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Top AGA Community patient cases
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)
• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)
• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)
• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)
• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)
• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)
Roundtables (https://community.gastro.org/discussions/)
• GI COVID-19 Connection: Work-life balance in the COVID era.
• Trainee & early career networking connection.
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)
• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)
• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)
• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)
• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)
• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)
Roundtables (https://community.gastro.org/discussions/)
• GI COVID-19 Connection: Work-life balance in the COVID era.
• Trainee & early career networking connection.
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.
In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:
• Patient case: Elevated aminotransferases of unknown origin. (https://community.gastro.org/posts/21890)
• Patient case: Functional bowel obstruction. (https://community.gastro.org/posts/21888)
• Patient case: Autoimmune hepatitis with chronic hepatitis C. (https://community.gastro.org/posts/21880)
• Patient case: Immunosuppression in IBD (https://community.gastro.org/posts/21860)
• Is COVID-19 reinfection fact or fiction? (https://community.gastro.org/posts/21824)
• Experience with HALO procedures in ambulatory surgery centers. (https://community.gastro.org/posts/21812)
Roundtables (https://community.gastro.org/discussions/)
• GI COVID-19 Connection: Work-life balance in the COVID era.
• Trainee & early career networking connection.
View all upcoming Roundtables in the community at https://community.gastro.org/discussions.
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
Bisphosphonates may have limited ‘protective’ effect against knee OA progression
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
New data from the National Institutes of Health–funded Osteoarthritis Initiative suggest that, in some women at least, taking bisphosphonates may help to reduce the chances that there will be radiographic progression of knee osteoarthritis (OA).
In a propensity-matched cohort analysis, women who had a Kellgren and Lawrence (KL) grade of less than 2 and who used bisphosphonates were half as likely as those who did not use bisphosphonates to have radiographic OA progression at 2 years (hazard ratio, 0.53; 95% confidence interval, 0.35-0.79). Radiographic OA progression has been defined as a one-step increase in the KL grade.
While the association appeared even stronger in women with a KL grade less than 2 and who were not overweight (HR, 0.49; 95% CI, 0.26-0.92), bisphosphonate use was not associated with radiographic OA progression in women with a higher (≥2) KL grade (HR, 1.06; 95% CI, 0.83-1.35).
“In all analyses, the effect of bisphosphonates was larger in radiographic-disease-naive individuals, suggesting protection using bisphosphonates may be more profound in those who do not already have evidence of knee damage or who have mild disease, and once damage occurs, bisphosphonate use may not have much effect,” Kaleen N. Hayes, PharmD, of the University of Toronto and her coauthors reported in the Journal of Bone and Mineral Research.
“Our study was the first to our knowledge to examine bisphosphonate exposure effects in different disease severity subgroups and obesity classifications using a rigorous, propensity-matched time-to-event analysis that uniquely addresses confounding by indication,” Dr. Hayes and her team wrote.
Furthermore, they noted that extensive sensitivity analyses, which included redoing the primary analyses to look at statin use, showed that their main conclusions were unchanged and that this helped account for any potential residual confounding, healthy-user bias, or exposure misclassification.
Study details
The Osteoarthritis Initiative is a 10-year longitudinal cohort study conducted at four clinical sites in the United States and recruited men and women aged 45-75 years over a 2-year period starting in 2004. Dr. Hayes and her coauthors restricted their analyses to women 50 years and older. Their study population consisted of 344 bisphosphonate users and 344 bisphosphonate nonusers.
The main bisphosphonate being taken was alendronate (69%), and the average duration of bisphosphonate use was 3.3 years, but no significant effect of duration of use on radiographic progression was found.
The women were followed until the first radiographic OA progression, or the first missed visit or end of the 2-year follow-up period.
Overall, 95 (13.8%) of the 688 women included in the analysis experienced radiographic OA progression. Of those, 27 (3.9%) had a KL grade of less than 2 and 68 (9.8%) had a KL grade of 2 or greater. Ten women with KL less than 2 and 27 women with KL or 2 or greater were taking bisphosphonates at their baseline visit.
“Kaplan-Meier analysis indicated that non-users and users with a baseline KL grade of 0 or 1 had 2-year risks of progression of 10.5% and 5.9%, respectively, whereas non-users and users with a baseline KL grade of 2 or 3 had 2-year of these women risks of progression of 23.0% and 23.5%, respectively,” reported the authors.
Before propensity score matching, Dr. Hayes and her colleagues observed that women taking bisphosphonates were older, had lower body weight and a higher prevalence of any fracture or hip and vertebral fractures, and were also more likely be White, compared with non-users. “In addition, bisphosphonate-users appeared to be healthier than non-users, as suggested by a lower smoking prevalence, lower average baseline KL grade, lower diabetes prevalence, and higher multivitamin use (a healthy-user proxy),” they acknowledged.
Results in perspective
“The key thing that I’m concerned about when I see something like bisphosphonates and osteoarthritis is just how well confounding has been addressed,” commented Tuhina Neogi, MD, PhD, professor of medicine and epidemiology at Boston University and chief of rheumatology at Boston Medical Center, in an interview.
“So are there factors other than the bisphosphonates themselves that might explain the findings? It looks like they’ve taken into account a lot of important things that one would consider for trying to get the two groups to look as similar as possible,” she added. Dr. Neogi queried, however, if body mass index had been suitably been adjusted for even after propensity score matching.
“The effect estimate is quite large, so I do think there is some confounding. So I would feel comfortable saying that there’s a signal here for bisphosphonates in reducing the risk of progression among those who do not have radiographic OA at baseline,” Dr. Neogi observed.
“The context of all this is that there have been large, well-designed, randomized control trials of oral bisphosphonates from years ago that did not find any benefit of bisphosphonates in [terms of] radiographic OA progression,” Dr. Neogi explained.
In the Knee OA Structural Arthritis (KOSTAR) study, now considered “quite a large landmark study,” the efficacy of risedronate in providing symptom relief and slowing disease progression was studied in almost 2,500 patients. “They saw some improvements in signs and symptoms, but risedronate did not significantly reduce radiographic progression. [However] there were some signals on biomarkers,” Dr. Neogi said.
One of the issues is that radiographs are too insensitive to pick up early bone changes in OA, a fact not missed by Dr. Hayes et al. More recent research has thus looked to using more sensitive imaging methods, such as CT and MRI, such as a recent study published in JAMA looking at the use of intravenous zoledronic acid on bone marrow lesions and cartilage volume. The results did not show any benefit of bisphosphonate use over 2 years.
“So even though we thought the MRI might provide a better way to detect a signal, it hasn’t panned out,” Dr. Neogi said.
But that’s not to say that there isn’t still a signal. Dr. Neogi’s most recent research has been using MRI to look at bone marrow lesion volume in women who were newly starting bisphosphonate therapy versus those who were not, and this has been just been accepted for publication.
“We found no difference in bone marrow lesion volume between the two groups. But in the women who had bone marrow lesions at baseline, there was a statistically significant greater proportion of women on bisphosphonates having a decrease in bone marrow lesion volume than the non-initiators,” she said.
So is there evidence that putting more women on bisphosphonates could prevent OA? “I’m not sure that you would be able to say that this should be something that all postmenopausal women should be on,” Dr. Neogi said.
“There’s a theoretical risk that has not been formally studied that, if you diminish bone turnover and you get more and more mineralization occurring, the bone potentially may have altered mechanical properties, become stiffer and, over the long term, that might not be good for OA.”
She added that, if there is already a clear clinical indication for bisphosphonate use, however, such as older women who have had a fracture and who should be on a bisphosphonate anyway, then “a bisphosphonate has the theoretical potential additional benefit for their osteoarthritis.”
The authors and Dr. Neogi had no conflicts of interest or relationships to disclose.
SOURCE: Hayes KN et al. J Bone Miner Res. 2020 July 14. doi: 10.1002/jbmr.4133.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
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.
Ixekizumab deemed effective for pityriasis rubra pilaris
Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.
The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.
PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.
Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.
The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.
Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.
The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.
The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.
To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.
No serious or unexpected adverse events occurred in the 24-week study.
“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.
Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.
“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.
Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.
“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.
She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.
Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.
Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.
The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.
PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.
Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.
The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.
Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.
The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.
The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.
To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.
No serious or unexpected adverse events occurred in the 24-week study.
“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.
Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.
“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.
Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.
“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.
She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.
Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.
Teri Greiling, MD, PhD, said at the virtual annual meeting of the American Academy of Dermatology.
The interleukin-17A inhibitor induced long-term remission of pityriasis rubra pilaris (PRP) in 4 of the 11 participants in her open-label, single-arm, 24-week clinical trial of ixekizumab (Taltz) at the Food and Drug Administration–approved dosing for psoriasis. Of 11 patients, 7 experienced at least a 50% reduction in signs and symptoms of the disease. Marked quality-of-life improvements occurred as well, reported Dr. Greiling, a dermatologist at Oregon Health & Science University, Portland.
PRP is a rare papulosquamous disorder that’s challenging to diagnosis and often difficult to treat. Indeed, there is no FDA-approved treatment. The disorder is characterized by widespread follicular keratotic plaques with scale and notable islands of sparing, often with an accompanying waxy yellow palmoplantar keratoderma with fissuring. There are adult- and childhood-onset forms of PRP, as well as sporadic and familial subtypes. Some cases are associated with variants in the CARD14 gene, known to also play a role in familial psoriasis.
Patients with PRP say the disorder has a major adverse impact on their quality of life. Itching and pain are often prominent features.
The 11 study participants, drawn from throughout the United States, were adults with a mean 12-year history of symptoms. All were required to have both clinical and biopsy evidence of PRP. Five had classic adult-onset PRP, five had atypical adult-onset PRP, and one had classic juvenile-onset PRP. All had moderate or severe disease as reflected in a Physician’s Global Assessment score of 3 or 4 on the 0-4 scale. Of the 11, 10 had previously received various systemic therapies for their PRP without success.
Since there is as yet no established PRP severity grading tool, Dr. Greiling applied the principles of the Psoriasis Area and Severity Index (PASI). Participants had a mean baseline PASI score of 24.6, a Dermatology Life Quality Index (DLQI) score of 18, and itch and pain scores of 7 and 6, respectively, on a self-rated 10-point scale.
The primary outcome in the study was change in PASI score at week 24, which was 4 weeks after the final dose of ixekizumab. The mean score improved from 24.8 at week 0 to 9.7 at week 24. Five patients achieved at least a 75% decrease in PASI score, or PASI 75 response, and 2 had a PASI 90 response. The DLQI improved from 18 to 3, and both itch and pain scores dropped to a median of 1. There was no association between response to treatment and PRP clinical subtype.
The four top responders – those with a PASI 89 or better response at week 24 – remained clear or almost clear at week 36, fully 16 weeks after their last dose of ixekizumab. Patients with an intermediate week 24 response – that is, a 50%-85% reduction in PASI score – all relapsed before week 36. The patient with the worst PASI score at both baseline and 24 weeks decided to continue on ixekizumab dosed every 2 weeks independent of the study, rather than at the FDA-approved dosing every 4 weeks for psoriasis, with a resultant drop to a PASI score of 8 at week 36.
To look at mechanism of benefit, Dr. Greiling used quantitative polymerase chain reaction to examine key cytokine expression in the epidermis and dermis. Not surprisingly, IL-17A expression was markedly reduced at both sites, suggesting the importance of the Th17 axis in the pathophysiology of PRP. In contrast, there was no significant change in IL-23 expression.
No serious or unexpected adverse events occurred in the 24-week study.
“In terms of ixekizumab, compared to other treatments, I definitely think it is more effective than any conventional therapies, such as topical steroids, methotrexate, or acitretin,” she said in an interview.
Asked about other biologics, Dr. Greiling said she hasn’t found tumor necrosis factor inhibitors very helpful in her patients with PRP. A formal trial of the IL-17A inhibitor secukinumab (Cosentyx) has been done elsewhere, and although the results haven’t yet been published, her understanding is that the efficacy was similar to her ixekizumab trial.
“I’ve had some of my ixekizumab patients switch to secukinumab, for insurance reasons, though, and had it not be quite as effective, although still helpful,” she said.
Dr. Greiling is now enrolling patients with PRP in a trial of the IL-23 inhibitor guselkumab (Tremfya). It’s her early impression that this may prove to be another therapeutic option.
“I have not yet used brodalumab [Siliq], but I wonder if it would also be helpful, since it seems to have a stronger blockade, working on the IL-17 receptor A,” she said.
She cited two pressing needs that would advance PRP research: the lack of standard criteria for disease diagnosis and the absence of PRP-specific disease measurement tools. “We’re trying to remedy that,” the dermatologist said.
Her study was funded by Eli Lilly. She reported receiving research funding from that company and Janssen.
FROM AAD 2020
Intravesical BCG dosing frequency ‘critical’ in bladder cancer
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
The rates of recurrence were 27.1% in the reduced dosing frequency arm and 12% in the standard dosing frequency arm. These results were reported at the virtual annual congress of the European Association of Urology.
More patients in the reduced dosing frequency arm than in the standard dosing frequency arm had a shorter time to recurrence, which was the primary endpoint of the trial.
At 6 months, the rate of recurrence was 18% in the reduced frequency arm and 8% in the standard frequency arm. The gap widened further at both 12 months (24% and 11%, respectively) and 24 months (34% and 15%, respectively). The hazard ratio for time to recurrence was 0.403 in favor of the standard dosing frequency arm.
“The recommended dose and schedule of BCG consists of once-weekly installations during 6 weeks of induction, followed by 3 weeks of maintenance at 3, 6, and 12 months,” observed study investigator Marc-Oliver Grimm, MD, of Jena (Germany) University Hospital.
“BCG instillation is, however, frequently associated with adverse events, which may lead to discontinuation, and several attempts have been made to reduce symptom burden associated with BCG,” he added.
Dr. Grimm presented the recently published findings from NIMBUS (Eur Urol. 2020 May 20;S0302-2838[20]30334-1) alongside some new information from a post hoc analysis.
Trial details
NIMBUS was a randomized, unblinded study of 345 patients with high-grade NMIBC who were recruited over a prolonged period, Dr. Grimm said. The long accrual was caused by a shortage of BCG and meant that the statistical assumptions had to be revised to include fewer patients.
The trial was designed to compare induction consisting of three versus six weekly BCG instillations and maintenance consisting of two versus three weekly BCG instillations at 3, 6, and 12 months. The aim had been to show that a reduced dosing frequency of BCG – 9 rather than 15 instillations – was noninferior to the standard dosing frequency of BCG, Dr. Grimm said. However, that was not the case, and the trial had to be stopped prematurely. In October 2019, the study’s sponsor, the EAU Research Foundation, announced that the trial would end.
Despite its unexpected ending, the trial’s data now fill some knowledge gaps, as pointed out by the discussant for the trial, Peter Black, MD, of the University of British Columbia in Vancouver.
Previous studies, such as the SWOG 8507, EORTC 30962, and CUETO 98013 trials, had shown that maintenance treatment works, but the schedule matters, he said. Results have also shown that the duration of maintenance treatment is less important than the dose of BCG given.
“The NIMBUS trial now tells us that dosing frequency is critical,” Dr. Black said.
Not only did the NIMBUS trial alter the maintenance schedule, it also altered the induction course of BCG instillation.
“The dramatic difference in recurrence-free survival, especially with the large separation of K-M [Kaplan-Meier] curves early on, suggests that this change to induction has had a major impact on the outcomes,” Dr. Black observed.
Post hoc analysis
Dr. Grimm presented a post hoc analysis comparing the rates of recurrence in the NIMBUS trial with rates seen in the EORTC 30962 and CUETO 98013 trials. Dr. Black also compared NIMBUS results to results from the SWOG 8507 trial.
The analysis showed lower rates of recurrence in the standard dose frequency arm in the NIMBUS trial than in the EORTC and CUETO trials at both 12 months (11%, 25%, and 18%, respectively) and 24 months (15%, 32%, and 27%, respectively).
However, as Dr. Black pointed out, the SWOG trial had similar recurrence rates as the NIMBUS trial at 12 months (9% and 11%, respectively) and 24 months (19% and 15%, respectively).
Dr. Grimm suggested that the lower rates of recurrence in the standard dosing arm of NIMBUS versus the other trials might have been because 91% of patients in the NIMBUS trial having undergone repeat transurethral resection for bladder tumor before BCG instillation.
Dr. Black said while this might have had an effect, it was probably not the only answer. While it’s true that the other trials had not considered repeat transurethral resection for bladder tumor, there were other confounding factors that might have been important, from patient selection bias to the use of advanced cystoscopy technologies, he said.
“If we really want to discern differences between surgery and intravesical therapy, we need to focus on CIS [carcinoma in situ] patients. Although this has major implications on feasibility since the patient pool is smaller,” Dr. Black said.
“One final point I’d like to make is that we really need to use these trials to understand the biology of non–muscle invasive bladder cancer,” he said. ”We know that BCG induces a cellular response, and we can measure this, as well as cytokine response. We know that the response builds to a plateau over four to six doses of induction and over two to three doses of maintenance therapy. This is perhaps more rapid in patients with pre-existing BCG immune reactivity. But there is biological rationale for the current six-plus-three protocol, and I think the reduced dose frequency in the NIMBUS trial probably failed to achieve the same immune activation as the established protocol.”
“If we were faced with a BCG shortage, it is better to reduce dose or duration of therapy but not the frequency of dosing,” Dr. Black added.
The NIMBUS trial was sponsored by the EAU Research Foundation. Dr. Grimm disclosed ties to Novartis, Bristol-Myers Squibb, Pfizer, AstraZeneca, and many other pharmaceutical companies. Dr. Black had no conflicts of interests relevant to his comments.
SOURCE: Grimm M-O. EAU20. https://urosource.uroweb.org/resource-centre/EAU20V/212877/Abstract/
FROM EAU20
Do chocolate lovers have healthier arteries?
Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.
Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.
The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.
Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.
The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.
“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.
The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.
Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.
However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.
Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.
Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.
The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.
Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.
The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.
“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.
The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.
Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.
However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.
Adults who ate chocolate more than once a week or more than 3.5 times a month were significantly less likely to develop coronary artery disease than were those who ate less chocolate, according to data from a meta-analysis of more than 300,000 individuals.
Consumption of chocolate has shown beneficial effects on blood pressure and endothelial function, wrote Chayakrit Krittanawong, MD, of Baylor College of Medicine, Houston, and colleagues in the European Journal of Preventive Cardiology. “However, the potential benefit of increased chocolate consumption reducing coronary artery disease (CAD) risk is not known,” they said.
The investigators reviewed data from 5 decades of research, including six studies with a total of 336,289 individuals who reported chocolate consumption. The study participants experienced 14,043 cases of CAD, 4,667 myocardial infarctions, 2,735 cerebrovascular accidents, and 332 cases of heart failure over an average follow-up period of 8.78 years.
Overall, higher chocolate consumption (defined as more than once a week or more than 3.5 times a month) was significantly associated with a decreased CAD risk (pooled risk ratio, 0.94; P < .001) compared to eating no chocolate or eating chocolate less than once a week.
The cardioprotective effects of chocolate may be linked to several nutrients, the researchers noted. Chocolate’s flavenols (epicatechin, catechin, and procyanidins) have demonstrated an ability to reduce myocardial infarct size in an animal study and to reduce platelet aggregation and improve endothelial function in humans with and without CAD. In addition, methylxanthines have demonstrated beneficial effects on cardiovascular function, polyphenols have been shown to facilitate nitric oxide synthesis, and stearic acid has been associated with reduced mean platelet volume, they wrote.
“The benefits of nutrients in chocolate appear promising and chocolate consumption at least once a week may be beneficial for CAD prevention,” the researchers suggested, although they cautioned that the effects of supplemental calories and the impact of fats, milk, and sugar in commercial chocolate must be taken into account.
The study findings were limited by several factors, including the potential dietary confounders such as total energy intake and the type of chocolate consumed (milk, dark, or white) and the relatively homogeneous study population, which included mainly individuals from Europe and the United States.
Additional long-term, double-blind, randomized trials are needed to identify the cardioprotective effects of chocolate, and “studies to determine the role of genetic potential and the beneficial effects of chocolate on CAD may be needed,” the researchers noted.
However, the current study results suggest that “consumption of chocolates at least once a week is associated with a reduction in the risk of CAD,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Krittanawong C et al. Eur J Prev Cardiol. 2020 Jul 23. doi: 10.1177/2047487320936787.
FROM THE EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
Learn to anticipate, resolve difficult interactions with patients
Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.
Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.
Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.
To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.
“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.
Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.
Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.
The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”
Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.
One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).
There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.
However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship.
Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.
Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.
Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.
Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.
To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.
“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.
Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.
Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.
The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”
Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.
One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).
There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.
However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship.
Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.
Every physician encounters difficult or challenging patients during their career, but learning how to anticipate and handle these interactions is not something taught in medical school or residency, according to Donald W. Black, MD, MS.
Difficult or challenging encounters with patients are not only unavoidable, they should be expected, Dr. Black said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Every doctor I know has had challenging interactions,” he said. About 15% of encounters were deemed “difficult” in a prospective study of patients by Jeffrey L. Jackson, MD, MPH, and Kurt Kroenke, MD. A depressive or anxiety disorder was present in 29% of patients, with 11% experiencing two or more disorders. Major depression was present in 8.4%, other depressive disorders in 17.4%, panic disorder in 1.4%, and other anxiety disorders in 14.2% of patients. Dr. Jackson and Dr. Kroenke found that difficult patients demonstrated disrespect and anger, made threats, and locked themselves in rooms (Arch Intern Med. 1999 May 24;159[10]:1069-75). “Rest assured, you are not the only psychiatrist to face this type of issue,” Dr. Black said at the meeting, presented by Global Academy for Medical Education.
Common scenarios can include patients who want certain tests performed after researching symptoms online, threats of legal or social media action after feeling like they are not being listened to, a demand for a second opinion after not agreeing with a physician’s diagnosis, mistrust of doctors after presenting with symptoms and not being diagnosed, patients who focus on negative outcomes, and those who do not comply with treatment. These patients can often appear angry, defensive, frightened or resistant, or manipulative; may provide vague or exaggerated symptoms; or may inappropriately rely on hospital or clinic staff for emotional and physical support.
To complicate matters, the patients’ condition also might contribute to difficult interactions, such as in patients who have conditions like chronic pain or fibromyalgia.
“These often contribute because patients never feel that their problems are being appropriately addressed,” said Dr. Black, professor of psychiatry at the University of Iowa in Iowa City. Patients with psychiatric disorders can also present unique challenges that may result in difficult encounters. Patients with anxiety might not be able to be reassured by their doctor, for example, or patients with eating disorders might refuse treatment recommendations, he said.
Difficult encounters can lead to physicians feeling angry, upset, stressed, disrespected, abused, or fearful. But “it’s not just about the patient,” Dr. Black said. Physicians can become angry or defensive because of burnout, stress, or frustration, which can lead to them snapping at patients. Physicians are also overworked, sleep-deprived, and busier than they’d like to be, he added. Personal problems can contribute, and a physician’s belief system can cause a bad interaction with a patient. If physicians “label” one of their patients, that might end up becoming a “self-fulfilling prophecy” for that patient, Dr. Black said. Poor communication, such as not conveying bad news appropriately or with empathy, seeing a patient but never making eye contact, and using medical jargon that could be confusing to the patient, also can contribute to a challenging encounter, he added.
Situational issues also might create a bad experience for the patient. For example, a patient might find it hard to make an appointment, or the clinic might be busy or have a lack of privacy or encounter administrative issues. For patients who do not speak English as their native language, not having access to an interpreter can lead to frustration on the part of both the physician and the patient. “Bad interactions are not good for patient care,” Dr. Black said.
The key to resolving these issues is to focus on the goal, Dr. Black said. “We all want the same thing. We want to help the patient get better; we want to keep patients healthy; we want to keep them happy; we want to be fulfilled; [and] we want to manage our time and make a living – and meet our professional expectations.”
Begin by recognizing the difficult situation and assessing how the patient, the environment, or you might be contributing to the problem. “You have to step back and say what’s going on with this, and what are the factors that are combining to create this situation,” Dr. Black said. It is important to be calm and professional and not argue or talk over the patient. The goal is to work with the patient to find a solution.
One technique is to verbalize the problem without blaming the patient, the physician, or the environment (“We both have very different views about how your symptoms should be investigated, and that’s causing some difficulty between us. Do you agree?”).
There also might be alternative explanations for a patient’s behavior. For example, anger could be misdirected at a physician because of anxiety surrounding an unrelated event. In this case, it is important to listen to the patient and empathize, which will help the patient feel supported and build a rapport that can aid in resolving the problem encounter, Dr. Black said. Finding common ground when patients and physicians have different ideas on treatment or diagnosis is another way to help resolve a difficult encounter.
However, setting boundaries also is important, he noted. If, after remediation or if patients demonstrate signs of threatening or abusive behavior, initiate sexual advances, refuse to follow a treatment plan, fail to pay their bills, or are potentially putting themselves in harm’s way through noncompliance, a physician might consider terminating the relationship. Terminating the patient relationship should be done after attempting to work with the patient through a case manager and team members, and clearly advising a patient about behavior that could lead to termination of the patient-provider relationship.
Global Academy and this news organization are owned by the same parent company. Dr. Black reported that he is a consultant for Otsuka and receives royalties from American Psychiatric Publishing, Oxford University Press, and UpToDate. In addition, he receives funding from Nellie Ball Trust, the National Institute on Drug Abuse, the National Institute on Aging, and the National Center for Responsible Gaming.
FROM CP/AACP PSYCHIATRY UPDATE
Experts call for immediate suspension of ECT, others push back
Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.
A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.
However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.
“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”
On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.
“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.
The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
Widespread use
ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.
The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.
In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.
“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”
For Read, the decision to analyze the current state of ECT research was both personal and professional.
“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.
“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.
Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
Ongoing debate
A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.
However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.
For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.
Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.
The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.
The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.
This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:
- Janicak et al, 1985
- Kho, van Vreewijk, Simpson, & Zwinderman, 2003
- Mutz et al, 2019
- Pagnin, de Queiroz, Pini, & Cassano, 2004
- UK ECT Review Group, 2003
The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).
Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.
The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.
What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).
The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”
These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.
Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:
- The short- and long-term efficacy benefits of ECT over SECT;
- Whether ECT is effective among patients who have failed other treatments for depression;
- Whether ECT prevents ;
- Whether ECT improves patients’ quality of life;
- Whether ECT is more effective in women than men;
- Whether ECT is effective in children or adolescents.
“Shoddy” research
The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.
“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.
“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”
Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.
“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.
The authors call for an immediate suspension of ECT until new studies address these research shortcomings.
“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.
“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.
He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
A “lifesaver”
No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.
It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review
“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”
The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.
“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
FDA’s position
Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.
“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”
The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.
Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”
Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”
The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”
As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.
“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”
Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said,
Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.
“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”
Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.
“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
A growing movement
Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.
A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.
“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.
Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.
Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”
Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”
George agreed that the therapy is not without its shortcomings.
“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.
“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.
He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.
“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”
The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.
This article first appeared on Medscape.com.
Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.
A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.
However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.
“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”
On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.
“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.
The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
Widespread use
ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.
The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.
In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.
“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”
For Read, the decision to analyze the current state of ECT research was both personal and professional.
“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.
“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.
Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
Ongoing debate
A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.
However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.
For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.
Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.
The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.
The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.
This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:
- Janicak et al, 1985
- Kho, van Vreewijk, Simpson, & Zwinderman, 2003
- Mutz et al, 2019
- Pagnin, de Queiroz, Pini, & Cassano, 2004
- UK ECT Review Group, 2003
The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).
Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.
The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.
What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).
The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”
These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.
Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:
- The short- and long-term efficacy benefits of ECT over SECT;
- Whether ECT is effective among patients who have failed other treatments for depression;
- Whether ECT prevents ;
- Whether ECT improves patients’ quality of life;
- Whether ECT is more effective in women than men;
- Whether ECT is effective in children or adolescents.
“Shoddy” research
The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.
“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.
“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”
Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.
“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.
The authors call for an immediate suspension of ECT until new studies address these research shortcomings.
“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.
“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.
He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
A “lifesaver”
No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.
It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review
“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”
The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.
“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
FDA’s position
Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.
“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”
The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.
Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”
Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”
The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”
As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.
“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”
Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said,
Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.
“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”
Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.
“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
A growing movement
Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.
A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.
“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.
Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.
Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”
Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”
George agreed that the therapy is not without its shortcomings.
“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.
“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.
He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.
“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”
The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.
This article first appeared on Medscape.com.
Experts are calling for the immediate suspension of electroconvulsive therapy (ECT) for major depression.
A new review by investigators led by John Read, PhD, University of East London, conclude there is no evidence to show that ECT is effective in either its target demographic or its target diagnostic group. They say its use should be suspended until more robust research proves it is safe and effective.
However, the review’s conclusions have been met with passionate opposition from expert psychiatrists who say ECT can be a lifesaving treatment for patients, many of whom have exhausted all other treatment options. Other clinicians maintain that the review itself is fraught with methodologic shortcomings that invalidate its conclusions.
“We’ve concluded there is no adequate research on which to base an answer to the question, ‘Does ECT work?,’ ” Read told Medscape Medical News. “We’re not actually saying ECT doesn’t work. We’re saying there’s no way to know whether it works or not on the basis of the current research, which, after 80 years of the treatment being used, is pretty amazing.”
On the other hand, Read said there is substantial evidence to suggest ECT causes significant adverse events. “Depending who you ask, the psychiatrists or the patients, somewhere between 12% and 55% of patients get permanent or persistent memory loss,” he said.
“So there is a very serious cost to its use, and if there’s a serious cost, you ... have to know that there’s a very strong efficacy benefit, and we just don’t know that. That’s why we’re calling for suspension until there is adequate research,” Read added.
The study was published in a recent issue of Ethical Human Psychology and Psychiatry.
Widespread use
ECT remains a popular treatment modality for resistant depression. Global data show that it is used to treat almost a million patients every year. Although ECT continues to be the subject of comparative research, the investigators say that most of these studies do not adhere to the same standards that govern clinical trials of other psychiatric medications and medical interventions.
The investigators also note that to date, only 11 placebo-controlled studies of the efficacy of ECT have been conducted. They write that the last study to compare ECT with sham or simulated ECT (SECT) – in which a general anesthetic was administered but the electricity was not – was performed in 1985. Nevertheless, this relatively small body of evidence has been the basis of many meta-analyses.
In the current review, the authors evaluated the impartiality and robustness of these previous meta-analyses and the quality of the studies that were included.
“The primary goal is not to assess whether or not ECT is effective,” they write. “The intent, instead, is to determine whether the available evidence is robust enough to answer that question.”
For Read, the decision to analyze the current state of ECT research was both personal and professional.
“As a young nursing attendant in a Bronx hospital, I had the job of sitting with people as they came around from ECT. It was my job to try to explain why they didn’t know who they were, where they were, why their head was throbbing, and why people would do something like that to them,” he said.
“On the research side, this is my sixth review, and in each one we’ve reached the same conclusion,” Read added.
Other research stands in direct opposition to the current review’s findings. Many studies have concluded that ECT is safe and effective for patients with depression.
Ongoing debate
A 2018 registry analysis showed no additional risk for cognitive impairment in patients who underwent ECT up to 40 years after therapy. A 2018 study also showed that ECT was efficacious and cost-effective for patients with treatment-resistant depression.
However, the ECT debate continues. As reported early last year, there seems to be little common ground between clinicians who believe in the utility of ECT for depression and those who vehemently do not.
For the current review, Read and colleagues performed a Medline search for meta-analyses of the efficacy of ECT for depression. Meta-analyses were only included if they comprised placebo-controlled trials that compared ECT with SECT.
Once the meta-analyses were identified, investigators assessed their component studies. This assessment was conducted by two independent reviewers who used a 24-point quality scale developed by the authors. This scale, the authors note, combines the “risk of bias” domains of the Cochrane Handbook Risk of Bias Tool with criteria related to quality of study design and reporting, as well as several criteria specific to ECT research.
The two reviewers were blinded to each other’s ratings. Interrater differences were resolved collectively.
The literature search yielded 83 potential articles; after exclusion criteria were applied, 14 remained. Three of these articles were literature reviews, one discussed different types of statistical analyses used in ECT research, one was a meta-analysis in Hungarian, one was a meta-analysis that compared ECT with SECT in a selected population of elderly people, and three focused on transcranial magnetic stimulation.
This left five meta-analyses for the review. These included from 1 to 7 of the 11 studies in question:
- Janicak et al, 1985
- Kho, van Vreewijk, Simpson, & Zwinderman, 2003
- Mutz et al, 2019
- Pagnin, de Queiroz, Pini, & Cassano, 2004
- UK ECT Review Group, 2003
The review revealed shortcomings with both the meta-analyses and the studies they included. The investigators found that the mean quality scores of the 11 studies (10.27 ± 2.45 and 11.91 ± 2.91) were not statistically different between the two raters (P = .17), whose scores were significantly correlated (P = .001).
Among the 264 total ratings, the investigators found 55 inconsistencies, which were all resolved by discussion. The mean final quality score for the 11 studies included in the review was 12.27 ± 3.20/24; eight scored 13 or less.
The results of these studies do little to support the benefits of ECT relative to SECT, the reviewers note. Indeed, only four concluded that ECT is significantly superior to SECT. Five found no significant difference, and the remaining two had mixed results.
What’s more, only two of what the investigators describe as “higher quality” studies reported follow-up data. Of these, one produced an effect size of 0.065 favoring ECT, the other showed a small benefit in favor of SECT (effect size, 0.299).
The investigators describe the five meta-analyses included in the review as “flawed,” stating that the meta-analyses “pay little or no attention to the multiple limitations of the studies they include.”
These limitations include the number of patients included in the studies (which average 37 patients); lack of a description of randomization and blinding processes; lack of patient ratings; selective reporting of findings; and the absence of assessment of patient quality of life. Furthermore, the authors note that none of the 11 studies “convincingly” demonstrate double-blinding.
Given these shortcomings, the investigators say the meta-analyses of ECT fail to prove the following:
- The short- and long-term efficacy benefits of ECT over SECT;
- Whether ECT is effective among patients who have failed other treatments for depression;
- Whether ECT prevents ;
- Whether ECT improves patients’ quality of life;
- Whether ECT is more effective in women than men;
- Whether ECT is effective in children or adolescents.
“Shoddy” research
The authors conclude that the review’s findings demonstrate the weakness of evidence that currently supports the use of ECT for depression.
“I would never have guessed how shoddy some of this research was,” said review coauthor Irving Kirsch, PhD, a lecturer on medicine at Beth Israel Deaconess Medical Center, Boston. Many of these shortcomings, Kirsch said, involve blinding and placebo effects.
“It’s not clear how you could ever run a truly blinded trial of ECT, given how pronounced the immediate side effects are,” he told Medscape Medical News. “And one of the things that’s underappreciated is the pronounced responses to placebo treatment with depression and severe depression. These can last for a very long time.”
Kirsch noted that more invasive placebo treatments, such as SECT, tend to have more pronounced effects.
“Not all placebos are created equal. We know, for example, that placebo injections are more effective than placebo pills and that placebo surgery can be extremely powerful,” he said.
The authors call for an immediate suspension of ECT until new studies address these research shortcomings.
“The doctors who perform ECT aren’t evil or stupid, they’re just ignorant of the research. What they see is very temporary benefit in some of the patients. The research suggests that about a third – half at most – get a very temporary lift in mood, which seems to be the sort of euphoria you get from mild brain injury,” Read explained.
“I have seen people who haven’t spoken or eaten for several weeks start speaking and eating, but we know that 4 weeks later, they’re going to be just as depressed as they were, or worse. And now they’re going to have brain damage as well,” said Read.
He added that physicians often don’t see long-term patient outcomes, just the immediate effect of ECT.
A “lifesaver”
No recent randomized controlled trials regarding ECT have been conducted because “no IRB [institutional review board] on planet earth will allow such a trial because of the overwhelming evidence of efficacy and the risk of anesthesia with no ECT,” noted Mark S. George, MD, the Layton McCurdy Endowed Chair in Psychiatry at the Medical University of South Carolina, Charleston.
It is a “logical fallacy” to conclude that ECT does not work because the trials were flawed, said George, who was not involved with the current review
“This is not supported by anything they have looked at,” he told Medscape Medical News. “It’s not really a scientific study when you make conclusions that aren’t based on your data, or not what you set out to do. That’s what I find egregious here.”
The way he sees it, the utility of ECT is unquestionable. “It is our most effective acute treatment for depression, and it’s our most effective treatment for suicide,” he said.
“The authors of this review don’t see the patients that I see every day, who are catatonic, who can’t eat, who are suicidal. For those people, ECT is a lifesaver,” George added.
FDA’s position
Sameer Jauhar, MBChB, PhD, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust, London, was equally unimpressed with the quality of the review.
“I try to approach everything with an open mind,” he said. “But as a doctor, if I’m reading about evidence, I expect a well-conducted meta-analysis and/or very clear systematic review with an adequate level of peer review.”
The current review, said Jauhar, doesn’t meet these criteria. He said the article reads more like a narrative review, one in which the authors dictated their own arbitrary criteria of study quality.
Most important, he said, is the fact that ECT has been the focus of a great deal of research. “The best quality synthesis of the evidence I’ve come across is the UK ECT Review Group’s 2003 meta-analysis, published in The Lancet, which asked this very question. None of the studies has changed since then.”
Jauhar also noted that in 2018, the Food and Drug Administration reclassified ECT from class III (higher risk) to class II (moderate risk). Use of ECT was also limited to treatment of “catatonia or a severe major depressive episode associated with major depressive disorder or bipolar disorder in patients age 13 years and older who are treatment-resistant or who require a rapid response treatment due to the severity of their psychiatric or medical condition.”
The FDA also noted that “[t]he safe use of ECT for treatment of these conditions has been well studied and is better understood than other uses. Therefore, sufficient information exists to establish special controls that mitigate known risks and provide a reasonable assurance of safety and effectiveness for these two uses of ECT devices.”
As part of the FDA’s 2018 reclassification, ECT manufacturers were required to file a premarket approval application for all uses that were not reclassified. The full text of the order is available in the Federal Register.
“So the FDA has been through it, The Lancet has been through it, and the findings were clear,” said Jauhar. “It’s very easy to poke holes in studies that were conducted 30 or more years ago. But the fact is, the field has moved on.”
Jauhar acknowledged there are patients who have had bad experiences with ECT, and he accepts that such events occasionally occur. Nevertheless, he said,
Jauhar also noted that the journal in which the review was published has a 2019 CiteScore of 0.3 and ranks in the 15th percentile of the Scopus Clinical Psychology category. He further noted that Kirsch is a member of the journal’s editorial board.
“I would say that the level of peer review here was negligible at best,” Jauhar said. “In addition, the ‘findings’ are driven more by ideology than evidence.”
Asked to respond to Jauhar’s comments, Kirsch noted that although he is on the journal’s advisory board, he has not been actively involved. Kirsch added that he serves on about a dozen academic advisory boards and serves as a reviewer for many top scientific and medical journals, including The Journal of the American Medical Association and the New England Journal of Medicine.
“Our article was peer reviewed,” Kirsch said, “and we revised it following the first round of reviews.” The review process did not differ from those he has gone through with more than 250 published peer-reviewed articles on which he was an author or coauthor, he noted.
A growing movement
Despite such expert opposition, the movement to suspend ECT continues. Recently, Sarah Price Hancock, MS, CRC, CPMC, who is herself a recipient of more than 100 ECT treatments, authored an international petition to standardize, regulate, and audit the modality. Hancock hopes to present the document, which currently has more than 6600 signatures, to the American Psychiatric Association and similar international societies.
A version of the petition was presented to the UK’s National Health Service on July 2, the 59th anniversary of the death by suicide of Ernest Hemingway, who had received some 20 ECT treatments himself.
“Hopefully by his 60th anniversary, America and the world will be taking his death and the thousands living with adverse reactions more seriously by auditing, regulating, and tracking patients with a history of ECT to provide much needed comprehensive brain injury rehabilitation as necessary,” Hancock told Medscape Medical News.
Among the signatories of the petition is Sue Cunliffe, MbChB, who underwent ECT for depression in 2004, with devastating effects. “I was left really badly brain damaged, and so I’ve never been allowed to work again,” she told Medscape Medical News.
Cunliffe said the immediate effects of the treatment were profound. She said her hands shook, her balance and coordination were impaired, and her memories evaporated. However, she found a neuropsychologist who she says was able to help her recover control of her life. “Now at least I’m able to plan my life so that I can live with the brain damage.”
Kirsch acknowledged that sorting through the ECT literature can be daunting. “If you’re a physician, you try to keep up with the literature, but the problem is, the literature is so old and done in ways which would not pass muster right now. The data are really poor, and I guess it’s just that people aren’t aware of it.”
George agreed that the therapy is not without its shortcomings.
“Does ECT have cognitive side effects? Unfortunately, it does. But so do lots of lifesaving therapies in medicine, like cancer chemotherapy,” he said.
“Nobody really gets well with a single ECT session. It’s usually eight to 12 over 3 or 4 weeks. So it’s not particularly durable. That’s why we often combine ECT with other forms of brain stimulation,” George added.
He noted that the recent advent of alternative forms of ECT – including right unilateral ultrabrief pulse ECT and focal electrically administered seizure therapy – are beginning to address some of these shortcomings.
“The holy grail of brain stimulation is to be able to do things less invasively, and we’re moving slowly in that direction,” he said. “But right now, we don’t have anything that is as acutely as effective as ECT. It is our lifesaver at the moment.”
The review authors as well as George, Jauhar, Cunliffe, and Hancock report no relevant financial relationships.
This article first appeared on Medscape.com.