also increased the percentage of patients who did not experience any vasoocclusive crises, compared with placebo (35.8% vs. 16.9%; P = .010).

The rates of treatment-emergent and serious adverse events was similar in the drug and placebo arms of the trial.

[email protected]

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

Amazon
Apple Podcasts
Google Podcasts
Spotify






 

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

Amazon
Apple Podcasts
Google Podcasts
Spotify






 

In this episode, the inaugural guest on the MDedge Psychcast, Henry A. Nasrallah, MD, returns to lecture on first-episode psychosis from the Psychopharmacology Update meeting in Cincinnati. Dr. Nasrallah is editor in chief of Current Psychiatry and is the Sydney W. Souers Endowed Chair and professor and chairman of the department of neurology and psychiatry and behavioral neuroscience at Saint Louis University.

If you would like to respond to any of Dr. Nasrallah’s comments in this Masterclass, email us at [email protected].

Amazon
Apple Podcasts
Google Podcasts
Spotify