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Updated EULAR/ACR criteria identify more lupus patients
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.
Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.
“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.
In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.
The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.
Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.
Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).
In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).
The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.
The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.
“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Radin M et al. Art
FROM ARTHRITIS CARE & RESEARCH
Americans getting more sunburns
, for reasons that are unclear, Nicole L. Bolick, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
On the plus side, utilization of indoor tanning plunged in the United States during the same period, a statistic worth celebrating as a public health and legislative success, noted Dr. Bolick, who was at the Harvard T.H. Chan School of Public Health, Boston, when she conducted her study and is now at East Carolina University, Greenville, N.C.
More good news: Her analysis of data from 67,471 nationally representative participants in the Centers for Disease Control and Prevention’s National Health Information Survey for the years 2005, 2010, and 2015 also demonstrated that the public’s adoption of several key skin cancer prevention behaviors is on the rise, although she added that rates clearly remain suboptimal.
For example, the proportion of Americans who practice sun avoidance climbed from 31.7% in 2005 to 35.5% in 2010, and 36.8% in 2015 in a multivariate logistic regression analysis adjusted for demographics, alcohol use, location, smoking status, education level, health insurance, and family and personal history of skin cancer.
Similarly, the use of sunscreen always or most of the time when outdoors for more than 1 hour on a warm, sunny day rose from an adjusted 31.5% in 2005 to 33.1% in 2010 and to 34.3% in 2015.
Also, sun protective clothing – long pants, hats, and/or long-sleeved shirts – was utilized always or most of the time by 35.9% of respondents in 2005, 38.4% in 2010, and 37.2% in 2015.
In 2005, 19% of Americans reported having a lifetime history of a physician-performed full body skin examination. The prevalence of this secondary skin cancer prevention measure rose to 22.4% in 2010 and remained the same in 2015.
In the 2005 national survey, 14.1% of respondents reported engaging in indoor tanning within the past year. This figure dropped to 6.2% in 2010 and fell further to 4.1% in 2015.
A history of two or more sunburns within the past year was reported by 18.2% of subjects in 2005, by 21.1% in 2010, and by 19.9% in 2015. It’s unclear whether this unwelcome phenomenon is due to inadequate use of sun protection or increased awareness of the link between sun exposure and skin cancer, with a resultant increase in reporting of sunburns. The influence of climate change is another possible explanation worthy of further study, according to Dr. Bolick.
She reported having no financial conflicts regarding her study, conducted free of commercial support.
, for reasons that are unclear, Nicole L. Bolick, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
On the plus side, utilization of indoor tanning plunged in the United States during the same period, a statistic worth celebrating as a public health and legislative success, noted Dr. Bolick, who was at the Harvard T.H. Chan School of Public Health, Boston, when she conducted her study and is now at East Carolina University, Greenville, N.C.
More good news: Her analysis of data from 67,471 nationally representative participants in the Centers for Disease Control and Prevention’s National Health Information Survey for the years 2005, 2010, and 2015 also demonstrated that the public’s adoption of several key skin cancer prevention behaviors is on the rise, although she added that rates clearly remain suboptimal.
For example, the proportion of Americans who practice sun avoidance climbed from 31.7% in 2005 to 35.5% in 2010, and 36.8% in 2015 in a multivariate logistic regression analysis adjusted for demographics, alcohol use, location, smoking status, education level, health insurance, and family and personal history of skin cancer.
Similarly, the use of sunscreen always or most of the time when outdoors for more than 1 hour on a warm, sunny day rose from an adjusted 31.5% in 2005 to 33.1% in 2010 and to 34.3% in 2015.
Also, sun protective clothing – long pants, hats, and/or long-sleeved shirts – was utilized always or most of the time by 35.9% of respondents in 2005, 38.4% in 2010, and 37.2% in 2015.
In 2005, 19% of Americans reported having a lifetime history of a physician-performed full body skin examination. The prevalence of this secondary skin cancer prevention measure rose to 22.4% in 2010 and remained the same in 2015.
In the 2005 national survey, 14.1% of respondents reported engaging in indoor tanning within the past year. This figure dropped to 6.2% in 2010 and fell further to 4.1% in 2015.
A history of two or more sunburns within the past year was reported by 18.2% of subjects in 2005, by 21.1% in 2010, and by 19.9% in 2015. It’s unclear whether this unwelcome phenomenon is due to inadequate use of sun protection or increased awareness of the link between sun exposure and skin cancer, with a resultant increase in reporting of sunburns. The influence of climate change is another possible explanation worthy of further study, according to Dr. Bolick.
She reported having no financial conflicts regarding her study, conducted free of commercial support.
, for reasons that are unclear, Nicole L. Bolick, MD, reported at the virtual annual meeting of the American Academy of Dermatology.
On the plus side, utilization of indoor tanning plunged in the United States during the same period, a statistic worth celebrating as a public health and legislative success, noted Dr. Bolick, who was at the Harvard T.H. Chan School of Public Health, Boston, when she conducted her study and is now at East Carolina University, Greenville, N.C.
More good news: Her analysis of data from 67,471 nationally representative participants in the Centers for Disease Control and Prevention’s National Health Information Survey for the years 2005, 2010, and 2015 also demonstrated that the public’s adoption of several key skin cancer prevention behaviors is on the rise, although she added that rates clearly remain suboptimal.
For example, the proportion of Americans who practice sun avoidance climbed from 31.7% in 2005 to 35.5% in 2010, and 36.8% in 2015 in a multivariate logistic regression analysis adjusted for demographics, alcohol use, location, smoking status, education level, health insurance, and family and personal history of skin cancer.
Similarly, the use of sunscreen always or most of the time when outdoors for more than 1 hour on a warm, sunny day rose from an adjusted 31.5% in 2005 to 33.1% in 2010 and to 34.3% in 2015.
Also, sun protective clothing – long pants, hats, and/or long-sleeved shirts – was utilized always or most of the time by 35.9% of respondents in 2005, 38.4% in 2010, and 37.2% in 2015.
In 2005, 19% of Americans reported having a lifetime history of a physician-performed full body skin examination. The prevalence of this secondary skin cancer prevention measure rose to 22.4% in 2010 and remained the same in 2015.
In the 2005 national survey, 14.1% of respondents reported engaging in indoor tanning within the past year. This figure dropped to 6.2% in 2010 and fell further to 4.1% in 2015.
A history of two or more sunburns within the past year was reported by 18.2% of subjects in 2005, by 21.1% in 2010, and by 19.9% in 2015. It’s unclear whether this unwelcome phenomenon is due to inadequate use of sun protection or increased awareness of the link between sun exposure and skin cancer, with a resultant increase in reporting of sunburns. The influence of climate change is another possible explanation worthy of further study, according to Dr. Bolick.
She reported having no financial conflicts regarding her study, conducted free of commercial support.
FROM AAD 20
SPK-8011 AAV-mediated hemophilia A therapy shows stability, durability
SPK-8011, an investigational adeno-associated virus (AAV)–mediated gene therapy for hemophilia A, provides stable and durable factor VIII expression with no major safety concerns, according to findings at least 2 years after a single treatment in patients from a phase 1/2 trial.
The first 5 of 14 adult men with hemophilia A and who had factor VIII (FVIII) activity of 2% or less before treatment with SPK-8011 (at single doses of either 5 × 1011 or 1 × 1012 vg/kg), showed no development of FVIII inhibitors or evidence of FVIII cellular immune response at 106-142 weeks’ follow-up after vector infusion, according to Lindsey A. George, MD, at the International Society of Thrombosis and Haemostasis 2020 virtual congress.
At follow-up, the two who had received a 5 × 1011 vg/kg dose had FVIII activity of 6.9%-8.4%, and the three in the 1 × 1012 vg/kg cohort had FVIII activity of 5.2%-19.8%, said Dr. George, of the Children’s Hospital of Philadelphia.
Overall, 12 of the 14 patients in the study had sustained FVIII expression, including 7 of 9 who received the highest SPK-8011 dose of 2 × 1012 vg/kg. In the 12 with sustained expression, a “remarkable” 91% reduction in the annualized bleeding rate from the year prior to vs. the year after vector infusion was observed, she said.
“Similarly, looking at number of factor infusions before vector infusion relative to the number of factor infusions after vector infusion ... [there was] evidence of remarkable preliminary efficacy,” she added, noting a 96% reduction in factor consumption.
The findings are of note because, while clinical studies of Spark Therapeutic’s SPK-8011 product in hemophilia B and preclinical models in hemophilia A showed promising reductions in bleeds and stable, durable levels of FVIII expression after therapy, the first successful clinical trial of an AAV-mediated gene therapy in hemophilia A – the BioMarin AAV serotype 5 human FVIII-SQ (valoctocogene roxaparvovec) – showed an unexpected decline in FVIII expression at 1, 2, 3, and 4 years.
“This may be particularly relevant in the context of development of multi-serotype AAV neutralizing antibodies (NAb) following AAV vector administration,” Dr. George said, referencing a small study in which she and her colleagues showed long-term persistence of cross-reactive AAV NAb. The findings of that study, which is currently in press in Molecular Therapy, “suggest that repeat AAV vector infusion is unlikely to be possible with current methods.”
Initial results from the SPK-8011 study were presented at the 2018 American Society of Hematology annual meeting. No major safety issues have emerged since those data were presented at ASH; no deaths have occurred, and none of the patients developed FVIII inhibitors.
Treatment-related adverse events were limited to an infusion reaction in one patient, which resolved completely, and liver enzyme elevations in three patients, which also resolved. One serious adverse event – a grade 2 transaminitis that resulted in elective hospitalization for intravenous steroid administration, also resolved.
With respect to vector clearance, there was “no evidence of vector in either saliva, semen, serum, urine, or peripheral blood mononuclear cells by 6 weeks after vector infusion,” Dr. George said.
One-stage assay determination of FVIII activity showed that activity greater than 10% permits an absolute bleeding rate (ABR) of less than 1%, which is consistent with hemophilia natural history studies. Therefore “these data support that FVIII activity that is approximately greater than 10% “may be adequate to either eliminate or achieve an ABR of less than 1,” she said.
“With respect to assay discrepancy, our data at least preliminarily support that the one-stage assay determinant of hepatocyte-derived FVIII correlates with clinical phenotype,” she added.
The findings in the first five patients demonstrate preliminary stability of FVIII expression at follow up between 2 and 3.3 years, she said.
Further, of the nine patients who received the 2 × 1012 vg/kg dose, seven had sustained FVIII expression at about 1.5 years, five of the seven had no bleeds, and two lost FVIII expression and returned to prophylaxis uneventfully, she noted.
“The future directions of this work are ultimately to explore the optimal vector dose and immunosuppression regimens to achieve predictable, safe, efficacious, and durable FVIII expression,” she said.
Asked during a question and answer period about potential reasons for the differences in durability seen with SBK-8011 versus valoctocogene roxaparvovec, Dr. George said they remain unclear but could be related to differences in vector doses and manufacturing platforms.
Emerging data may allow for better comparisons, she added.
Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de Recherche des Cordeliers, Paris, further asked about plans to optimize the immunosuppression regimen.
Plans are indeed in the works to identify the optimal immunosuppression regimen and to optimize immunosuppression in this trial, Dr. George said, noting that Spark Therapeutics “has outlined a plan to further investigate this in phase 1/2 trial before progressing into phase 3 study.”
Spark Therapeutic sponsored the SPK-8011 study. Dr. George disclosed consulting and/or data safety monitoring board activity for Pfizer and AvroBio.
SOURCE: George L et al. 2020 ISTH Congress, Abstract OC 03.5.
SPK-8011, an investigational adeno-associated virus (AAV)–mediated gene therapy for hemophilia A, provides stable and durable factor VIII expression with no major safety concerns, according to findings at least 2 years after a single treatment in patients from a phase 1/2 trial.
The first 5 of 14 adult men with hemophilia A and who had factor VIII (FVIII) activity of 2% or less before treatment with SPK-8011 (at single doses of either 5 × 1011 or 1 × 1012 vg/kg), showed no development of FVIII inhibitors or evidence of FVIII cellular immune response at 106-142 weeks’ follow-up after vector infusion, according to Lindsey A. George, MD, at the International Society of Thrombosis and Haemostasis 2020 virtual congress.
At follow-up, the two who had received a 5 × 1011 vg/kg dose had FVIII activity of 6.9%-8.4%, and the three in the 1 × 1012 vg/kg cohort had FVIII activity of 5.2%-19.8%, said Dr. George, of the Children’s Hospital of Philadelphia.
Overall, 12 of the 14 patients in the study had sustained FVIII expression, including 7 of 9 who received the highest SPK-8011 dose of 2 × 1012 vg/kg. In the 12 with sustained expression, a “remarkable” 91% reduction in the annualized bleeding rate from the year prior to vs. the year after vector infusion was observed, she said.
“Similarly, looking at number of factor infusions before vector infusion relative to the number of factor infusions after vector infusion ... [there was] evidence of remarkable preliminary efficacy,” she added, noting a 96% reduction in factor consumption.
The findings are of note because, while clinical studies of Spark Therapeutic’s SPK-8011 product in hemophilia B and preclinical models in hemophilia A showed promising reductions in bleeds and stable, durable levels of FVIII expression after therapy, the first successful clinical trial of an AAV-mediated gene therapy in hemophilia A – the BioMarin AAV serotype 5 human FVIII-SQ (valoctocogene roxaparvovec) – showed an unexpected decline in FVIII expression at 1, 2, 3, and 4 years.
“This may be particularly relevant in the context of development of multi-serotype AAV neutralizing antibodies (NAb) following AAV vector administration,” Dr. George said, referencing a small study in which she and her colleagues showed long-term persistence of cross-reactive AAV NAb. The findings of that study, which is currently in press in Molecular Therapy, “suggest that repeat AAV vector infusion is unlikely to be possible with current methods.”
Initial results from the SPK-8011 study were presented at the 2018 American Society of Hematology annual meeting. No major safety issues have emerged since those data were presented at ASH; no deaths have occurred, and none of the patients developed FVIII inhibitors.
Treatment-related adverse events were limited to an infusion reaction in one patient, which resolved completely, and liver enzyme elevations in three patients, which also resolved. One serious adverse event – a grade 2 transaminitis that resulted in elective hospitalization for intravenous steroid administration, also resolved.
With respect to vector clearance, there was “no evidence of vector in either saliva, semen, serum, urine, or peripheral blood mononuclear cells by 6 weeks after vector infusion,” Dr. George said.
One-stage assay determination of FVIII activity showed that activity greater than 10% permits an absolute bleeding rate (ABR) of less than 1%, which is consistent with hemophilia natural history studies. Therefore “these data support that FVIII activity that is approximately greater than 10% “may be adequate to either eliminate or achieve an ABR of less than 1,” she said.
“With respect to assay discrepancy, our data at least preliminarily support that the one-stage assay determinant of hepatocyte-derived FVIII correlates with clinical phenotype,” she added.
The findings in the first five patients demonstrate preliminary stability of FVIII expression at follow up between 2 and 3.3 years, she said.
Further, of the nine patients who received the 2 × 1012 vg/kg dose, seven had sustained FVIII expression at about 1.5 years, five of the seven had no bleeds, and two lost FVIII expression and returned to prophylaxis uneventfully, she noted.
“The future directions of this work are ultimately to explore the optimal vector dose and immunosuppression regimens to achieve predictable, safe, efficacious, and durable FVIII expression,” she said.
Asked during a question and answer period about potential reasons for the differences in durability seen with SBK-8011 versus valoctocogene roxaparvovec, Dr. George said they remain unclear but could be related to differences in vector doses and manufacturing platforms.
Emerging data may allow for better comparisons, she added.
Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de Recherche des Cordeliers, Paris, further asked about plans to optimize the immunosuppression regimen.
Plans are indeed in the works to identify the optimal immunosuppression regimen and to optimize immunosuppression in this trial, Dr. George said, noting that Spark Therapeutics “has outlined a plan to further investigate this in phase 1/2 trial before progressing into phase 3 study.”
Spark Therapeutic sponsored the SPK-8011 study. Dr. George disclosed consulting and/or data safety monitoring board activity for Pfizer and AvroBio.
SOURCE: George L et al. 2020 ISTH Congress, Abstract OC 03.5.
SPK-8011, an investigational adeno-associated virus (AAV)–mediated gene therapy for hemophilia A, provides stable and durable factor VIII expression with no major safety concerns, according to findings at least 2 years after a single treatment in patients from a phase 1/2 trial.
The first 5 of 14 adult men with hemophilia A and who had factor VIII (FVIII) activity of 2% or less before treatment with SPK-8011 (at single doses of either 5 × 1011 or 1 × 1012 vg/kg), showed no development of FVIII inhibitors or evidence of FVIII cellular immune response at 106-142 weeks’ follow-up after vector infusion, according to Lindsey A. George, MD, at the International Society of Thrombosis and Haemostasis 2020 virtual congress.
At follow-up, the two who had received a 5 × 1011 vg/kg dose had FVIII activity of 6.9%-8.4%, and the three in the 1 × 1012 vg/kg cohort had FVIII activity of 5.2%-19.8%, said Dr. George, of the Children’s Hospital of Philadelphia.
Overall, 12 of the 14 patients in the study had sustained FVIII expression, including 7 of 9 who received the highest SPK-8011 dose of 2 × 1012 vg/kg. In the 12 with sustained expression, a “remarkable” 91% reduction in the annualized bleeding rate from the year prior to vs. the year after vector infusion was observed, she said.
“Similarly, looking at number of factor infusions before vector infusion relative to the number of factor infusions after vector infusion ... [there was] evidence of remarkable preliminary efficacy,” she added, noting a 96% reduction in factor consumption.
The findings are of note because, while clinical studies of Spark Therapeutic’s SPK-8011 product in hemophilia B and preclinical models in hemophilia A showed promising reductions in bleeds and stable, durable levels of FVIII expression after therapy, the first successful clinical trial of an AAV-mediated gene therapy in hemophilia A – the BioMarin AAV serotype 5 human FVIII-SQ (valoctocogene roxaparvovec) – showed an unexpected decline in FVIII expression at 1, 2, 3, and 4 years.
“This may be particularly relevant in the context of development of multi-serotype AAV neutralizing antibodies (NAb) following AAV vector administration,” Dr. George said, referencing a small study in which she and her colleagues showed long-term persistence of cross-reactive AAV NAb. The findings of that study, which is currently in press in Molecular Therapy, “suggest that repeat AAV vector infusion is unlikely to be possible with current methods.”
Initial results from the SPK-8011 study were presented at the 2018 American Society of Hematology annual meeting. No major safety issues have emerged since those data were presented at ASH; no deaths have occurred, and none of the patients developed FVIII inhibitors.
Treatment-related adverse events were limited to an infusion reaction in one patient, which resolved completely, and liver enzyme elevations in three patients, which also resolved. One serious adverse event – a grade 2 transaminitis that resulted in elective hospitalization for intravenous steroid administration, also resolved.
With respect to vector clearance, there was “no evidence of vector in either saliva, semen, serum, urine, or peripheral blood mononuclear cells by 6 weeks after vector infusion,” Dr. George said.
One-stage assay determination of FVIII activity showed that activity greater than 10% permits an absolute bleeding rate (ABR) of less than 1%, which is consistent with hemophilia natural history studies. Therefore “these data support that FVIII activity that is approximately greater than 10% “may be adequate to either eliminate or achieve an ABR of less than 1,” she said.
“With respect to assay discrepancy, our data at least preliminarily support that the one-stage assay determinant of hepatocyte-derived FVIII correlates with clinical phenotype,” she added.
The findings in the first five patients demonstrate preliminary stability of FVIII expression at follow up between 2 and 3.3 years, she said.
Further, of the nine patients who received the 2 × 1012 vg/kg dose, seven had sustained FVIII expression at about 1.5 years, five of the seven had no bleeds, and two lost FVIII expression and returned to prophylaxis uneventfully, she noted.
“The future directions of this work are ultimately to explore the optimal vector dose and immunosuppression regimens to achieve predictable, safe, efficacious, and durable FVIII expression,” she said.
Asked during a question and answer period about potential reasons for the differences in durability seen with SBK-8011 versus valoctocogene roxaparvovec, Dr. George said they remain unclear but could be related to differences in vector doses and manufacturing platforms.
Emerging data may allow for better comparisons, she added.
Session moderator Sebastien Lacroix-Desmazes, MD, of Centre de Recherche des Cordeliers, Paris, further asked about plans to optimize the immunosuppression regimen.
Plans are indeed in the works to identify the optimal immunosuppression regimen and to optimize immunosuppression in this trial, Dr. George said, noting that Spark Therapeutics “has outlined a plan to further investigate this in phase 1/2 trial before progressing into phase 3 study.”
Spark Therapeutic sponsored the SPK-8011 study. Dr. George disclosed consulting and/or data safety monitoring board activity for Pfizer and AvroBio.
SOURCE: George L et al. 2020 ISTH Congress, Abstract OC 03.5.
FROM THE 2020 ISTH CONGRESS
One-third of outpatients with COVID-19 are unwell weeks later
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
, according to survey results in Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention.
Mark W. Tenforde, MD, PhD, for the CDC-COVID-19 Response Team, and colleagues conducted a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2. The researchers found that 35% had not returned to their usual state of wellness when they were interviewed 2-3 weeks after testing.
Among the 270 of 274 people interviewed for whom there were data on return to health, 175 (65%) reported that they had returned to baseline health an average of 7 days from the date of testing.
Among the 274 symptomatic outpatients, the median number of symptoms was seven. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms.
Prolonged illness is well described in adults hospitalized with severe COVID-19, especially among the older adult population, but little is known about other groups.
The proportion who had not returned to health differed by age: 26% of interviewees aged 18-34 years, 32% of those aged 35-49 years, and 47% of those at least 50 years old reported not having returned to their usual health (P = .010) within 14-21 days after receiving positive test results.
Among respondents aged 18-34 years who had no chronic medical condition, 19% (9 of 48) reported not having returned to their usual state of health during that time.
Public health messaging targeting younger adults, a group who might not be expected to be sick for weeks with mild disease, is particularly important, the authors wrote.
Kyle Annen, DO, medical director of transfusion services and patient blood management at Children’s Hospital Colorado and assistant professor of pathology at the University of Colorado, Denver, said in an interview that an important message is that delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization.
“This should impact the perception of this being a mild illness in the young adult population and encourage them to comply with recommendations of social distancing, masking, and hand washing,” she said.
Recovery time of more than 2 weeks will affect work and school performance, especially prolonged fatigue, she noted. This was one of the prominent symptoms that were reported to be slow to dissipate.
“I think the most interesting point in this study is that of underlying conditions; psychiatric conditions were significantly correlated with prolonged recovery. I don’t think that many people think of depression and anxiety as an underlying medical condition in regards to COVID-19 risk. This could potentially have an impact, as depression and anxiety rates will likely increase as COVID-19 continues,” she said.
Buddy Creech, MD, MPH, said in an interview that it is “important to realize that the spectrum of disease with COVID is wide, including mild disease, severe disease, and prolonged disease. This report helps us understand some of the risk factors for those with prolonged symptoms and may allow us to refine even more clearly how we prioritize treatment and vaccine administration, once available.
“It also highlights the challenge of dealing with this virus. Not only do the symptoms vary widely, but so do the incubation period, the duration of symptoms, and the residual symptoms that sometimes occur. Clearly, there is much we still need to understand about this virus,” he said.
The interviews were conducted from April 15 to June 25 with a random sample of adults at least 18 years old who had received a first positive test result for SARS-CoV-2 at an outpatient visit at one of 14 US academic healthcare systems in 13 states.
A version of this article originally appeared on Medscape.com.
Small NY study: Mother-baby transmission of COVID-19 not seen
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
FROM PEDIATRICS
Men occupy most leadership roles in medicine
Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but according to an update provided at the virtual Pediatric Hospital Medicine.
In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.
“No matter how you slice it, women are underrepresented in leadership positions,” he noted.
The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.
According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.
Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.
“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.
The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.
“There is certainly no shortage of capable women,” he noted.
Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.
The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”
Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”
However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.
In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”
There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.
Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.
“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.
“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.
Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.
“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.
Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.
Dr. Chiang reported no potential conflicts of interest relevant to this study.
Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but according to an update provided at the virtual Pediatric Hospital Medicine.
In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.
“No matter how you slice it, women are underrepresented in leadership positions,” he noted.
The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.
According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.
Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.
“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.
The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.
“There is certainly no shortage of capable women,” he noted.
Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.
The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”
Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”
However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.
In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”
There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.
Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.
“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.
“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.
Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.
“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.
Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.
Dr. Chiang reported no potential conflicts of interest relevant to this study.
Since the early 2000s, approximately half of medical students in the United States – and in many years, more than half – have been women, but according to an update provided at the virtual Pediatric Hospital Medicine.
In pediatrics, a specialty in which approximately 70% of physicians are now women, there has been progress, but still less than 30% of pediatric department chairs are female, said Vincent Chiang, MD, chief medical officer of Boston Children’s Hospital, during a presentation at the virtual meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
Citing published data and a survey he personally conducted of the top children’s hospitals identified by the U.S. News and World Report, Dr. Chiang said a minority of division chiefs, chief medical officers, chief financial officers, and other leaders are female. At his institution, only 2 of 16 division chiefs are female.
“No matter how you slice it, women are underrepresented in leadership positions,” he noted.
The problem is certainly not confined to medicine. Dr. Chiang cited data showing that women and men have reached “near parity” in workforce participation in the United States even though the 20% earnings gap has changed little over time.
According to 2020 data from the World Economic Forum, the United States ranked 51 for the gender gap calculated on the basis of economic, political, educational, and health attainment. Even if this places the United States in the top third of the rankings, it is far behind Iceland and the Scandinavian countries that lead the list.
Efforts to reduce structural biases are part of the fix, but Dr. Chiang cautioned that fundamental changes might never occur if the plan is to wait for an approach based on meritocracy. He said that existing structural biases are “slanted away from women,” who are not necessarily granted the opportunities that are readily available to men.
“A meritocracy only works if the initial playing field was level. Otherwise, it just perpetuates the inequalities,” he said.
The problem is not a shortage of women with the skills to lead. In a study by Zenger/Folkman, a consulting company that works on leadership skill development, women performed better than men in 16 of 18 leadership categories, according to Dr. Chiang.
“There is certainly no shortage of capable women,” he noted.
Of the many issues, Dr. Chiang highlighted two. The first is the challenge of placing women on leadership pathways. This is likely to require proactive strategies, such as fast-track advancement programs that guide female candidates toward leadership roles.
The second is more nuanced. According to Dr. Chiang, women who want to assume a leadership role should think more actively about how and who is making decisions at their institution so they can position themselves appropriately. This is nuanced because “there is a certain amount of gamesmanship,” he said. The rise to leadership “has never been a pure meritocracy.”
Importantly, many of the key decisions in any institution involve money, according to Dr. Chiang. As a result, he advised those seeking leadership roles to join audit committees or otherwise take on responsibility for profit-and-loss management. Even in a nonprofit institution, “you need to make the numbers work,” he said, citing the common catchphrase: “No margin, no mission.”
However, Dr. Chiang acknowledged the many obstacles that prevent women from working their way into positions of leadership. For example, networking is important, but women are not necessarily attracted or invited to some of the social engagements, such as golf outings, where strong relationships are created.
In a survey of 100,000 people working at Fortune 500 companies, “82% of women say they feel excluded at work and much of that comes from that informal networking,” Dr. Chiang said. “Whereas 92% of men think they are not excluding women in their daily work.”
There is no single solution, but Dr. Chiang believes that concrete structural changes are needed. Female doctors remain grossly underrepresented in leadership roles even as they now represent more than half of the workforce for many specialties. Based on the need for proactive approaches outlined by Dr. Chiang, it appears unlikely that gender inequality will ever resolve itself.
Lisa S. Rotenstein, MD, who has written on fixing the gender imbalance in health care, including for the Harvard Business Review, said she agreed during an interview that structural changes are critical.
“In order to address current disparities, leaders should be thinking about how to remove both the formal and informal obstacles that prevent women and minorities from getting into the rooms where these decisions are being made,” said Dr. Rotenstein, who is an instructor in medicine at Brigham and Women’s Hospital, Harvard Medical School in Boston.
“This will need to involve sponsorship that gets women invited to the right committees or in positions with responsibility for profit-and-loss management,” she added.
Dr. Rotenstein spoke about improving “access to the pipeline” that leads to leadership roles. The ways in which women are excluded from opportunities is often subtle and difficult to penetrate without fundamental changes, she explained.
“Institutions need to understand the processes that lead to leadership roles and make the changes that allow women and minorities to participate,” she said. It is not enough to recognize the problem, according to Dr. Rotenstein.
Like Dr. Chiang, she noted that changes are needed in the methods that move underrepresented groups into leadership roles.
Dr. Chiang reported no potential conflicts of interest relevant to this study.
FROM PHM20
Migraine headache pearls
A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.
She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
A. Topiramate
B. Beta-blocker
C. Lasmiditan
D. Metoclopramide plus sumatriptan
E. Ubrogepant
It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies.
For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.
When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.1 Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.
Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.
Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.2
In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.3 There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.
Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.4 In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).
In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).5
Pearl
Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.
2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.
3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.
4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.
5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.
A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.
She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
A. Topiramate
B. Beta-blocker
C. Lasmiditan
D. Metoclopramide plus sumatriptan
E. Ubrogepant
It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies.
For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.
When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.1 Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.
Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.
Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.2
In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.3 There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.
Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.4 In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).
In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).5
Pearl
Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.
2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.
3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.
4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.
5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.
A 25-year-old woman presents to discuss treatment of her headaches. They occur two or three times a month and last for 4-6 hours. The headaches are disabling, have a pounding quality behind the patient’s right eye, and worsen with exercise. The patient’s neurologic exam is normal.
She has tried oral sumatriptan and naproxen, but neither drug provided her with any relief from the headaches. What treatment would you recommend?
A. Topiramate
B. Beta-blocker
C. Lasmiditan
D. Metoclopramide plus sumatriptan
E. Ubrogepant
It is common to see patients with migraine headaches and to see patients with migraines who have not responded to previous migraine therapies.
For this patient, I would try choice D first, giving metoclopramide with oral sumatriptan to see if it can improve response to sumatriptan. The two new classes of drugs for acute migraine therapy, the gepants and ditans, certainly have a role in patients unresponsive or intolerant of triptans/NSAIDS, but I would try several tricks with these less expensive medications first before entering into prior authorization hell trying to get a gepant or ditan.
When a patient has already used a triptan but experienced no benefit from it, often the next medication a patient tries is a different triptan. Dahlof reviewed four trials that looked at the efficacy of switching sumatriptan nonresponders to a different triptan and found that lack of response to sumatriptan did not predict lack of response to an alternative triptan.1 Unfortunately, acquiring insurance coverage for an alternate triptan can be difficult.
Other treatment options are nasal or injectable formulations of sumatriptan. Both of these are more costly than oral sumatriptan, and injectable sumatriptan has more side effects than oral triptans.
Combining treatment with metoclopramide can be helpful. In a study by Schulman and Dermott looking at patients who had previously been triptan nonresponders, 63% of those who took metoclopramide with sumatriptan had meaningful pain relief, compared with 31% of those who received sumatriptan and placebo.2
In a different study, Tfelt-Hansen et al. compared treatment with the combination of lysine acetylsalicylate plus metoclopramide versus treatment with 100 mg of sumatriptan.3 There was no difference in outcomes between the two treatment groups, with the lysine acetylsalicylate plus metoclopramide patients having a 57% success rate for first treated migraine compared with 53% of the sumatriptan-treated patients.
Treating with the combination of naproxen plus sumatriptan is superior to treating with either medication alone. Brandes et al. reported on two studies involving the use of the sumatriptan/naproxen combination, compared with using sumatriptan, naproxen, or placebo.4 In both, taking the sumatriptan/naproxen combination was superior to taking sumatriptan, naproxen, or placebo (P < .001).
In a study of patients with poor prior response to triptans, Mathew et al. found that the sumatriptan/naproxen combination was superior to placebo for both 2- and 24-hour headache relief (P < .001).5
Pearl
Try several options before abandoning triptans in previous triptan nonresponders, including trying a different triptan, adding metoclopramide, orcombining with an NSAID.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.
References
1. Dahlöf CG. Infrequent or nonresponse to oral sumatriptan does not predict response to other triptans – review of four trials. Cephalalgia. 2006 Feb;26(2):98-106.
2. Schulman EA, Dermott KF. Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs. Headache. 2003 Jul-Aug;43(7):729-33.
3. Tfelt-Hansen P et al. The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet. 1995 Oct 7;346(8980):923-6.
4. Brandes JL et al. Sumatriptan‐naproxen for acute treatment of migraine: A randomized trial. JAMA. 2007;297:1443‐54.
5. Mathew NT, Landy S, Stark S, et al. Fixed‐dose sumatriptan and naproxen in poor responders to triptans with a short half‐life. Headache. 2009;49:971‐82.
FDA allows qualified claims for UTI risk reduction with cranberry products
The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.
In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.
After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.
The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.
The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.
“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.
“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.
“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.
Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.
“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”
Dr. Bohon had no relevant financial conflicts to disclose.
The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.
In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.
After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.
The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.
The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.
“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.
“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.
“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.
Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.
“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”
Dr. Bohon had no relevant financial conflicts to disclose.
The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.
In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.
After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.
The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.
The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”
The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.
“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.
“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.
“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.
Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.
“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”
Dr. Bohon had no relevant financial conflicts to disclose.
Internists still low for earnings and net worth, report finds
according to the Medscape Internist Debt and Net Worth Report 2020.
The results are from a larger survey that tracked physicians’ efforts to reduce or eliminate debt, save, invest, purchase property, and prepare for retirement. The annual survey was completed just as the COVID-19 pandemic was taking hold, and the findings provide a baseline against which to view the effects of the pandemic, which turned the lives of many physicians upside down.
Conducted from Oct. 4, 2019, until Feb. 10, 2020, the survey represents 17,461 physicians from 29 areas of medicine, including family practice, internal medicine, pediatrics, and obstetrics and gynecology.
Earnings and net worth
Internists earned on average $251,000 annually, sixth from the bottom of the list and approximately half the amount of the most lucrative specialty, orthopedics. The annual salary increased from $243,000 in 2019.
The average annual salary for internists represents a 2.5% increase, compared with the 1.5% increase for specialists, whose annual income rose from $341,000 in 2019 to $346,000 in 2020.
The low earnings for internists are echoed in the findings for net worth: 58% of internists have a net worth of less than $1 million, 37% have between $1 million and $5 million, and 5% have more than $5 million. For comparison, half of all physicians have a net worth of less than $1 million, 42% have between $1 million and $5 million, and 8% have over $5 million.
About 40% of internists indicated that their net worth was less than $500,000, which is the fourth highest of the 29 medical fields surveyed. About 44% of pediatricians, 46% of family practitioners, and 30% of ob.gyns. also reported their net worth at less than $500,000, so the primary care providers share low net worth compared with their colleagues. About 41% of neurologists reported a net worth of less than $500,000.
Only 5% of internists reported a net worth of more than $5 million. The specialties with the most physicians with net worth exceeding $5 million are orthopedists, at 19%, and plastic surgeons and gastroenterologists, each at 16%.
Gender disparity in net worth appears to be lower among internists than in other fields. Among all physicians, 56% of men and 39% of women reported a net worth in excess of $1 million, but among internists, 46% of men and 36% of women did so. About 64% of the internists who took the survey are men, and 34% are women.
Higher net worth tracks clearly with age group, as expected in light of diminishing debt over time and an accumulation of wealth.
Expenses
The top three expenses that internists face are mortgage on primary residence (60%), car loans (36%), and credit card debt (26%); 12% of respondents reported no debt or expenses. Among all physicians, the breakdown of expenses by category is very similar to that for internists.
Paying off school loans affects 24% of internists, which was in the middle of the 29 physician groups. The percentage ranges from physical medicine and rehabilitation at 34% to rheumatology at 15%.
About 42% of internists have a mortgage of less than $300,000, and 30% have no mortgage at all. Figures are similar for all physicians.
Internists are apparently savers and not spenders. Only 8% reported living above their means; 39% indicated that they live below their means. These figures are similar for all physicians who responded to the survey.
About 60% of internists put more than $1,000 a month into tax-deferred accounts. Most internists also contribute to taxable savings accounts, which might reflect the fact that they had contributed the maximum amount to tax-deferred accounts.
Two-fifths of the internists reported having worked with a financial planner. Of the nearly three fourths of responding internists who share finances with a spouse or partner, a few more than half pool resources.
In the world before COVID-19, 31% of internists reported significant financial losses over the previous year, most because of bad investments or problems relating to their practice. Financial losses since that time obviously have another predominant cause – the direct and ripple effects of the pandemic.
As of July 22, primary care providers reported a 55% decrease in revenue and a 20%-30% decrease in patient volume, according to Travis Singleton, senior vice president of Merritt Hawkins, a physician placement and recruiting company. Some practitioners have closed their physical offices because patient demand has plummeted and nonessential office procedures and exams have been postponed or canceled. The use of telemedicine has soared.
Medscape’s Internist Debt and Net Worth Report 2020, and the larger report from which it was derived, may come to serve as a marker between two very different financial worlds for clinical medicine.
A version of this article originally appeared on Medscape.com.
according to the Medscape Internist Debt and Net Worth Report 2020.
The results are from a larger survey that tracked physicians’ efforts to reduce or eliminate debt, save, invest, purchase property, and prepare for retirement. The annual survey was completed just as the COVID-19 pandemic was taking hold, and the findings provide a baseline against which to view the effects of the pandemic, which turned the lives of many physicians upside down.
Conducted from Oct. 4, 2019, until Feb. 10, 2020, the survey represents 17,461 physicians from 29 areas of medicine, including family practice, internal medicine, pediatrics, and obstetrics and gynecology.
Earnings and net worth
Internists earned on average $251,000 annually, sixth from the bottom of the list and approximately half the amount of the most lucrative specialty, orthopedics. The annual salary increased from $243,000 in 2019.
The average annual salary for internists represents a 2.5% increase, compared with the 1.5% increase for specialists, whose annual income rose from $341,000 in 2019 to $346,000 in 2020.
The low earnings for internists are echoed in the findings for net worth: 58% of internists have a net worth of less than $1 million, 37% have between $1 million and $5 million, and 5% have more than $5 million. For comparison, half of all physicians have a net worth of less than $1 million, 42% have between $1 million and $5 million, and 8% have over $5 million.
About 40% of internists indicated that their net worth was less than $500,000, which is the fourth highest of the 29 medical fields surveyed. About 44% of pediatricians, 46% of family practitioners, and 30% of ob.gyns. also reported their net worth at less than $500,000, so the primary care providers share low net worth compared with their colleagues. About 41% of neurologists reported a net worth of less than $500,000.
Only 5% of internists reported a net worth of more than $5 million. The specialties with the most physicians with net worth exceeding $5 million are orthopedists, at 19%, and plastic surgeons and gastroenterologists, each at 16%.
Gender disparity in net worth appears to be lower among internists than in other fields. Among all physicians, 56% of men and 39% of women reported a net worth in excess of $1 million, but among internists, 46% of men and 36% of women did so. About 64% of the internists who took the survey are men, and 34% are women.
Higher net worth tracks clearly with age group, as expected in light of diminishing debt over time and an accumulation of wealth.
Expenses
The top three expenses that internists face are mortgage on primary residence (60%), car loans (36%), and credit card debt (26%); 12% of respondents reported no debt or expenses. Among all physicians, the breakdown of expenses by category is very similar to that for internists.
Paying off school loans affects 24% of internists, which was in the middle of the 29 physician groups. The percentage ranges from physical medicine and rehabilitation at 34% to rheumatology at 15%.
About 42% of internists have a mortgage of less than $300,000, and 30% have no mortgage at all. Figures are similar for all physicians.
Internists are apparently savers and not spenders. Only 8% reported living above their means; 39% indicated that they live below their means. These figures are similar for all physicians who responded to the survey.
About 60% of internists put more than $1,000 a month into tax-deferred accounts. Most internists also contribute to taxable savings accounts, which might reflect the fact that they had contributed the maximum amount to tax-deferred accounts.
Two-fifths of the internists reported having worked with a financial planner. Of the nearly three fourths of responding internists who share finances with a spouse or partner, a few more than half pool resources.
In the world before COVID-19, 31% of internists reported significant financial losses over the previous year, most because of bad investments or problems relating to their practice. Financial losses since that time obviously have another predominant cause – the direct and ripple effects of the pandemic.
As of July 22, primary care providers reported a 55% decrease in revenue and a 20%-30% decrease in patient volume, according to Travis Singleton, senior vice president of Merritt Hawkins, a physician placement and recruiting company. Some practitioners have closed their physical offices because patient demand has plummeted and nonessential office procedures and exams have been postponed or canceled. The use of telemedicine has soared.
Medscape’s Internist Debt and Net Worth Report 2020, and the larger report from which it was derived, may come to serve as a marker between two very different financial worlds for clinical medicine.
A version of this article originally appeared on Medscape.com.
according to the Medscape Internist Debt and Net Worth Report 2020.
The results are from a larger survey that tracked physicians’ efforts to reduce or eliminate debt, save, invest, purchase property, and prepare for retirement. The annual survey was completed just as the COVID-19 pandemic was taking hold, and the findings provide a baseline against which to view the effects of the pandemic, which turned the lives of many physicians upside down.
Conducted from Oct. 4, 2019, until Feb. 10, 2020, the survey represents 17,461 physicians from 29 areas of medicine, including family practice, internal medicine, pediatrics, and obstetrics and gynecology.
Earnings and net worth
Internists earned on average $251,000 annually, sixth from the bottom of the list and approximately half the amount of the most lucrative specialty, orthopedics. The annual salary increased from $243,000 in 2019.
The average annual salary for internists represents a 2.5% increase, compared with the 1.5% increase for specialists, whose annual income rose from $341,000 in 2019 to $346,000 in 2020.
The low earnings for internists are echoed in the findings for net worth: 58% of internists have a net worth of less than $1 million, 37% have between $1 million and $5 million, and 5% have more than $5 million. For comparison, half of all physicians have a net worth of less than $1 million, 42% have between $1 million and $5 million, and 8% have over $5 million.
About 40% of internists indicated that their net worth was less than $500,000, which is the fourth highest of the 29 medical fields surveyed. About 44% of pediatricians, 46% of family practitioners, and 30% of ob.gyns. also reported their net worth at less than $500,000, so the primary care providers share low net worth compared with their colleagues. About 41% of neurologists reported a net worth of less than $500,000.
Only 5% of internists reported a net worth of more than $5 million. The specialties with the most physicians with net worth exceeding $5 million are orthopedists, at 19%, and plastic surgeons and gastroenterologists, each at 16%.
Gender disparity in net worth appears to be lower among internists than in other fields. Among all physicians, 56% of men and 39% of women reported a net worth in excess of $1 million, but among internists, 46% of men and 36% of women did so. About 64% of the internists who took the survey are men, and 34% are women.
Higher net worth tracks clearly with age group, as expected in light of diminishing debt over time and an accumulation of wealth.
Expenses
The top three expenses that internists face are mortgage on primary residence (60%), car loans (36%), and credit card debt (26%); 12% of respondents reported no debt or expenses. Among all physicians, the breakdown of expenses by category is very similar to that for internists.
Paying off school loans affects 24% of internists, which was in the middle of the 29 physician groups. The percentage ranges from physical medicine and rehabilitation at 34% to rheumatology at 15%.
About 42% of internists have a mortgage of less than $300,000, and 30% have no mortgage at all. Figures are similar for all physicians.
Internists are apparently savers and not spenders. Only 8% reported living above their means; 39% indicated that they live below their means. These figures are similar for all physicians who responded to the survey.
About 60% of internists put more than $1,000 a month into tax-deferred accounts. Most internists also contribute to taxable savings accounts, which might reflect the fact that they had contributed the maximum amount to tax-deferred accounts.
Two-fifths of the internists reported having worked with a financial planner. Of the nearly three fourths of responding internists who share finances with a spouse or partner, a few more than half pool resources.
In the world before COVID-19, 31% of internists reported significant financial losses over the previous year, most because of bad investments or problems relating to their practice. Financial losses since that time obviously have another predominant cause – the direct and ripple effects of the pandemic.
As of July 22, primary care providers reported a 55% decrease in revenue and a 20%-30% decrease in patient volume, according to Travis Singleton, senior vice president of Merritt Hawkins, a physician placement and recruiting company. Some practitioners have closed their physical offices because patient demand has plummeted and nonessential office procedures and exams have been postponed or canceled. The use of telemedicine has soared.
Medscape’s Internist Debt and Net Worth Report 2020, and the larger report from which it was derived, may come to serve as a marker between two very different financial worlds for clinical medicine.
A version of this article originally appeared on Medscape.com.
‘Defending Jacob’ and defending psychiatry
The 2012 crime fiction novel, “Defending Jacob,” by William Landay was dramatized into a miniseries created by Mark Bomback that premiered on April 24, 2020, on Apple TV+ (and for those resisting a subscription, “The Morning Show” and “Defending Jacob” are both worth it). Both the “Defending Jacob” novel and the miniseries have themes that are of interest to psychiatry, especially to child and forensic psychiatrists, and both the literary and TV versions are excellent, albeit disturbing, diversions from the current pandemic.
(Spoiler alert!) The story is set in the affluent town of Newton, Mass., where crime is generally low and homicides extremely infrequent. Protagonist Andy Barber, a 51-year-old Jewish assistant district attorney, is played by a younger Chris Evans in the miniseries. His wife, Laurie Gold Barber, a 51-year-old Jewish former schoolteacher and stay-at-home mom, is played by a younger Michelle Dockery of Downton Abbey fame. In the miniseries, her character is actively working as a teacher and social activist for children. Other differences between the novel and the miniseries will be pointed out when relevant, but the overall narrative is similar. Both stories are cleverly told through Andy Barber speaking in retrospect as he is being questioned in front of a grand jury for a potential indictment.
When 14-year-old Ben Rifkin is found stabbed to death in Cold Spring Park before school one morning, Andy Barber initially takes the case despite his boss’s reservations that there may be a conflict because Andy’s son Jacob is a student in Ben’s class at school. As the title suggests, it soon becomes clear that Jacob may have had something to do with the murder. At that point, Andy is taken off the case and it is given to a junior colleague, Neal Logiudice, who demonstrates both admiration and contempt for his former mentor, perhaps because of underlying jealousy and insecurity. Neal Logiudice becomes the DA questioning Andy Barber.
Prior to Jacob’s formal accusation of murder, the Barbers appear to be fiercely loyal and unable to fully see and understand their son. The difficulty with objectivity and the reasons why family member physicians should never treat family members – and why family member attorneys should never represent loved ones – is abundantly clear in this story. When Andy receives an anonymous tip that Jacob’s childhood best friend, Derek Yoo, posted on Facebook, “Jake, everyone knows you did it. You have a knife. I’ve seen it,’ ” Andy then looks through Jacob’s drawers and finds a folding knife in one of his T-shirts. In the chapter aptly titled “Denial,” Andy, an experienced prosecutor, does not turn the knife over as evidence, but instead disposes of it – believing Jacob that he did not take the knife to school the day his classmate was stabbed.
After Jacob is indicted, Andy Barber confesses to his wife, Laurie, that his estranged father who left when he was 6 is actually in prison convicted of murdering and raping a woman. In the novel, his grandfather and great-grandfather are also convicted felons. Laurie reveals this family history to Jacob’s attorney, and the attorney subsequently refers the family to a forensic psychologist. In the novel, she is a large Jewish woman; in the miniseries she is played by a very thin Poorna Jagannathan (who incidentally has portrayed a therapist in the television series “Sorry for your Loss,” and a doctor in “The Act,” “Better Call Saul,” “NCIS: Los Angeles,” “House of Cards,” “The Game,” “Law and Order: Criminal Intent,” “Rescue Me,” “Jonny Zero,” “An Actor Prepares,” “The Circle,” “Thanks for Sharing,” and “Montclair.”) Although the goal of the defense was a finding of “not guilty,” a psychiatric defense was going to be used as a last resort if necessary.
Laurie had already googled and learned of “the murder gene,” which was further explained by the forensic psychologist as a mutation called:
“MAOA Knockout. It has been argued in court as a trigger for violence before, but the argument was too simplistic, and it was rejected. Our understanding of the gene-environment interplay has improved since then – the science is getting better and very quickly – and we may have better testimony now. The second mutation is located in what’s called the serotonin transporter gene. The official name for the gene is SLC6A4. It’s located on chromosome 17. It encodes a protein that facilitates the activity of the serotonin transporter system, which is what enables the reuptake of serotonin from the synapse back into the neuron.”1
She further explains that there have been many studies on the “nurture” side of the nature/nurture question and that, with new developments in DNA studies, it is now becoming possible to study the “nature” side.
“Defending Jacob” explores the nature/nurture issue, as well as issues with forensic testimony in court and the criminal justice system in general. The issue of repressing feelings and hiding secrets and then having to confront both in a brutal manner is another theme addressed in the story. Andy tried to hide and forget that his father was in prison and the criminal history in his family, but he was forced to face this and his feelings about it when confronted with his own son being accused of murder. Of note, he does not seek help from a therapist despite these life-altering events. (Humongous spoiler alert:) The story that began with a murder of an unrelated child may end with a family murder, one that would be well described and could be understood by psychiatrists using the categories of motives initially described by Phillip Resnick, MD.2
Once again, and unfortunately, as we have pointed out in other media reviews, the portrayal of psychiatric/psychological themes is problematic. Using a psychologist to explain the science of DNA and not a psychiatrist is an interesting choice. Diagnosing a 14-year-old with personality disorders also contributes to misunderstanding and stigma. In addition, no timely attempt is made to refer the accused Jacob for mental health treatment. The stigmatization of psychiatry in the media was addressed by the World Psychiatric Association task force guidance on how to combat stigmatization of psychiatry and psychiatrists,3 including breaking down negative views of psychiatrists and psychiatry in the general public, among medical students, other health professionals, and patients and relatives. The task force made recommendations for national psychiatric societies and for individual practitioners to help reduce stigma of the profession of psychiatry. We would argue that speaking to the media, including fiction authors, to help educate about mental health is an important role for psychiatrists. It would lead to more realistic portrayals in film and books.
Overall, “Defending Jacob” is a compelling story in both the novel and the miniseries. Despite some problems with how it depicts mental health issues, both are engaging and contain thoughtful, extremely well-written themes of interest to many clinical and forensic psychiatrists.
References
1. Landay W. Defending Jacob, a novel. New York: Delacorte Press, 2012.
2. Friedman SH. Family Murder: Pathologies of Love and Hate. Washington: American Psychiatric Association Publishing, 2019.
3. Sartorius N et al. World Psychiatry. 2010 Oct;9(3):131-44.
Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill Cornell Medical Center. Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington: American Psychiatric Association Publishing, 2019), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law and was awarded the 2020 Manfred Gutmacher Award by the American Psychiatric Association.
The 2012 crime fiction novel, “Defending Jacob,” by William Landay was dramatized into a miniseries created by Mark Bomback that premiered on April 24, 2020, on Apple TV+ (and for those resisting a subscription, “The Morning Show” and “Defending Jacob” are both worth it). Both the “Defending Jacob” novel and the miniseries have themes that are of interest to psychiatry, especially to child and forensic psychiatrists, and both the literary and TV versions are excellent, albeit disturbing, diversions from the current pandemic.
(Spoiler alert!) The story is set in the affluent town of Newton, Mass., where crime is generally low and homicides extremely infrequent. Protagonist Andy Barber, a 51-year-old Jewish assistant district attorney, is played by a younger Chris Evans in the miniseries. His wife, Laurie Gold Barber, a 51-year-old Jewish former schoolteacher and stay-at-home mom, is played by a younger Michelle Dockery of Downton Abbey fame. In the miniseries, her character is actively working as a teacher and social activist for children. Other differences between the novel and the miniseries will be pointed out when relevant, but the overall narrative is similar. Both stories are cleverly told through Andy Barber speaking in retrospect as he is being questioned in front of a grand jury for a potential indictment.
When 14-year-old Ben Rifkin is found stabbed to death in Cold Spring Park before school one morning, Andy Barber initially takes the case despite his boss’s reservations that there may be a conflict because Andy’s son Jacob is a student in Ben’s class at school. As the title suggests, it soon becomes clear that Jacob may have had something to do with the murder. At that point, Andy is taken off the case and it is given to a junior colleague, Neal Logiudice, who demonstrates both admiration and contempt for his former mentor, perhaps because of underlying jealousy and insecurity. Neal Logiudice becomes the DA questioning Andy Barber.
Prior to Jacob’s formal accusation of murder, the Barbers appear to be fiercely loyal and unable to fully see and understand their son. The difficulty with objectivity and the reasons why family member physicians should never treat family members – and why family member attorneys should never represent loved ones – is abundantly clear in this story. When Andy receives an anonymous tip that Jacob’s childhood best friend, Derek Yoo, posted on Facebook, “Jake, everyone knows you did it. You have a knife. I’ve seen it,’ ” Andy then looks through Jacob’s drawers and finds a folding knife in one of his T-shirts. In the chapter aptly titled “Denial,” Andy, an experienced prosecutor, does not turn the knife over as evidence, but instead disposes of it – believing Jacob that he did not take the knife to school the day his classmate was stabbed.
After Jacob is indicted, Andy Barber confesses to his wife, Laurie, that his estranged father who left when he was 6 is actually in prison convicted of murdering and raping a woman. In the novel, his grandfather and great-grandfather are also convicted felons. Laurie reveals this family history to Jacob’s attorney, and the attorney subsequently refers the family to a forensic psychologist. In the novel, she is a large Jewish woman; in the miniseries she is played by a very thin Poorna Jagannathan (who incidentally has portrayed a therapist in the television series “Sorry for your Loss,” and a doctor in “The Act,” “Better Call Saul,” “NCIS: Los Angeles,” “House of Cards,” “The Game,” “Law and Order: Criminal Intent,” “Rescue Me,” “Jonny Zero,” “An Actor Prepares,” “The Circle,” “Thanks for Sharing,” and “Montclair.”) Although the goal of the defense was a finding of “not guilty,” a psychiatric defense was going to be used as a last resort if necessary.
Laurie had already googled and learned of “the murder gene,” which was further explained by the forensic psychologist as a mutation called:
“MAOA Knockout. It has been argued in court as a trigger for violence before, but the argument was too simplistic, and it was rejected. Our understanding of the gene-environment interplay has improved since then – the science is getting better and very quickly – and we may have better testimony now. The second mutation is located in what’s called the serotonin transporter gene. The official name for the gene is SLC6A4. It’s located on chromosome 17. It encodes a protein that facilitates the activity of the serotonin transporter system, which is what enables the reuptake of serotonin from the synapse back into the neuron.”1
She further explains that there have been many studies on the “nurture” side of the nature/nurture question and that, with new developments in DNA studies, it is now becoming possible to study the “nature” side.
“Defending Jacob” explores the nature/nurture issue, as well as issues with forensic testimony in court and the criminal justice system in general. The issue of repressing feelings and hiding secrets and then having to confront both in a brutal manner is another theme addressed in the story. Andy tried to hide and forget that his father was in prison and the criminal history in his family, but he was forced to face this and his feelings about it when confronted with his own son being accused of murder. Of note, he does not seek help from a therapist despite these life-altering events. (Humongous spoiler alert:) The story that began with a murder of an unrelated child may end with a family murder, one that would be well described and could be understood by psychiatrists using the categories of motives initially described by Phillip Resnick, MD.2
Once again, and unfortunately, as we have pointed out in other media reviews, the portrayal of psychiatric/psychological themes is problematic. Using a psychologist to explain the science of DNA and not a psychiatrist is an interesting choice. Diagnosing a 14-year-old with personality disorders also contributes to misunderstanding and stigma. In addition, no timely attempt is made to refer the accused Jacob for mental health treatment. The stigmatization of psychiatry in the media was addressed by the World Psychiatric Association task force guidance on how to combat stigmatization of psychiatry and psychiatrists,3 including breaking down negative views of psychiatrists and psychiatry in the general public, among medical students, other health professionals, and patients and relatives. The task force made recommendations for national psychiatric societies and for individual practitioners to help reduce stigma of the profession of psychiatry. We would argue that speaking to the media, including fiction authors, to help educate about mental health is an important role for psychiatrists. It would lead to more realistic portrayals in film and books.
Overall, “Defending Jacob” is a compelling story in both the novel and the miniseries. Despite some problems with how it depicts mental health issues, both are engaging and contain thoughtful, extremely well-written themes of interest to many clinical and forensic psychiatrists.
References
1. Landay W. Defending Jacob, a novel. New York: Delacorte Press, 2012.
2. Friedman SH. Family Murder: Pathologies of Love and Hate. Washington: American Psychiatric Association Publishing, 2019.
3. Sartorius N et al. World Psychiatry. 2010 Oct;9(3):131-44.
Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill Cornell Medical Center. Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington: American Psychiatric Association Publishing, 2019), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law and was awarded the 2020 Manfred Gutmacher Award by the American Psychiatric Association.
The 2012 crime fiction novel, “Defending Jacob,” by William Landay was dramatized into a miniseries created by Mark Bomback that premiered on April 24, 2020, on Apple TV+ (and for those resisting a subscription, “The Morning Show” and “Defending Jacob” are both worth it). Both the “Defending Jacob” novel and the miniseries have themes that are of interest to psychiatry, especially to child and forensic psychiatrists, and both the literary and TV versions are excellent, albeit disturbing, diversions from the current pandemic.
(Spoiler alert!) The story is set in the affluent town of Newton, Mass., where crime is generally low and homicides extremely infrequent. Protagonist Andy Barber, a 51-year-old Jewish assistant district attorney, is played by a younger Chris Evans in the miniseries. His wife, Laurie Gold Barber, a 51-year-old Jewish former schoolteacher and stay-at-home mom, is played by a younger Michelle Dockery of Downton Abbey fame. In the miniseries, her character is actively working as a teacher and social activist for children. Other differences between the novel and the miniseries will be pointed out when relevant, but the overall narrative is similar. Both stories are cleverly told through Andy Barber speaking in retrospect as he is being questioned in front of a grand jury for a potential indictment.
When 14-year-old Ben Rifkin is found stabbed to death in Cold Spring Park before school one morning, Andy Barber initially takes the case despite his boss’s reservations that there may be a conflict because Andy’s son Jacob is a student in Ben’s class at school. As the title suggests, it soon becomes clear that Jacob may have had something to do with the murder. At that point, Andy is taken off the case and it is given to a junior colleague, Neal Logiudice, who demonstrates both admiration and contempt for his former mentor, perhaps because of underlying jealousy and insecurity. Neal Logiudice becomes the DA questioning Andy Barber.
Prior to Jacob’s formal accusation of murder, the Barbers appear to be fiercely loyal and unable to fully see and understand their son. The difficulty with objectivity and the reasons why family member physicians should never treat family members – and why family member attorneys should never represent loved ones – is abundantly clear in this story. When Andy receives an anonymous tip that Jacob’s childhood best friend, Derek Yoo, posted on Facebook, “Jake, everyone knows you did it. You have a knife. I’ve seen it,’ ” Andy then looks through Jacob’s drawers and finds a folding knife in one of his T-shirts. In the chapter aptly titled “Denial,” Andy, an experienced prosecutor, does not turn the knife over as evidence, but instead disposes of it – believing Jacob that he did not take the knife to school the day his classmate was stabbed.
After Jacob is indicted, Andy Barber confesses to his wife, Laurie, that his estranged father who left when he was 6 is actually in prison convicted of murdering and raping a woman. In the novel, his grandfather and great-grandfather are also convicted felons. Laurie reveals this family history to Jacob’s attorney, and the attorney subsequently refers the family to a forensic psychologist. In the novel, she is a large Jewish woman; in the miniseries she is played by a very thin Poorna Jagannathan (who incidentally has portrayed a therapist in the television series “Sorry for your Loss,” and a doctor in “The Act,” “Better Call Saul,” “NCIS: Los Angeles,” “House of Cards,” “The Game,” “Law and Order: Criminal Intent,” “Rescue Me,” “Jonny Zero,” “An Actor Prepares,” “The Circle,” “Thanks for Sharing,” and “Montclair.”) Although the goal of the defense was a finding of “not guilty,” a psychiatric defense was going to be used as a last resort if necessary.
Laurie had already googled and learned of “the murder gene,” which was further explained by the forensic psychologist as a mutation called:
“MAOA Knockout. It has been argued in court as a trigger for violence before, but the argument was too simplistic, and it was rejected. Our understanding of the gene-environment interplay has improved since then – the science is getting better and very quickly – and we may have better testimony now. The second mutation is located in what’s called the serotonin transporter gene. The official name for the gene is SLC6A4. It’s located on chromosome 17. It encodes a protein that facilitates the activity of the serotonin transporter system, which is what enables the reuptake of serotonin from the synapse back into the neuron.”1
She further explains that there have been many studies on the “nurture” side of the nature/nurture question and that, with new developments in DNA studies, it is now becoming possible to study the “nature” side.
“Defending Jacob” explores the nature/nurture issue, as well as issues with forensic testimony in court and the criminal justice system in general. The issue of repressing feelings and hiding secrets and then having to confront both in a brutal manner is another theme addressed in the story. Andy tried to hide and forget that his father was in prison and the criminal history in his family, but he was forced to face this and his feelings about it when confronted with his own son being accused of murder. Of note, he does not seek help from a therapist despite these life-altering events. (Humongous spoiler alert:) The story that began with a murder of an unrelated child may end with a family murder, one that would be well described and could be understood by psychiatrists using the categories of motives initially described by Phillip Resnick, MD.2
Once again, and unfortunately, as we have pointed out in other media reviews, the portrayal of psychiatric/psychological themes is problematic. Using a psychologist to explain the science of DNA and not a psychiatrist is an interesting choice. Diagnosing a 14-year-old with personality disorders also contributes to misunderstanding and stigma. In addition, no timely attempt is made to refer the accused Jacob for mental health treatment. The stigmatization of psychiatry in the media was addressed by the World Psychiatric Association task force guidance on how to combat stigmatization of psychiatry and psychiatrists,3 including breaking down negative views of psychiatrists and psychiatry in the general public, among medical students, other health professionals, and patients and relatives. The task force made recommendations for national psychiatric societies and for individual practitioners to help reduce stigma of the profession of psychiatry. We would argue that speaking to the media, including fiction authors, to help educate about mental health is an important role for psychiatrists. It would lead to more realistic portrayals in film and books.
Overall, “Defending Jacob” is a compelling story in both the novel and the miniseries. Despite some problems with how it depicts mental health issues, both are engaging and contain thoughtful, extremely well-written themes of interest to many clinical and forensic psychiatrists.
References
1. Landay W. Defending Jacob, a novel. New York: Delacorte Press, 2012.
2. Friedman SH. Family Murder: Pathologies of Love and Hate. Washington: American Psychiatric Association Publishing, 2019.
3. Sartorius N et al. World Psychiatry. 2010 Oct;9(3):131-44.
Dr. Rosenbaum is a clinical and forensic psychiatrist in private practice in New York. She is an assistant clinical professor at New York University Langone Medical Center and on the faculty at Weill Cornell Medical Center. Dr. Hatters Friedman serves as the Phillip Resnick Professor of Forensic Psychiatry at Case Western Reserve University, Cleveland. She is also editor of Family Murder: Pathologies of Love and Hate (Washington: American Psychiatric Association Publishing, 2019), which was written by the Group for the Advancement of Psychiatry’s Committee on Psychiatry & Law and was awarded the 2020 Manfred Gutmacher Award by the American Psychiatric Association.