Children primed with DTaP vaccines have a weaker response to the pertussis component of the Tdap booster vaccine, compared with children primed with the whole-cell vaccine (DTwP), according to a study in Vaccine.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

Michael D. Decker, MD, and colleagues conducted a study in children aged 11-12 years who had been primed with DTaP (NCT01629589) that essentially mirrored one from 6 years earlier in children primed with DTwP when it was still the more commonly used vaccine (NCT00319553). This later study randomized 211 patients to Tdap5 and 212 to Tdap3, both licensed Tdap vaccines that had been used and compared in the earlier study. The geometric mean concentrations of antipertussis antibodies in DTaP-primed children after receiving either Tdap vaccine were lower than in DTwP-primed children receiving the same respective vaccines: only 35% as high for Tdap5 (31.0 vs. 86.7 endotoxin units/mL, respectively; 95% confidence interval, 30%-40%) and 32% as high (44.1 vs. 136 endotoxin units/mL; 95% CI, 28%-38%) for Tdap3.

The authors noted that, because studies including children primed with DTwP are usually much older, comparisons like the one made in this study can be unreliable because of various possible confounding factors – such as changes in manufacturing process, different assays used, changing characteristics in study populations or pertussis transmission, and so on – cannot be entirely excluded. However, one of the strengths of this study, they suggested, is that “all were randomized experimental studies conducted by Sanofi Pasteur using similar procedures (including time of sera collection), and sera from all were assayed by a single laboratory (GCI) employing consistent, [Food and Drug Administration]–accepted assays.”

They did note that estimates of mean pertussis antibodies was limited by sample sizes; however, they believed the results were sufficient for the comparisons in the study.

All authors of the study were employees of Sanofi Pasteur, which funded the study and also manufactures the Tdap5 vaccine.

[email protected]

SOURCE: Decker MD et al. Vaccine. 2019 Jul 10. doi: 10.1016/j.vaccine.2019.07.015.

Children primed with DTaP vaccines have a weaker response to the pertussis component of the Tdap booster vaccine, compared with children primed with the whole-cell vaccine (DTwP), according to a study in Vaccine.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

Michael D. Decker, MD, and colleagues conducted a study in children aged 11-12 years who had been primed with DTaP (NCT01629589) that essentially mirrored one from 6 years earlier in children primed with DTwP when it was still the more commonly used vaccine (NCT00319553). This later study randomized 211 patients to Tdap5 and 212 to Tdap3, both licensed Tdap vaccines that had been used and compared in the earlier study. The geometric mean concentrations of antipertussis antibodies in DTaP-primed children after receiving either Tdap vaccine were lower than in DTwP-primed children receiving the same respective vaccines: only 35% as high for Tdap5 (31.0 vs. 86.7 endotoxin units/mL, respectively; 95% confidence interval, 30%-40%) and 32% as high (44.1 vs. 136 endotoxin units/mL; 95% CI, 28%-38%) for Tdap3.

The authors noted that, because studies including children primed with DTwP are usually much older, comparisons like the one made in this study can be unreliable because of various possible confounding factors – such as changes in manufacturing process, different assays used, changing characteristics in study populations or pertussis transmission, and so on – cannot be entirely excluded. However, one of the strengths of this study, they suggested, is that “all were randomized experimental studies conducted by Sanofi Pasteur using similar procedures (including time of sera collection), and sera from all were assayed by a single laboratory (GCI) employing consistent, [Food and Drug Administration]–accepted assays.”

They did note that estimates of mean pertussis antibodies was limited by sample sizes; however, they believed the results were sufficient for the comparisons in the study.

All authors of the study were employees of Sanofi Pasteur, which funded the study and also manufactures the Tdap5 vaccine.

[email protected]

SOURCE: Decker MD et al. Vaccine. 2019 Jul 10. doi: 10.1016/j.vaccine.2019.07.015.

Children primed with DTaP vaccines have a weaker response to the pertussis component of the Tdap booster vaccine, compared with children primed with the whole-cell vaccine (DTwP), according to a study in Vaccine.

copyright Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

Michael D. Decker, MD, and colleagues conducted a study in children aged 11-12 years who had been primed with DTaP (NCT01629589) that essentially mirrored one from 6 years earlier in children primed with DTwP when it was still the more commonly used vaccine (NCT00319553). This later study randomized 211 patients to Tdap5 and 212 to Tdap3, both licensed Tdap vaccines that had been used and compared in the earlier study. The geometric mean concentrations of antipertussis antibodies in DTaP-primed children after receiving either Tdap vaccine were lower than in DTwP-primed children receiving the same respective vaccines: only 35% as high for Tdap5 (31.0 vs. 86.7 endotoxin units/mL, respectively; 95% confidence interval, 30%-40%) and 32% as high (44.1 vs. 136 endotoxin units/mL; 95% CI, 28%-38%) for Tdap3.

The authors noted that, because studies including children primed with DTwP are usually much older, comparisons like the one made in this study can be unreliable because of various possible confounding factors – such as changes in manufacturing process, different assays used, changing characteristics in study populations or pertussis transmission, and so on – cannot be entirely excluded. However, one of the strengths of this study, they suggested, is that “all were randomized experimental studies conducted by Sanofi Pasteur using similar procedures (including time of sera collection), and sera from all were assayed by a single laboratory (GCI) employing consistent, [Food and Drug Administration]–accepted assays.”

They did note that estimates of mean pertussis antibodies was limited by sample sizes; however, they believed the results were sufficient for the comparisons in the study.

All authors of the study were employees of Sanofi Pasteur, which funded the study and also manufactures the Tdap5 vaccine.

[email protected]

SOURCE: Decker MD et al. Vaccine. 2019 Jul 10. doi: 10.1016/j.vaccine.2019.07.015.

NASHVILLE, TENN. – Surgery and medication each offer a generally safe and effective approach for managing second-trimester fetal demise, according to Sarah W. Prager, MD.

Therefore, in the absence of clear contraindications in settings where both options are available, patient preference should prevail, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington, Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

However, shared decision-making is imperative, she said.

Shared decision-making “can be extremely important for satisfaction with this process,” she said, explaining that provider-driven decisions can be paternalistic and often are based on what the provider might do in the same situation.

“But that may not be what the patient wants,” she added.

Conversely, patient-led decision-making can lead to information overload.

“She’s coming to you because you’re the expert. She wants your opinion on this,” Dr. Prager said, noting that sharing the process through “information transfer” allows for the “best, most appropriate decision” to be made.

“Patient engagement is the practice of actively involving and supporting the patient in health care and treatment decision-making activities, and this is really what I’m talking about,” she said, adding that patient engagement is “critically important in many situations, and especially in the setting of pregnancy loss.”

That’s because patients feel powerless in this situation, she explained. Engaging them in the decision-making process can “give them a little bit of that power back” by respecting autonomy, enhancing agency, improving health status, reducing decisional conflict, and limiting test use, thereby improving overall satisfaction.

Two randomized control trials, each designed to compare surgical management and medical management for terminations at up to 20 weeks of gestation, highlight the role and importance of patient preference, Dr. Prager said.

The first – a 2004 study – was stopped early because of slow enrollment, with 29 of 47 eligible subjects declining randomization. Among 93% of those who declined, there was a preference for surgical management. The second, a 2010 study, enrolled 122 patients after 107 of 229 eligible subjects (47%) declined randomization, again because most (67%) preferred surgery (BJOG. 2004;111[2]:148-53; BJOG. 2010;117[12]:1512-20).

Reasons given for preferring surgical management included less psychological trauma and deeper anesthesia, whereas reasons given for induction preference included less wait time and a desire to avoid general anesthesia.

Helping patients make the best decision requires a discussion about potential complications for each approach, Dr. Prager said.

Surgical management, which involves dilation and evacuation (D&E), is used for about 95% of second-trimester abortions overall, but medical management may be underreported, particularly for management of pregnancy loss, Dr. Prager said. “We don’t have clear statistics” in that setting.

The overall rate of complications is low for surgical management, with data suggesting a rate of up to 4%. Uterine perforation occurs in 0.2%-0.3% of procedures, cervical laceration occurs in up to 1%, and retained placenta occurs in less than 1%, she said.

The complication rate for medical management – induction with either misoprostol or mifepristone + misoprostol (the latter is the recommended approach) – is much higher at up to 29%, but that includes retained placenta, which happens in up to 10% of procedures. Uterine rupture occurs in 0.04%-0.28% of procedures, she said.

“With either surgical management or medication management of pregnancy loss, we need to keep in mind the possibility of disseminated intravascular coagulation, which is rare, but certainly possible,” she said.

Other factors that may be important to patients deciding between surgical and medical management for second-trimester fetal loss include:

• Anesthesia, which is local plus intravenous sedation for surgery, compared with IV narcotics and potentially an epidural or other type of regional anesthesia for medical management.
• Duration, which is 5-20 minutes for surgery, compared with 6-11 hours with mifepristone + misoprostol, and up to 20 hours with misoprostol alone.
• Location, which is done on an outpatient basis for surgery, compared with inpatient care for medical management.
• Cost, which is $1,000-$5,000 for surgery vs. $3,000-$9,000 for medical management.
• Contact with the fetus, which typically involves the possibility of partial viewing and an opportunity to obtain footprints as a memento if an intact procedure is attempted during surgery vs. full viewing and possibly holding the baby after delivery following medical management. This is often the key deciding factor for patients.
• Provider factors, in terms of training and skills. Surgery involves a need for specialized training, whereas medical management requires no extra training, she said, adding that “not all ob.gyns. across the country are competent or comfortable providing a D&E, particularly in the later second-trimester time period.” However, the availability of family planing fellowships will increase the number of centers across the country where both options will be available, she noted.
• The possibility of fetal autopsy, which surgery often (but not always) allows, but medical management always allows.
• Involvement level, which is provider heavy for surgery vs. patient heavy for medical management.

“Moving toward an evidence-based, patient-centered care model requires a lot of us, as providers, to really work at dropping our assumptions. We often have strong opinions about what we think we would do in that setting, and it can be tricky for us to set that aside and allow patients to really ask questions and discuss their values so that we can then advocate best for our patients after they know exactly what their options are,” she said.

Dr. Prager reported having no relevant disclosures.

[email protected]

NASHVILLE, TENN. – Surgery and medication each offer a generally safe and effective approach for managing second-trimester fetal demise, according to Sarah W. Prager, MD.

Therefore, in the absence of clear contraindications in settings where both options are available, patient preference should prevail, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington, Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

However, shared decision-making is imperative, she said.

Shared decision-making “can be extremely important for satisfaction with this process,” she said, explaining that provider-driven decisions can be paternalistic and often are based on what the provider might do in the same situation.

“But that may not be what the patient wants,” she added.

Conversely, patient-led decision-making can lead to information overload.

“She’s coming to you because you’re the expert. She wants your opinion on this,” Dr. Prager said, noting that sharing the process through “information transfer” allows for the “best, most appropriate decision” to be made.

“Patient engagement is the practice of actively involving and supporting the patient in health care and treatment decision-making activities, and this is really what I’m talking about,” she said, adding that patient engagement is “critically important in many situations, and especially in the setting of pregnancy loss.”

That’s because patients feel powerless in this situation, she explained. Engaging them in the decision-making process can “give them a little bit of that power back” by respecting autonomy, enhancing agency, improving health status, reducing decisional conflict, and limiting test use, thereby improving overall satisfaction.

Two randomized control trials, each designed to compare surgical management and medical management for terminations at up to 20 weeks of gestation, highlight the role and importance of patient preference, Dr. Prager said.

The first – a 2004 study – was stopped early because of slow enrollment, with 29 of 47 eligible subjects declining randomization. Among 93% of those who declined, there was a preference for surgical management. The second, a 2010 study, enrolled 122 patients after 107 of 229 eligible subjects (47%) declined randomization, again because most (67%) preferred surgery (BJOG. 2004;111[2]:148-53; BJOG. 2010;117[12]:1512-20).

Reasons given for preferring surgical management included less psychological trauma and deeper anesthesia, whereas reasons given for induction preference included less wait time and a desire to avoid general anesthesia.

Helping patients make the best decision requires a discussion about potential complications for each approach, Dr. Prager said.

Surgical management, which involves dilation and evacuation (D&E), is used for about 95% of second-trimester abortions overall, but medical management may be underreported, particularly for management of pregnancy loss, Dr. Prager said. “We don’t have clear statistics” in that setting.

The overall rate of complications is low for surgical management, with data suggesting a rate of up to 4%. Uterine perforation occurs in 0.2%-0.3% of procedures, cervical laceration occurs in up to 1%, and retained placenta occurs in less than 1%, she said.

The complication rate for medical management – induction with either misoprostol or mifepristone + misoprostol (the latter is the recommended approach) – is much higher at up to 29%, but that includes retained placenta, which happens in up to 10% of procedures. Uterine rupture occurs in 0.04%-0.28% of procedures, she said.

“With either surgical management or medication management of pregnancy loss, we need to keep in mind the possibility of disseminated intravascular coagulation, which is rare, but certainly possible,” she said.

Other factors that may be important to patients deciding between surgical and medical management for second-trimester fetal loss include:

• Anesthesia, which is local plus intravenous sedation for surgery, compared with IV narcotics and potentially an epidural or other type of regional anesthesia for medical management.
• Duration, which is 5-20 minutes for surgery, compared with 6-11 hours with mifepristone + misoprostol, and up to 20 hours with misoprostol alone.
• Location, which is done on an outpatient basis for surgery, compared with inpatient care for medical management.
• Cost, which is $1,000-$5,000 for surgery vs. $3,000-$9,000 for medical management.
• Contact with the fetus, which typically involves the possibility of partial viewing and an opportunity to obtain footprints as a memento if an intact procedure is attempted during surgery vs. full viewing and possibly holding the baby after delivery following medical management. This is often the key deciding factor for patients.
• Provider factors, in terms of training and skills. Surgery involves a need for specialized training, whereas medical management requires no extra training, she said, adding that “not all ob.gyns. across the country are competent or comfortable providing a D&E, particularly in the later second-trimester time period.” However, the availability of family planing fellowships will increase the number of centers across the country where both options will be available, she noted.
• The possibility of fetal autopsy, which surgery often (but not always) allows, but medical management always allows.
• Involvement level, which is provider heavy for surgery vs. patient heavy for medical management.

“Moving toward an evidence-based, patient-centered care model requires a lot of us, as providers, to really work at dropping our assumptions. We often have strong opinions about what we think we would do in that setting, and it can be tricky for us to set that aside and allow patients to really ask questions and discuss their values so that we can then advocate best for our patients after they know exactly what their options are,” she said.

Dr. Prager reported having no relevant disclosures.

[email protected]

NASHVILLE, TENN. – Surgery and medication each offer a generally safe and effective approach for managing second-trimester fetal demise, according to Sarah W. Prager, MD.

Therefore, in the absence of clear contraindications in settings where both options are available, patient preference should prevail, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington, Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

However, shared decision-making is imperative, she said.

Shared decision-making “can be extremely important for satisfaction with this process,” she said, explaining that provider-driven decisions can be paternalistic and often are based on what the provider might do in the same situation.

“But that may not be what the patient wants,” she added.

Conversely, patient-led decision-making can lead to information overload.

“She’s coming to you because you’re the expert. She wants your opinion on this,” Dr. Prager said, noting that sharing the process through “information transfer” allows for the “best, most appropriate decision” to be made.

“Patient engagement is the practice of actively involving and supporting the patient in health care and treatment decision-making activities, and this is really what I’m talking about,” she said, adding that patient engagement is “critically important in many situations, and especially in the setting of pregnancy loss.”

That’s because patients feel powerless in this situation, she explained. Engaging them in the decision-making process can “give them a little bit of that power back” by respecting autonomy, enhancing agency, improving health status, reducing decisional conflict, and limiting test use, thereby improving overall satisfaction.

Two randomized control trials, each designed to compare surgical management and medical management for terminations at up to 20 weeks of gestation, highlight the role and importance of patient preference, Dr. Prager said.

The first – a 2004 study – was stopped early because of slow enrollment, with 29 of 47 eligible subjects declining randomization. Among 93% of those who declined, there was a preference for surgical management. The second, a 2010 study, enrolled 122 patients after 107 of 229 eligible subjects (47%) declined randomization, again because most (67%) preferred surgery (BJOG. 2004;111[2]:148-53; BJOG. 2010;117[12]:1512-20).

Reasons given for preferring surgical management included less psychological trauma and deeper anesthesia, whereas reasons given for induction preference included less wait time and a desire to avoid general anesthesia.

Helping patients make the best decision requires a discussion about potential complications for each approach, Dr. Prager said.

Surgical management, which involves dilation and evacuation (D&E), is used for about 95% of second-trimester abortions overall, but medical management may be underreported, particularly for management of pregnancy loss, Dr. Prager said. “We don’t have clear statistics” in that setting.

The overall rate of complications is low for surgical management, with data suggesting a rate of up to 4%. Uterine perforation occurs in 0.2%-0.3% of procedures, cervical laceration occurs in up to 1%, and retained placenta occurs in less than 1%, she said.

The complication rate for medical management – induction with either misoprostol or mifepristone + misoprostol (the latter is the recommended approach) – is much higher at up to 29%, but that includes retained placenta, which happens in up to 10% of procedures. Uterine rupture occurs in 0.04%-0.28% of procedures, she said.

“With either surgical management or medication management of pregnancy loss, we need to keep in mind the possibility of disseminated intravascular coagulation, which is rare, but certainly possible,” she said.

Other factors that may be important to patients deciding between surgical and medical management for second-trimester fetal loss include:

• Anesthesia, which is local plus intravenous sedation for surgery, compared with IV narcotics and potentially an epidural or other type of regional anesthesia for medical management.
• Duration, which is 5-20 minutes for surgery, compared with 6-11 hours with mifepristone + misoprostol, and up to 20 hours with misoprostol alone.
• Location, which is done on an outpatient basis for surgery, compared with inpatient care for medical management.
• Cost, which is $1,000-$5,000 for surgery vs. $3,000-$9,000 for medical management.
• Contact with the fetus, which typically involves the possibility of partial viewing and an opportunity to obtain footprints as a memento if an intact procedure is attempted during surgery vs. full viewing and possibly holding the baby after delivery following medical management. This is often the key deciding factor for patients.
• Provider factors, in terms of training and skills. Surgery involves a need for specialized training, whereas medical management requires no extra training, she said, adding that “not all ob.gyns. across the country are competent or comfortable providing a D&E, particularly in the later second-trimester time period.” However, the availability of family planing fellowships will increase the number of centers across the country where both options will be available, she noted.
• The possibility of fetal autopsy, which surgery often (but not always) allows, but medical management always allows.
• Involvement level, which is provider heavy for surgery vs. patient heavy for medical management.

“Moving toward an evidence-based, patient-centered care model requires a lot of us, as providers, to really work at dropping our assumptions. We often have strong opinions about what we think we would do in that setting, and it can be tricky for us to set that aside and allow patients to really ask questions and discuss their values so that we can then advocate best for our patients after they know exactly what their options are,” she said.

Dr. Prager reported having no relevant disclosures.

[email protected]

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

Psoriasis is a common immune-mediated inflammatory skin disorder that affects up to 3.2% of adults in the United States.¹  It is a T_H1, T_H17, and T_H22 inflammatory disease resulting in increased levels of cytokines in the skin, including IFN-γ, tumor necrosis factor (TNF), IL-17, and IL-22. Dendritic antigen-presenting cells also are increased in the skin of patients with psoriasis resulting in increased levels of IL-23.²  Although skin disease often is its most prominent and sometimes its only documented manifestation, an understanding of psoriasis as a chronic multisystem inflammatory disorder is essential to optimize outcomes.^1,3  Multiple comorbidities that may affect treatment selection often are associated with psoriasis, including psoriatic arthritis, cardiovascular disease, depression, obesity, metabolic syndrome, cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease. 

As with other immune-mediated inflammatory diseases, it has been hypothesized that psoriasis may influence comorbidities through shared genetic risks, environmental factors, and pathogenic factors or inflammatory pathways.^2-4 For example, emerging evidence suggests that comorbidities such as metabolic syndrome may be related to the chronic inflammation that accompanies psoriasis, a finding that has important clinical implications.³ 

The interplay and dependence or interdependence of psoriasis and its comorbidities is complex, and it is an area deserving of vigorous research.¹ At present, observational and epidemiological data such as the present case suggest that effective treatment of psoriasis could lead to benefits “beyond the skin” and potentially even prevent future disease-associated comorbidity.^1-3

Metabolic Comorbidities and Psoriasis Treatment

Although the prevalence of CVD and CVD risk factors is increased in patients with psoriasis, studies suggest that the suppression of systemic inflammation that accompanies adequate psoriasis treatment, particularly in patients with moderate to severe disease, may decrease the risk for cardiovascular comorbidities.⁵ For example, a number of studies have found treatment of psoriasis with methotrexate may decrease the risk for cardiovascular events, including ischemic heart disease, stroke, and cardiovascular death.^6-10 Low-dose methotrexate has been shown to be particularly advantageous for decreasing CVD in patients with psoriasis.^5,8 

Tumor necrosis factor α inhibitors, which are frequently used for moderate to severe plaque psoriasis, also may notably decrease cardiovascular risk.⁵ One study showed a significant decrease in the risk for myocardial infarction in patients with psoriasis who were treated with TNF-α inhibitors (hazard ratio, 0.50; 95% CI, 0.32-0.79)¹¹; other studies have confirmed this benefit.^12-17 Moreover, the reduction in cardiovascular events may be greater with TNF-α inhibitors than with methotrexate when the former is used for psoriasis treatment, with longer duration of TNF-α inhibition leading to greater risk reduction.^18,19 

In patients with severe psoriasis, treatment with TNF-α inhibitors has been associated with improvements in subclinical CVD (abnormalities in echocardiogram), improved coronary microvascular function (determined by transthoracic Doppler echocardiography), and reduced progression in coronary artery disease (assessed by coronary computed tomography).^20-22 Improvement in endothelial function (brachial artery reactivity) and carotid arterial stiffness also has been reported following 6 months of treatment with adalimumab for moderate to severe psoriasis.²¹ 

Data concerning potential cardiovascular risk reduction with treatment of psoriasis utilizing newer agents are continuing to emerge. To date, no increase in the incidence of major adverse cardiovascular events has been shown in patients with psoriasis treated with anti–IL-17 agents, such as secukinumab; however, additional long-term studies are needed.^18,23-25 

Apremilast, an oral phosphodiesterase 4 inhibitor, is another addition to the psoriasis armamentarium.²⁶ No increase in the risk for major cardiac events has been shown in randomized controlled trials of patients with psoriasis receiving apremilast for up to 156 weeks.^27,28 As with secukinumab, additional long-term, large-scale studies are needed to determine the effects of apremilast on cardiovascular risk in patients with psoriasis.⁵ 

Other Comorbidities

Effective treatment of psoriasis also appears to benefit various other comorbidities. Numerous studies have shown an increased incidence of depression in patients with psoriasis vs controls and a concurrent improvement in psychiatric symptoms with psoriasis disease control.¹ For instance, a multicenter, randomized, open-label study of 352 patients with psoriasis showed treatment with etanercept, a TNF inhibitor, significantly improved scores for concomitant depression and anxiety (P<.05).²⁹ Similarly, a double-blind, randomized clinical trial of patients with psoriasis found significant improvement in depression at 12 weeks in patients treated with adalimumab vs placebo (P<.001).³⁰ Likewise, a multicenter phase 3 trial of more than 600 psoriatic patients showed improved Beck depression inventory and Hamilton depression rating scale scores at 12 weeks in patients with psoriasis treated with etanercept compared to placebo.³¹ 

A much larger analysis of 7490 patients with psoriasis compared the rates of depression among patients receiving biologic therapy, phototherapy, and conventional systemic therapy. The greatest impact on depression symptoms was seen with biologic therapy (incidence rate, 3.01/100 patient-years), followed by conventional systemic therapy (5.70/100 patient-years), and phototherapy (5.85/100 patient-years).³²

Uveitis, or inflammation of the middle layer of the eye (the uvea), frequently is seen in patients with psoriasis. In a cohort study of 60,000 patients with mild psoriasis and more than 7000 patients with severe psoriasis, the incidence of uveitis in patients was significantly increased in both patients with severe disease and those with mild disease (P<.001 for both).³³ In a case series of 8 patients with concomitant psoriasis and uveitis, 4 patients were treated with infliximab and 4 with adalimumab; 7 patients treated achieved remission of their uveitis.³⁴ 

Role of the TNF-α Blockade in Sickle Cell Disease

Presently, no reported human studies have shown TNF-α blockade as a possible treatment of sickle cell disease.³⁵ However, increased levels of TNF-α have been shown to contribute to the onset of sickle cell crises and to the severity of sickle cell disease due to their integral role in the development of vascular wall dysfunction and ischemia.^35,36 Studies have shown that TNF-α is released in homozygous sickle cell anemia (HbSS) disease and impedes blood flow during sickle cell crisis, resulting in worsening ischemia and painful infarction.^35,36 Moreover, cytokine analysis has shown significantly (P<.05) elevated levels of TNF-α during sickle cell crises and at baseline in patients with HbSS vs healthy controls, suggesting a possible role of TNF-α in the pathogenesis of sickle cell crisis.³⁶ 

The case patient reported a 50% reduction in pain level and the use of pain medications that overlapped with the initiation of adalimumab for treatment of her psoriasis. Moreover, although radiographs showed possible psoriatic changes of the distal metatarsal row, she described sickle cell pain and pain crises that were uncharacteristic of psoriatic arthralgia.³⁵ Although these findings are observational in nature and limited to one patient, they do suggest an interesting hypothesis. If a common inflammatory mediator is the culprit, it is possible that TNF-α inhibitors could be the preferred treatment option for patients with psoriasis and comorbid HbSS or HbSC disease. Further studies are needed to analyze the role of TNF-α inhibition in sickle cell disease.

Bottom Line

Psoriasis may influence comorbidities through shared genetic risks, environmental factors, or inflammatory pathways. Improvement in metabolic and other comorbidities have been shown with the effective treatment of psoriasis. The case described here showed improvement in sickle cell crises and pain with treatment of psoriasis with adalimumab. Tumor necrosis factor inhibitors may be an optimal choice for patients with both psoriasis and sickle cell disease. 

SAN DIEGO – Two leading figures in microbiome research took time during the annual Digestive Disease Week to share their perspective with members of the press. Identifying key research presented at the meeting and painting a broader picture of trends and challenges in research on the interplay with the microbiota with gut health, Colleen Kelly, MD, of Brown University, Providence, R.I., cochair and principal investigator, AGA FMT Registry Steering Committee, led off the round table with a discussion of human research on fecal microbial transplantation (FMT) and obesity.

Purna Kashyap, MBBS, of the Mayo Clinic, Rochester, Minn., member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board, delved into the potential for donor microbiota transplant to address small bowel disorders, such as small intestinal bacterial overgrowth, and provided commentary regarding the potential – and limitations – of using FMT in functional bowel disorders such as irritable bowel syndrome (IBS).

Obesity

Dr. Kelly noted that two abstracts at the conference presented data about FMT in obesity. The first study was presented by Jessica Allegretti, MD, a gastroenterologist at Brigham and Women’s Hospital, Boston; the second study was presented by Elaine Yu, MD, an endocrinologist at Massachusetts General Hospital, Boston.

The two studies shared some similarities, but had some differences, said Dr. Kelly. “They both used lean donor encapsulated FMT ... and they both were placebo controlled, using placebo capsules.” The first study looked at metabolically healthy obese patients, while the second study included patients with mild to moderate insulin resistance.

Dr. Allegretti’s work looked at the effect that FMT from lean donors had on levels of a satiety peptide, glucagonlike peptide–1 (GLP-1), while also looking at changes in weight and microbiota, as well as safety. Patients received an initial 30-capsule dose as well as two later doses of 12 capsules each. The 22-patient study, in which individuals were randomized 1:1 to FMT or placebo capsules, didn’t show statistically significant changes in GLP-1 levels or body mass index with FMT over the 12-week study period. “But they were able to show engraftment, which I think is an important thing that you do wonder about – over this period of time, the bacteria that came from the lean donor actually engrafted into the recipient and affected the diversity. The recipient became more similar to the donor,” said Dr. Kelly.

There were some clues among the findings that engraftment was effecting metabolic change in the recipient, she said, including differences in bile acid conversion among gut bacteria; also, lower levels of the primary bile acid taurocholic acid in recipients after FMT. “So it was a negative study in what she was looking for, but an example of these smaller studies kind of pushing the field along.”

In discussing the study presented by Dr. Yu that examined lean donor FMT in individuals with insulin resistance, Dr. Kelly said, “It was actually pretty sophisticated.” By using hyperinsulinemic euglycemic clamping, the investigators were able to measure insulin sensitivity based on glucose load. In this study of 24 individuals randomized 1:1 to receive FMT or placebo capsules, recipients received weekly doses over a period of 6 weeks. Here again, though Dr. Yu and colleagues again found engraftment, “they did not find the big changes in metabolic parameters that they hoped that they would,” said Dr. Kelly.

These two studies furthered previous work completed in the Netherlands examining lean donor FMT for individuals with metabolic syndrome. “Those [studies] did show both engraftment and some changes in insulin resistance,” but they were also small studies, noted Dr. Kelly. Dr. Kashyap pointed out that the earlier studies had shown in a subgroup analysis that response to FMT was limited to those patients who lacked microbial diversity pretransplant.

This makes some mechanistic sense when thinking about FMT’s greatest success to date: Treating Clostridioides difficile infection, a condition whose very hallmark is dysbiosis characterized by monospecies gut domination, noted Dr. Kashyap.

Added Dr. Kelly, “I think everyone’s hoping there’s going to be this pill that’s going to make us skinny, but I don’t think we’re going to find that with FMT and obesity. I do think these studies are important, because there’s so much animal data already, and we’re kind of like, ‘How much more can you do in mice?’ ” By translating this preclinical work into humans, the mechanisms of obesity and the role of the microbiome can be better understood.

IBS

Turning to functional bowel disorders, Dr. Kelly pointed out a new study examining FMT for IBS. “So far, the research has been pretty disappointing,” she noted. The study, presented by Prashant Singh, MBBS, a gastroenterology fellow at Beth Israel Deaconess Medical Center, Boston, examined FMT for patients with moderate to severe diarrhea-predominant IBS. The study had four arms, randomizing the 44 participants to FMT alone; pretreatment with metronidazole and ciprofloxacin or rifaximin, each followed by FMT; or placebo. “It really didn’t show any differences in their severity of IBS in any group; so no effect: a negative study,” said Dr. Kelly.

“It’s challenging. FMT is an appealing strategy because we don’t have to put a lot of thought process into it,” said Dr. Kashyap, but it’s no panacea. “We aren’t going to be able to treat everybody with FMT.

“The challenge with IBS is that if we look at all the compositional studies, the majority of them show that at least a big subset of patients with IBS already have a normal-appearing microbiome,” said Dr. Kashyap. In those patients, “It’s very hard to know what FMT is doing.” He noted that IBS subclassifications are made by pathophysiology, without regard to the intestinal microbiome, so these classifications may not be useful for determining who may benefit from FMT.

“Again, there’s always an opportunity to learn from these studies,” whether they’re positive or negative, as long as they’re well done, said Dr. Kashyap. “There’s always an opportunity to go back and see, was there a specific subgroup of patients who responded, where there might be one or more causes which might be more amenable” to FMT.

Small intestine

And most intestinal microbial research to date, noted Dr. Kelly, has focused on the colon. “Most of our knowledge is of fecal microbiota.” New techniques including double-balloon enteroscopy of the small bowel have promise to “provide completely new information about patterns of bacteria throughout the small bowel,” and of the role of small bowel bacteria in overall gut health, she said.

“The role of the small bowel has been ignored because of accessibility,” agreed Dr. Kashyap. There’s a current focus on research into enteroscopy and other techniques to sample small intestine microbiota, he said.

In a podium presentation, Eugene Chang, MD, Martin Boyer Professor in the University of Chicago’s department of medicine, gave a broad overview of how the small intestine microbiome modulates lipid regulation. This choice of topic for the Charles M. Mansbach Memorial Lecture shows that gastroenterologists are recognizing the importance of microbiome along the entire span of the gut, said Dr. Kashyap. Dr. Chang’s approach, he added, represents a departure in that “it’s not simply just looking at what’s present and what’s not, but seeing what’s functionally relevant to metabolism.”

“We always have known that the small intestine is the workhorse; that’s where everything happens” in terms of motility, absorption, and digestion, said Dr. Kashyap. “But because of our inability to reach it easily we’ve always chosen to ignore it; we always go after the low-hanging fruit.” Despite challenges, more microbiome research should be small-bowel focused. “Eventually, it’s no pain, no gain.”

Dr. Kashyap is on the advisory board of uBiome, and is an ad hoc advisory board member for Salix Pharmaceuticals. Dr. Kelly reported no conflicts of interest.

This story was updated on July 30, 2019.

[email protected]

SAN DIEGO – Two leading figures in microbiome research took time during the annual Digestive Disease Week to share their perspective with members of the press. Identifying key research presented at the meeting and painting a broader picture of trends and challenges in research on the interplay with the microbiota with gut health, Colleen Kelly, MD, of Brown University, Providence, R.I., cochair and principal investigator, AGA FMT Registry Steering Committee, led off the round table with a discussion of human research on fecal microbial transplantation (FMT) and obesity.

Purna Kashyap, MBBS, of the Mayo Clinic, Rochester, Minn., member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board, delved into the potential for donor microbiota transplant to address small bowel disorders, such as small intestinal bacterial overgrowth, and provided commentary regarding the potential – and limitations – of using FMT in functional bowel disorders such as irritable bowel syndrome (IBS).

Obesity

Dr. Kelly noted that two abstracts at the conference presented data about FMT in obesity. The first study was presented by Jessica Allegretti, MD, a gastroenterologist at Brigham and Women’s Hospital, Boston; the second study was presented by Elaine Yu, MD, an endocrinologist at Massachusetts General Hospital, Boston.

The two studies shared some similarities, but had some differences, said Dr. Kelly. “They both used lean donor encapsulated FMT ... and they both were placebo controlled, using placebo capsules.” The first study looked at metabolically healthy obese patients, while the second study included patients with mild to moderate insulin resistance.

Dr. Allegretti’s work looked at the effect that FMT from lean donors had on levels of a satiety peptide, glucagonlike peptide–1 (GLP-1), while also looking at changes in weight and microbiota, as well as safety. Patients received an initial 30-capsule dose as well as two later doses of 12 capsules each. The 22-patient study, in which individuals were randomized 1:1 to FMT or placebo capsules, didn’t show statistically significant changes in GLP-1 levels or body mass index with FMT over the 12-week study period. “But they were able to show engraftment, which I think is an important thing that you do wonder about – over this period of time, the bacteria that came from the lean donor actually engrafted into the recipient and affected the diversity. The recipient became more similar to the donor,” said Dr. Kelly.

There were some clues among the findings that engraftment was effecting metabolic change in the recipient, she said, including differences in bile acid conversion among gut bacteria; also, lower levels of the primary bile acid taurocholic acid in recipients after FMT. “So it was a negative study in what she was looking for, but an example of these smaller studies kind of pushing the field along.”

In discussing the study presented by Dr. Yu that examined lean donor FMT in individuals with insulin resistance, Dr. Kelly said, “It was actually pretty sophisticated.” By using hyperinsulinemic euglycemic clamping, the investigators were able to measure insulin sensitivity based on glucose load. In this study of 24 individuals randomized 1:1 to receive FMT or placebo capsules, recipients received weekly doses over a period of 6 weeks. Here again, though Dr. Yu and colleagues again found engraftment, “they did not find the big changes in metabolic parameters that they hoped that they would,” said Dr. Kelly.

These two studies furthered previous work completed in the Netherlands examining lean donor FMT for individuals with metabolic syndrome. “Those [studies] did show both engraftment and some changes in insulin resistance,” but they were also small studies, noted Dr. Kelly. Dr. Kashyap pointed out that the earlier studies had shown in a subgroup analysis that response to FMT was limited to those patients who lacked microbial diversity pretransplant.

This makes some mechanistic sense when thinking about FMT’s greatest success to date: Treating Clostridioides difficile infection, a condition whose very hallmark is dysbiosis characterized by monospecies gut domination, noted Dr. Kashyap.

Added Dr. Kelly, “I think everyone’s hoping there’s going to be this pill that’s going to make us skinny, but I don’t think we’re going to find that with FMT and obesity. I do think these studies are important, because there’s so much animal data already, and we’re kind of like, ‘How much more can you do in mice?’ ” By translating this preclinical work into humans, the mechanisms of obesity and the role of the microbiome can be better understood.

IBS

Turning to functional bowel disorders, Dr. Kelly pointed out a new study examining FMT for IBS. “So far, the research has been pretty disappointing,” she noted. The study, presented by Prashant Singh, MBBS, a gastroenterology fellow at Beth Israel Deaconess Medical Center, Boston, examined FMT for patients with moderate to severe diarrhea-predominant IBS. The study had four arms, randomizing the 44 participants to FMT alone; pretreatment with metronidazole and ciprofloxacin or rifaximin, each followed by FMT; or placebo. “It really didn’t show any differences in their severity of IBS in any group; so no effect: a negative study,” said Dr. Kelly.

“It’s challenging. FMT is an appealing strategy because we don’t have to put a lot of thought process into it,” said Dr. Kashyap, but it’s no panacea. “We aren’t going to be able to treat everybody with FMT.

“The challenge with IBS is that if we look at all the compositional studies, the majority of them show that at least a big subset of patients with IBS already have a normal-appearing microbiome,” said Dr. Kashyap. In those patients, “It’s very hard to know what FMT is doing.” He noted that IBS subclassifications are made by pathophysiology, without regard to the intestinal microbiome, so these classifications may not be useful for determining who may benefit from FMT.

“Again, there’s always an opportunity to learn from these studies,” whether they’re positive or negative, as long as they’re well done, said Dr. Kashyap. “There’s always an opportunity to go back and see, was there a specific subgroup of patients who responded, where there might be one or more causes which might be more amenable” to FMT.

Small intestine

And most intestinal microbial research to date, noted Dr. Kelly, has focused on the colon. “Most of our knowledge is of fecal microbiota.” New techniques including double-balloon enteroscopy of the small bowel have promise to “provide completely new information about patterns of bacteria throughout the small bowel,” and of the role of small bowel bacteria in overall gut health, she said.

“The role of the small bowel has been ignored because of accessibility,” agreed Dr. Kashyap. There’s a current focus on research into enteroscopy and other techniques to sample small intestine microbiota, he said.

In a podium presentation, Eugene Chang, MD, Martin Boyer Professor in the University of Chicago’s department of medicine, gave a broad overview of how the small intestine microbiome modulates lipid regulation. This choice of topic for the Charles M. Mansbach Memorial Lecture shows that gastroenterologists are recognizing the importance of microbiome along the entire span of the gut, said Dr. Kashyap. Dr. Chang’s approach, he added, represents a departure in that “it’s not simply just looking at what’s present and what’s not, but seeing what’s functionally relevant to metabolism.”

“We always have known that the small intestine is the workhorse; that’s where everything happens” in terms of motility, absorption, and digestion, said Dr. Kashyap. “But because of our inability to reach it easily we’ve always chosen to ignore it; we always go after the low-hanging fruit.” Despite challenges, more microbiome research should be small-bowel focused. “Eventually, it’s no pain, no gain.”

Dr. Kashyap is on the advisory board of uBiome, and is an ad hoc advisory board member for Salix Pharmaceuticals. Dr. Kelly reported no conflicts of interest.

This story was updated on July 30, 2019.

[email protected]

SAN DIEGO – Two leading figures in microbiome research took time during the annual Digestive Disease Week to share their perspective with members of the press. Identifying key research presented at the meeting and painting a broader picture of trends and challenges in research on the interplay with the microbiota with gut health, Colleen Kelly, MD, of Brown University, Providence, R.I., cochair and principal investigator, AGA FMT Registry Steering Committee, led off the round table with a discussion of human research on fecal microbial transplantation (FMT) and obesity.

Purna Kashyap, MBBS, of the Mayo Clinic, Rochester, Minn., member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board, delved into the potential for donor microbiota transplant to address small bowel disorders, such as small intestinal bacterial overgrowth, and provided commentary regarding the potential – and limitations – of using FMT in functional bowel disorders such as irritable bowel syndrome (IBS).

Obesity

Dr. Kelly noted that two abstracts at the conference presented data about FMT in obesity. The first study was presented by Jessica Allegretti, MD, a gastroenterologist at Brigham and Women’s Hospital, Boston; the second study was presented by Elaine Yu, MD, an endocrinologist at Massachusetts General Hospital, Boston.

The two studies shared some similarities, but had some differences, said Dr. Kelly. “They both used lean donor encapsulated FMT ... and they both were placebo controlled, using placebo capsules.” The first study looked at metabolically healthy obese patients, while the second study included patients with mild to moderate insulin resistance.

Dr. Allegretti’s work looked at the effect that FMT from lean donors had on levels of a satiety peptide, glucagonlike peptide–1 (GLP-1), while also looking at changes in weight and microbiota, as well as safety. Patients received an initial 30-capsule dose as well as two later doses of 12 capsules each. The 22-patient study, in which individuals were randomized 1:1 to FMT or placebo capsules, didn’t show statistically significant changes in GLP-1 levels or body mass index with FMT over the 12-week study period. “But they were able to show engraftment, which I think is an important thing that you do wonder about – over this period of time, the bacteria that came from the lean donor actually engrafted into the recipient and affected the diversity. The recipient became more similar to the donor,” said Dr. Kelly.

There were some clues among the findings that engraftment was effecting metabolic change in the recipient, she said, including differences in bile acid conversion among gut bacteria; also, lower levels of the primary bile acid taurocholic acid in recipients after FMT. “So it was a negative study in what she was looking for, but an example of these smaller studies kind of pushing the field along.”

In discussing the study presented by Dr. Yu that examined lean donor FMT in individuals with insulin resistance, Dr. Kelly said, “It was actually pretty sophisticated.” By using hyperinsulinemic euglycemic clamping, the investigators were able to measure insulin sensitivity based on glucose load. In this study of 24 individuals randomized 1:1 to receive FMT or placebo capsules, recipients received weekly doses over a period of 6 weeks. Here again, though Dr. Yu and colleagues again found engraftment, “they did not find the big changes in metabolic parameters that they hoped that they would,” said Dr. Kelly.

These two studies furthered previous work completed in the Netherlands examining lean donor FMT for individuals with metabolic syndrome. “Those [studies] did show both engraftment and some changes in insulin resistance,” but they were also small studies, noted Dr. Kelly. Dr. Kashyap pointed out that the earlier studies had shown in a subgroup analysis that response to FMT was limited to those patients who lacked microbial diversity pretransplant.

This makes some mechanistic sense when thinking about FMT’s greatest success to date: Treating Clostridioides difficile infection, a condition whose very hallmark is dysbiosis characterized by monospecies gut domination, noted Dr. Kashyap.

Added Dr. Kelly, “I think everyone’s hoping there’s going to be this pill that’s going to make us skinny, but I don’t think we’re going to find that with FMT and obesity. I do think these studies are important, because there’s so much animal data already, and we’re kind of like, ‘How much more can you do in mice?’ ” By translating this preclinical work into humans, the mechanisms of obesity and the role of the microbiome can be better understood.

IBS

Turning to functional bowel disorders, Dr. Kelly pointed out a new study examining FMT for IBS. “So far, the research has been pretty disappointing,” she noted. The study, presented by Prashant Singh, MBBS, a gastroenterology fellow at Beth Israel Deaconess Medical Center, Boston, examined FMT for patients with moderate to severe diarrhea-predominant IBS. The study had four arms, randomizing the 44 participants to FMT alone; pretreatment with metronidazole and ciprofloxacin or rifaximin, each followed by FMT; or placebo. “It really didn’t show any differences in their severity of IBS in any group; so no effect: a negative study,” said Dr. Kelly.

“It’s challenging. FMT is an appealing strategy because we don’t have to put a lot of thought process into it,” said Dr. Kashyap, but it’s no panacea. “We aren’t going to be able to treat everybody with FMT.

“The challenge with IBS is that if we look at all the compositional studies, the majority of them show that at least a big subset of patients with IBS already have a normal-appearing microbiome,” said Dr. Kashyap. In those patients, “It’s very hard to know what FMT is doing.” He noted that IBS subclassifications are made by pathophysiology, without regard to the intestinal microbiome, so these classifications may not be useful for determining who may benefit from FMT.

“Again, there’s always an opportunity to learn from these studies,” whether they’re positive or negative, as long as they’re well done, said Dr. Kashyap. “There’s always an opportunity to go back and see, was there a specific subgroup of patients who responded, where there might be one or more causes which might be more amenable” to FMT.

Small intestine

And most intestinal microbial research to date, noted Dr. Kelly, has focused on the colon. “Most of our knowledge is of fecal microbiota.” New techniques including double-balloon enteroscopy of the small bowel have promise to “provide completely new information about patterns of bacteria throughout the small bowel,” and of the role of small bowel bacteria in overall gut health, she said.

“The role of the small bowel has been ignored because of accessibility,” agreed Dr. Kashyap. There’s a current focus on research into enteroscopy and other techniques to sample small intestine microbiota, he said.

In a podium presentation, Eugene Chang, MD, Martin Boyer Professor in the University of Chicago’s department of medicine, gave a broad overview of how the small intestine microbiome modulates lipid regulation. This choice of topic for the Charles M. Mansbach Memorial Lecture shows that gastroenterologists are recognizing the importance of microbiome along the entire span of the gut, said Dr. Kashyap. Dr. Chang’s approach, he added, represents a departure in that “it’s not simply just looking at what’s present and what’s not, but seeing what’s functionally relevant to metabolism.”

“We always have known that the small intestine is the workhorse; that’s where everything happens” in terms of motility, absorption, and digestion, said Dr. Kashyap. “But because of our inability to reach it easily we’ve always chosen to ignore it; we always go after the low-hanging fruit.” Despite challenges, more microbiome research should be small-bowel focused. “Eventually, it’s no pain, no gain.”

Dr. Kashyap is on the advisory board of uBiome, and is an ad hoc advisory board member for Salix Pharmaceuticals. Dr. Kelly reported no conflicts of interest.

This story was updated on July 30, 2019.

[email protected]

Clinical question: Among older adults, what attitudes exist toward deprescribing?

Background: Polypharmacy in older adults is common and can be associated with increased hospitalizations and reduced quality of life.

Study design: Population-based survey study.

Setting: Medicare beneficiaries in the United States.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Among older adults, what attitudes exist toward deprescribing?

Background: Polypharmacy in older adults is common and can be associated with increased hospitalizations and reduced quality of life.

Study design: Population-based survey study.

Setting: Medicare beneficiaries in the United States.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

Clinical question: Among older adults, what attitudes exist toward deprescribing?

Background: Polypharmacy in older adults is common and can be associated with increased hospitalizations and reduced quality of life.

Study design: Population-based survey study.

Setting: Medicare beneficiaries in the United States.

Dr. Stanley is assistant professor of medicine at Northwestern University Feinberg School of Medicine and a hospitalist at Northwestern Memorial Hospital, both in Chicago.

NEW YORK – Clinicians should resist the temptation to use untrained interpreters, such as a child, another relative, or their own limited language skills, when treating patients who cannot communicate in English, according to an expert reviewing this issue at the American Academy of Dermatology summer meeting.

In clinical encounters with patients who have limited English proficiency, “it is both our legal and our ethical responsibility to communicate through qualified interpreters,” reported Amy Y.Y. Chen, MD, who is affiliated with Central Connecticut Dermatology in Canton.

In many situations, interpreter services are required by law. This includes a provision of the 1963 Civil Rights Act that specifies these services should be made available to any individual with limited English proficiency receiving federal financial assistance (with the exception of Medicare Part B).

In reviewing this and other laws, Dr. Chen explained that many prohibitions are explicit. For example, it is against the law for clinicians to communicate with the patient through children, whether or not they are related to the patient. A patient’s adult companions are also prohibited from interpreting unless the patient has provided express permission.

Despite the rules, some clinicians might be tempted to forgo a translator when none is readily available, opting for an improvised solution. Dr. Chen said that this is ill advised even when it is not illegal.

“There are a lot of potential problems with using nonprofessional interpreters, starting with the issue of confidentiality,” Dr. Chen warned.

As defined by the Department of Health & Human Services, a qualified interpreter establishes competency by developing familiarity with specialized terminology; by communicating accurately, effectively, and impartially; and by recognizing the ethical issues, including confidentiality, essential to their role.

By itself, language fluency might not be sufficient. Many physicians have conversational fluency in one or more languages other than English, but Dr. Chen pointed out that complex and nuanced clinical descriptions might be difficult to follow for a nonnative speaker. Moreover, many individuals who have no problem posing questions in a foreign language don’t do nearly as well in following the answers.

As interpreters, family members can be particularly problematic. In addition to the issues of confidentiality and medical terminology, a family member might have his or her own agenda that influences how questions and answers are conveyed.

Moreover, family members and others untrained in translating might edit answers based on their own sense of relevance. Many clinicians working through an interpreter will recognize the experience of receiving a yes or no answer after a lengthy discussion between a nontrained interpreter and patient. In such situations, the clinician can reasonably worry that important information was lost.

Typically, major hospitals already offer a systematic approach to providing interpreters when needed, but physicians working in private practice or other smaller practice settings might not. According to Dr. Chen, who recently collaborated on review of this issue (J Am Acad Dermatol. 2019 Mar;80:829-31), they should.

Interpreter services are available by telephone or Internet. Fees typically fall in the range of $2-$5 per minute. In offices with bilingual staff members, formal medical interpreter training might make sense. The Certification Commission for Healthcare Interpreters and the National Board of Certification for Medical Interpreters can help in this process.

When using a medical interpreter, Dr. Chen had some tips.

“Maintain eye contact and talk to the patient,” said Dr. Chen, suggesting that the interpreter, if present in the room, be seated next to or behind the patient. Whether the interpreter is in the room or participating remotely, Dr. Chen advised against speaking through the interpreter with such phases as “tell her that.” Rather, she advised speaking directly to the patient with the interpreter providing the translation.

More practically, Dr. Chen recommended speaking slowly and posing only one question at a time. She also recommended strategies to elicit reassurance that the patient has understood what was communicated. Not least, she recommended a “show me” approach in which a patient can repeat or demonstrate what he or she has learned.

Citing evidence that poor and incomplete translation contributes to medical errors and patient dissatisfaction, Dr. Chen reiterated that engaging unbiased trained translators is advisable for good clinical care even if it were not mandated by law.

NEW YORK – Clinicians should resist the temptation to use untrained interpreters, such as a child, another relative, or their own limited language skills, when treating patients who cannot communicate in English, according to an expert reviewing this issue at the American Academy of Dermatology summer meeting.

In clinical encounters with patients who have limited English proficiency, “it is both our legal and our ethical responsibility to communicate through qualified interpreters,” reported Amy Y.Y. Chen, MD, who is affiliated with Central Connecticut Dermatology in Canton.

In many situations, interpreter services are required by law. This includes a provision of the 1963 Civil Rights Act that specifies these services should be made available to any individual with limited English proficiency receiving federal financial assistance (with the exception of Medicare Part B).

In reviewing this and other laws, Dr. Chen explained that many prohibitions are explicit. For example, it is against the law for clinicians to communicate with the patient through children, whether or not they are related to the patient. A patient’s adult companions are also prohibited from interpreting unless the patient has provided express permission.

Despite the rules, some clinicians might be tempted to forgo a translator when none is readily available, opting for an improvised solution. Dr. Chen said that this is ill advised even when it is not illegal.

“There are a lot of potential problems with using nonprofessional interpreters, starting with the issue of confidentiality,” Dr. Chen warned.

As defined by the Department of Health & Human Services, a qualified interpreter establishes competency by developing familiarity with specialized terminology; by communicating accurately, effectively, and impartially; and by recognizing the ethical issues, including confidentiality, essential to their role.

By itself, language fluency might not be sufficient. Many physicians have conversational fluency in one or more languages other than English, but Dr. Chen pointed out that complex and nuanced clinical descriptions might be difficult to follow for a nonnative speaker. Moreover, many individuals who have no problem posing questions in a foreign language don’t do nearly as well in following the answers.

As interpreters, family members can be particularly problematic. In addition to the issues of confidentiality and medical terminology, a family member might have his or her own agenda that influences how questions and answers are conveyed.

Moreover, family members and others untrained in translating might edit answers based on their own sense of relevance. Many clinicians working through an interpreter will recognize the experience of receiving a yes or no answer after a lengthy discussion between a nontrained interpreter and patient. In such situations, the clinician can reasonably worry that important information was lost.

Typically, major hospitals already offer a systematic approach to providing interpreters when needed, but physicians working in private practice or other smaller practice settings might not. According to Dr. Chen, who recently collaborated on review of this issue (J Am Acad Dermatol. 2019 Mar;80:829-31), they should.

Interpreter services are available by telephone or Internet. Fees typically fall in the range of $2-$5 per minute. In offices with bilingual staff members, formal medical interpreter training might make sense. The Certification Commission for Healthcare Interpreters and the National Board of Certification for Medical Interpreters can help in this process.

When using a medical interpreter, Dr. Chen had some tips.

“Maintain eye contact and talk to the patient,” said Dr. Chen, suggesting that the interpreter, if present in the room, be seated next to or behind the patient. Whether the interpreter is in the room or participating remotely, Dr. Chen advised against speaking through the interpreter with such phases as “tell her that.” Rather, she advised speaking directly to the patient with the interpreter providing the translation.

More practically, Dr. Chen recommended speaking slowly and posing only one question at a time. She also recommended strategies to elicit reassurance that the patient has understood what was communicated. Not least, she recommended a “show me” approach in which a patient can repeat or demonstrate what he or she has learned.

Citing evidence that poor and incomplete translation contributes to medical errors and patient dissatisfaction, Dr. Chen reiterated that engaging unbiased trained translators is advisable for good clinical care even if it were not mandated by law.

NEW YORK – Clinicians should resist the temptation to use untrained interpreters, such as a child, another relative, or their own limited language skills, when treating patients who cannot communicate in English, according to an expert reviewing this issue at the American Academy of Dermatology summer meeting.

In clinical encounters with patients who have limited English proficiency, “it is both our legal and our ethical responsibility to communicate through qualified interpreters,” reported Amy Y.Y. Chen, MD, who is affiliated with Central Connecticut Dermatology in Canton.

In many situations, interpreter services are required by law. This includes a provision of the 1963 Civil Rights Act that specifies these services should be made available to any individual with limited English proficiency receiving federal financial assistance (with the exception of Medicare Part B).

In reviewing this and other laws, Dr. Chen explained that many prohibitions are explicit. For example, it is against the law for clinicians to communicate with the patient through children, whether or not they are related to the patient. A patient’s adult companions are also prohibited from interpreting unless the patient has provided express permission.

Despite the rules, some clinicians might be tempted to forgo a translator when none is readily available, opting for an improvised solution. Dr. Chen said that this is ill advised even when it is not illegal.

“There are a lot of potential problems with using nonprofessional interpreters, starting with the issue of confidentiality,” Dr. Chen warned.

As defined by the Department of Health & Human Services, a qualified interpreter establishes competency by developing familiarity with specialized terminology; by communicating accurately, effectively, and impartially; and by recognizing the ethical issues, including confidentiality, essential to their role.

By itself, language fluency might not be sufficient. Many physicians have conversational fluency in one or more languages other than English, but Dr. Chen pointed out that complex and nuanced clinical descriptions might be difficult to follow for a nonnative speaker. Moreover, many individuals who have no problem posing questions in a foreign language don’t do nearly as well in following the answers.

As interpreters, family members can be particularly problematic. In addition to the issues of confidentiality and medical terminology, a family member might have his or her own agenda that influences how questions and answers are conveyed.

Moreover, family members and others untrained in translating might edit answers based on their own sense of relevance. Many clinicians working through an interpreter will recognize the experience of receiving a yes or no answer after a lengthy discussion between a nontrained interpreter and patient. In such situations, the clinician can reasonably worry that important information was lost.

Typically, major hospitals already offer a systematic approach to providing interpreters when needed, but physicians working in private practice or other smaller practice settings might not. According to Dr. Chen, who recently collaborated on review of this issue (J Am Acad Dermatol. 2019 Mar;80:829-31), they should.

Interpreter services are available by telephone or Internet. Fees typically fall in the range of $2-$5 per minute. In offices with bilingual staff members, formal medical interpreter training might make sense. The Certification Commission for Healthcare Interpreters and the National Board of Certification for Medical Interpreters can help in this process.

When using a medical interpreter, Dr. Chen had some tips.

“Maintain eye contact and talk to the patient,” said Dr. Chen, suggesting that the interpreter, if present in the room, be seated next to or behind the patient. Whether the interpreter is in the room or participating remotely, Dr. Chen advised against speaking through the interpreter with such phases as “tell her that.” Rather, she advised speaking directly to the patient with the interpreter providing the translation.

More practically, Dr. Chen recommended speaking slowly and posing only one question at a time. She also recommended strategies to elicit reassurance that the patient has understood what was communicated. Not least, she recommended a “show me” approach in which a patient can repeat or demonstrate what he or she has learned.

Citing evidence that poor and incomplete translation contributes to medical errors and patient dissatisfaction, Dr. Chen reiterated that engaging unbiased trained translators is advisable for good clinical care even if it were not mandated by law.

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

TORONTO – Emerging evidence indicates that patients with knee osteoarthritis who engage in high-intensity interval training obtain significantly greater improvement in physical function than with conventionally prescribed moderate-intensity exercise, Monica R. Maly, PhD, said at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

This was one of the key conclusions she and her coworkers drew from their analysis of the past year’s published research on diet and exercise interventions to improve outcomes in patients with OA, where obesity and physical inactivity figure prominently as modifiable lifestyle factors.

Another finding: Exercise interventions are where all the action is at present in the field of lifestyle-modification research aimed at achieving better health-related quality of life and other positive outcomes in OA. Dietary interventions are simply not a hot research topic. Indeed, her review of the past year’s literature included 38 randomized, controlled trials (RCTs) and 15 meta-analyses and systematic reviews – and all 38 RCTs addressed exercise interventions.

“It’s interesting to note that we found no new RCT data on diet to modify obesity in OA in the past year,” Dr. Maly said at the meeting sponsored by the Osteoarthritis Research Society International.

Additionally, 32 of the 38 RCTs devoted to exercise interventions for OA focused specifically on knee OA, noted Dr. Maly of the department of kinesiology at the University of Waterloo (Ont.).

Aerobic exercise dosage and intensity

Australian investigators conducted a pilot randomized trial of high-intensity interval training (HIIT) versus more conventional moderate-intensity exercise to improve health-related quality of life and physical function in 27 patients with knee OA. The exercise programs involved unsupervised home-based cycling, with participants requested to do four roughly 25-minute sessions per week for 8 weeks.

The two exercise intensity groups showed similar gains in health-related quality of life as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). However, the HIIT group showed significantly greater improvement in physical function as measured on the Timed Up and Go test (PeerJ. 2018 May 9;6:e4738).

Dr. Maly noted that adherence to the home-based exercise programs was a challenge: Only 17 of the 27 patients completed the 8-week Australian study, for a 37% dropout rate. However, most study withdrawals were because of family-related issues, illness, or injuries unrelated to cycling, with no signal that HIIT placed knee OA patients at higher injury risk.

Other investigators performed a systematic review of 45 studies in an effort to generate evidence-based guidance about the optimal exercise dosing in order to improve outcomes in knee OA patients. They concluded that programs comprising 24 therapeutic exercise sessions over the course of 8-12 weeks resulted in the largest improvements in measures of pain and physical function. And, importantly, one exercise session per week conferred no benefits (J Orthop Sports Phys Ther. 2018 Mar;48[3]:146-61).

“Frequency probably matters,” Dr. Maly observed.

Patients and their physicians often wonder if long-term, land-based exercise might have deleterious impacts on joint structure in patients with knee OA. Reassurance on this score was provided by a recent meta-analysis of RCTs that concluded, on the basis of moderate-strength evidence, that exercise therapy of longer than 6 months duration had no adverse effect on tibiofemoral radiographic disease severity, compared with no exercise. Nor was there evidence of a long-term-exercise–associated deterioration of tibiofemoral cartilage morphology or worsening of synovitis or effusion. Plus, the meta-analysis provided limited evidence to suggest long-term exercise had a protective effect on the composition of patellar cartilage (Semin Arthritis Rheum. 2019 Jun;48[6]:941-9).

“While there was a little bit of evidence suggesting that long-term exercise could worsen bone marrow lesions, really there was no other evidence that it could change the structure of a joint,” according to Dr. Maly.

Internet-based exercise training

Using the Internet to deliver an individually tailored exercise-training program for patients with symptomatic knee OA might sound like an efficient strategy, but in fact it proved fruitless in a large randomized trial. The 350 participants were assigned to an 8-visit, 4-month program of physical therapy, a wait-list control group, or an internet-based program that delivered tailored exercises and video demonstrations with no face-to-face contact. The bottom line is that improvement in WOMAC scores didn’t differ significantly between the three groups when evaluated at 4 and 12 months (Osteoarthritis Cartilage. 2018 Mar;26[3]:383-96).

“When we deliver exercise with the use of technology, it may require some support, including face to face,” Dr. Maly concluded from the study results.

Strength training

High-intensity resistance training such as weight lifting aimed at strengthening the quadriceps and other large muscles is often eschewed in patients with knee OA because of concern about possible damage to their already damaged joints. Intriguingly, Brazilian investigators may have found a workaround. They randomized 48 women with knee OA to 12 weeks of either supervised low-intensity resistance training performed with partial blood-flow restriction using an air cuff, to low-intensity resistance training alone, or to high-intensity resistance training. The low-intensity resistance workouts involved exercises such as leg presses and knee extensions performed at 30% of maximum effort.

The low-intensity resistance training performed with blood-flow restriction and the high-intensity strength training programs proved similarly effective in improving quadriceps muscle mass, muscle strength, and physical function to a significantly greater extent than with low-intensity resistance training alone. Moreover, low-intensity resistance training with blood-flow restriction also resulted in a significant improvement in pain scores. That finding, coupled with the fact that 4 of the 16 patients in the high-intensity resistance training group dropped out of the trial because of exercise-induced knee pain, suggests that low-intensity strength training carried out with partial blood-flow restriction may have a bright future (Med Sci Sports Exerc. 2018 May;50[5]:897-905).

Exercise plus diet-induced weight loss

How does the combination of dietary weight loss plus exercise stack up against diet alone in terms of benefits on pain and physical function in obese patients with knee OA? A systematic review and meta-analysis of nine RCTs aimed at answering that question concluded that diet-alone strategies are less effective. Both the diet-plus-exercise and diet-only interventions resulted in comparably moderate improvement in physical function. However, diet-only treatments didn’t reduce pain, whereas diet-plus-exercise interventions achieved moderate pain relief (Semin Arthritis Rheum. 2019 Apr;48[5]:765-77).

Dr. Maly reported having no financial conflicts of interest regarding her presentation.

[email protected]

TORONTO – Emerging evidence indicates that patients with knee osteoarthritis who engage in high-intensity interval training obtain significantly greater improvement in physical function than with conventionally prescribed moderate-intensity exercise, Monica R. Maly, PhD, said at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

This was one of the key conclusions she and her coworkers drew from their analysis of the past year’s published research on diet and exercise interventions to improve outcomes in patients with OA, where obesity and physical inactivity figure prominently as modifiable lifestyle factors.

Another finding: Exercise interventions are where all the action is at present in the field of lifestyle-modification research aimed at achieving better health-related quality of life and other positive outcomes in OA. Dietary interventions are simply not a hot research topic. Indeed, her review of the past year’s literature included 38 randomized, controlled trials (RCTs) and 15 meta-analyses and systematic reviews – and all 38 RCTs addressed exercise interventions.

“It’s interesting to note that we found no new RCT data on diet to modify obesity in OA in the past year,” Dr. Maly said at the meeting sponsored by the Osteoarthritis Research Society International.

Additionally, 32 of the 38 RCTs devoted to exercise interventions for OA focused specifically on knee OA, noted Dr. Maly of the department of kinesiology at the University of Waterloo (Ont.).

Aerobic exercise dosage and intensity

Australian investigators conducted a pilot randomized trial of high-intensity interval training (HIIT) versus more conventional moderate-intensity exercise to improve health-related quality of life and physical function in 27 patients with knee OA. The exercise programs involved unsupervised home-based cycling, with participants requested to do four roughly 25-minute sessions per week for 8 weeks.

The two exercise intensity groups showed similar gains in health-related quality of life as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). However, the HIIT group showed significantly greater improvement in physical function as measured on the Timed Up and Go test (PeerJ. 2018 May 9;6:e4738).

Dr. Maly noted that adherence to the home-based exercise programs was a challenge: Only 17 of the 27 patients completed the 8-week Australian study, for a 37% dropout rate. However, most study withdrawals were because of family-related issues, illness, or injuries unrelated to cycling, with no signal that HIIT placed knee OA patients at higher injury risk.

Other investigators performed a systematic review of 45 studies in an effort to generate evidence-based guidance about the optimal exercise dosing in order to improve outcomes in knee OA patients. They concluded that programs comprising 24 therapeutic exercise sessions over the course of 8-12 weeks resulted in the largest improvements in measures of pain and physical function. And, importantly, one exercise session per week conferred no benefits (J Orthop Sports Phys Ther. 2018 Mar;48[3]:146-61).

“Frequency probably matters,” Dr. Maly observed.

Patients and their physicians often wonder if long-term, land-based exercise might have deleterious impacts on joint structure in patients with knee OA. Reassurance on this score was provided by a recent meta-analysis of RCTs that concluded, on the basis of moderate-strength evidence, that exercise therapy of longer than 6 months duration had no adverse effect on tibiofemoral radiographic disease severity, compared with no exercise. Nor was there evidence of a long-term-exercise–associated deterioration of tibiofemoral cartilage morphology or worsening of synovitis or effusion. Plus, the meta-analysis provided limited evidence to suggest long-term exercise had a protective effect on the composition of patellar cartilage (Semin Arthritis Rheum. 2019 Jun;48[6]:941-9).

“While there was a little bit of evidence suggesting that long-term exercise could worsen bone marrow lesions, really there was no other evidence that it could change the structure of a joint,” according to Dr. Maly.

Internet-based exercise training

Using the Internet to deliver an individually tailored exercise-training program for patients with symptomatic knee OA might sound like an efficient strategy, but in fact it proved fruitless in a large randomized trial. The 350 participants were assigned to an 8-visit, 4-month program of physical therapy, a wait-list control group, or an internet-based program that delivered tailored exercises and video demonstrations with no face-to-face contact. The bottom line is that improvement in WOMAC scores didn’t differ significantly between the three groups when evaluated at 4 and 12 months (Osteoarthritis Cartilage. 2018 Mar;26[3]:383-96).

“When we deliver exercise with the use of technology, it may require some support, including face to face,” Dr. Maly concluded from the study results.

Strength training

High-intensity resistance training such as weight lifting aimed at strengthening the quadriceps and other large muscles is often eschewed in patients with knee OA because of concern about possible damage to their already damaged joints. Intriguingly, Brazilian investigators may have found a workaround. They randomized 48 women with knee OA to 12 weeks of either supervised low-intensity resistance training performed with partial blood-flow restriction using an air cuff, to low-intensity resistance training alone, or to high-intensity resistance training. The low-intensity resistance workouts involved exercises such as leg presses and knee extensions performed at 30% of maximum effort.

The low-intensity resistance training performed with blood-flow restriction and the high-intensity strength training programs proved similarly effective in improving quadriceps muscle mass, muscle strength, and physical function to a significantly greater extent than with low-intensity resistance training alone. Moreover, low-intensity resistance training with blood-flow restriction also resulted in a significant improvement in pain scores. That finding, coupled with the fact that 4 of the 16 patients in the high-intensity resistance training group dropped out of the trial because of exercise-induced knee pain, suggests that low-intensity strength training carried out with partial blood-flow restriction may have a bright future (Med Sci Sports Exerc. 2018 May;50[5]:897-905).

Exercise plus diet-induced weight loss

How does the combination of dietary weight loss plus exercise stack up against diet alone in terms of benefits on pain and physical function in obese patients with knee OA? A systematic review and meta-analysis of nine RCTs aimed at answering that question concluded that diet-alone strategies are less effective. Both the diet-plus-exercise and diet-only interventions resulted in comparably moderate improvement in physical function. However, diet-only treatments didn’t reduce pain, whereas diet-plus-exercise interventions achieved moderate pain relief (Semin Arthritis Rheum. 2019 Apr;48[5]:765-77).

Dr. Maly reported having no financial conflicts of interest regarding her presentation.

[email protected]

TORONTO – Emerging evidence indicates that patients with knee osteoarthritis who engage in high-intensity interval training obtain significantly greater improvement in physical function than with conventionally prescribed moderate-intensity exercise, Monica R. Maly, PhD, said at the OARSI 2019 World Congress.

Bruce Jancin/MDedge News

This was one of the key conclusions she and her coworkers drew from their analysis of the past year’s published research on diet and exercise interventions to improve outcomes in patients with OA, where obesity and physical inactivity figure prominently as modifiable lifestyle factors.

Another finding: Exercise interventions are where all the action is at present in the field of lifestyle-modification research aimed at achieving better health-related quality of life and other positive outcomes in OA. Dietary interventions are simply not a hot research topic. Indeed, her review of the past year’s literature included 38 randomized, controlled trials (RCTs) and 15 meta-analyses and systematic reviews – and all 38 RCTs addressed exercise interventions.

“It’s interesting to note that we found no new RCT data on diet to modify obesity in OA in the past year,” Dr. Maly said at the meeting sponsored by the Osteoarthritis Research Society International.

Additionally, 32 of the 38 RCTs devoted to exercise interventions for OA focused specifically on knee OA, noted Dr. Maly of the department of kinesiology at the University of Waterloo (Ont.).

Aerobic exercise dosage and intensity

Australian investigators conducted a pilot randomized trial of high-intensity interval training (HIIT) versus more conventional moderate-intensity exercise to improve health-related quality of life and physical function in 27 patients with knee OA. The exercise programs involved unsupervised home-based cycling, with participants requested to do four roughly 25-minute sessions per week for 8 weeks.

The two exercise intensity groups showed similar gains in health-related quality of life as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). However, the HIIT group showed significantly greater improvement in physical function as measured on the Timed Up and Go test (PeerJ. 2018 May 9;6:e4738).

Dr. Maly noted that adherence to the home-based exercise programs was a challenge: Only 17 of the 27 patients completed the 8-week Australian study, for a 37% dropout rate. However, most study withdrawals were because of family-related issues, illness, or injuries unrelated to cycling, with no signal that HIIT placed knee OA patients at higher injury risk.

Other investigators performed a systematic review of 45 studies in an effort to generate evidence-based guidance about the optimal exercise dosing in order to improve outcomes in knee OA patients. They concluded that programs comprising 24 therapeutic exercise sessions over the course of 8-12 weeks resulted in the largest improvements in measures of pain and physical function. And, importantly, one exercise session per week conferred no benefits (J Orthop Sports Phys Ther. 2018 Mar;48[3]:146-61).

“Frequency probably matters,” Dr. Maly observed.

Patients and their physicians often wonder if long-term, land-based exercise might have deleterious impacts on joint structure in patients with knee OA. Reassurance on this score was provided by a recent meta-analysis of RCTs that concluded, on the basis of moderate-strength evidence, that exercise therapy of longer than 6 months duration had no adverse effect on tibiofemoral radiographic disease severity, compared with no exercise. Nor was there evidence of a long-term-exercise–associated deterioration of tibiofemoral cartilage morphology or worsening of synovitis or effusion. Plus, the meta-analysis provided limited evidence to suggest long-term exercise had a protective effect on the composition of patellar cartilage (Semin Arthritis Rheum. 2019 Jun;48[6]:941-9).

“While there was a little bit of evidence suggesting that long-term exercise could worsen bone marrow lesions, really there was no other evidence that it could change the structure of a joint,” according to Dr. Maly.

Internet-based exercise training

Using the Internet to deliver an individually tailored exercise-training program for patients with symptomatic knee OA might sound like an efficient strategy, but in fact it proved fruitless in a large randomized trial. The 350 participants were assigned to an 8-visit, 4-month program of physical therapy, a wait-list control group, or an internet-based program that delivered tailored exercises and video demonstrations with no face-to-face contact. The bottom line is that improvement in WOMAC scores didn’t differ significantly between the three groups when evaluated at 4 and 12 months (Osteoarthritis Cartilage. 2018 Mar;26[3]:383-96).

“When we deliver exercise with the use of technology, it may require some support, including face to face,” Dr. Maly concluded from the study results.

Strength training

High-intensity resistance training such as weight lifting aimed at strengthening the quadriceps and other large muscles is often eschewed in patients with knee OA because of concern about possible damage to their already damaged joints. Intriguingly, Brazilian investigators may have found a workaround. They randomized 48 women with knee OA to 12 weeks of either supervised low-intensity resistance training performed with partial blood-flow restriction using an air cuff, to low-intensity resistance training alone, or to high-intensity resistance training. The low-intensity resistance workouts involved exercises such as leg presses and knee extensions performed at 30% of maximum effort.

The low-intensity resistance training performed with blood-flow restriction and the high-intensity strength training programs proved similarly effective in improving quadriceps muscle mass, muscle strength, and physical function to a significantly greater extent than with low-intensity resistance training alone. Moreover, low-intensity resistance training with blood-flow restriction also resulted in a significant improvement in pain scores. That finding, coupled with the fact that 4 of the 16 patients in the high-intensity resistance training group dropped out of the trial because of exercise-induced knee pain, suggests that low-intensity strength training carried out with partial blood-flow restriction may have a bright future (Med Sci Sports Exerc. 2018 May;50[5]:897-905).

Exercise plus diet-induced weight loss

How does the combination of dietary weight loss plus exercise stack up against diet alone in terms of benefits on pain and physical function in obese patients with knee OA? A systematic review and meta-analysis of nine RCTs aimed at answering that question concluded that diet-alone strategies are less effective. Both the diet-plus-exercise and diet-only interventions resulted in comparably moderate improvement in physical function. However, diet-only treatments didn’t reduce pain, whereas diet-plus-exercise interventions achieved moderate pain relief (Semin Arthritis Rheum. 2019 Apr;48[5]:765-77).

Dr. Maly reported having no financial conflicts of interest regarding her presentation.

[email protected]

A patient treated with immune checkpoint inhibitor therapy for thyroid carcinoma presented with lichenoid dermatitis that resembled mycosis fungoides and also showed with monoclonal T-cell receptor gene rearrangement.

A case report published in the Journal of Cutaneous Pathology describes the “unusual” case and highlights another form of lichenoid dermatitis that may occur with immune checkpoint inhibitor therapy.

The patient was a 66-year-old man with BRAF_V600E-mutated anaplastic thyroid carcinoma, who was enrolled in a clinical trial of the checkpoint inhibitor atezolizumab, in combination with the BRAF inhibitor vemurafenib and MEK inhibitor cobimetinib.

Around 11 months after starting treatment, he presented to a dermatology department with a 1.5-cm x 1.2-cm crusted, erythematous plaque on his abdomen that had appeared 3 weeks earlier. He also had several follicular-based erythematous papules on his extremities and a single verrucous papule on his index finger, which the authors wrote were likely associated with the vemurafenib therapy.

The patient had previously had a squamous cell carcinoma removed but had no history of cutaneous lymphoma.

A punch biopsy of the abdominal lesion showed dense lichenoid, lymphohistiocytic infiltrate with papillary dermal fibrosis, and scattered multinucleated giant histiocytes. Immunohistochemical studies showed the lesion had an abnormal immunophenotype in which CD4+ cells were four to five times more common than CD8+ cells, and there was partial loss of CD7 expression.

The lesion was treated with 0.05% clobetasol cream and monitored without interrupting the cancer therapy. The lesion gradually reduced in size, but 4 months later, another lesion appeared on the patient’s right clavicle.

A skin biopsy revealed lichenoid lymphohistiocytic infiltrate with occasional giant cells in the superficial dermis, as well as atypical, hyperchromatic lymphocytes with clear halos. Immunohistochemical studies showed that the new lesion was similar to the earlier abdominal lesion.

T-cell receptor gene rearrangement studies on both lesions showed that the abdominal lesion had both monoclonal TCR-gamma and TCR-beta gene rearrangements. The clavicle lesion showed the same monoclonal TCR-gamma rearrangement as the abdominal lesion, but lacked the TCR-beta gene rearrangement.

The lesions continued to be treated with clobetasol cream (0.05%), and the patient remained on the anticancer treatment regimen.

Michael T. Tetzlaff, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote that up to half of all patients treated with immune checkpoint inhibitors develop some kind of cutaneous immune-related adverse event, and lichenoid dermatitis is one of the most common seen in biopsies.

“Clinical and pathological recognition of monoclonal [lichenoid dermatitis associated with immune checkpoint inhibitors] in the context of [immune checkpoint inhibitor] therapy will be important for accurate diagnosis and patient care,” they wrote.

The researchers did not report financial disclosures.

SOURCE: Tetzlaff MT et al. J Cutan Pathol. 2019 Jun 29. doi: 10.1111/cup.13536.

A patient treated with immune checkpoint inhibitor therapy for thyroid carcinoma presented with lichenoid dermatitis that resembled mycosis fungoides and also showed with monoclonal T-cell receptor gene rearrangement.

A case report published in the Journal of Cutaneous Pathology describes the “unusual” case and highlights another form of lichenoid dermatitis that may occur with immune checkpoint inhibitor therapy.

The patient was a 66-year-old man with BRAF_V600E-mutated anaplastic thyroid carcinoma, who was enrolled in a clinical trial of the checkpoint inhibitor atezolizumab, in combination with the BRAF inhibitor vemurafenib and MEK inhibitor cobimetinib.

Around 11 months after starting treatment, he presented to a dermatology department with a 1.5-cm x 1.2-cm crusted, erythematous plaque on his abdomen that had appeared 3 weeks earlier. He also had several follicular-based erythematous papules on his extremities and a single verrucous papule on his index finger, which the authors wrote were likely associated with the vemurafenib therapy.

The patient had previously had a squamous cell carcinoma removed but had no history of cutaneous lymphoma.

A punch biopsy of the abdominal lesion showed dense lichenoid, lymphohistiocytic infiltrate with papillary dermal fibrosis, and scattered multinucleated giant histiocytes. Immunohistochemical studies showed the lesion had an abnormal immunophenotype in which CD4+ cells were four to five times more common than CD8+ cells, and there was partial loss of CD7 expression.

The lesion was treated with 0.05% clobetasol cream and monitored without interrupting the cancer therapy. The lesion gradually reduced in size, but 4 months later, another lesion appeared on the patient’s right clavicle.

A skin biopsy revealed lichenoid lymphohistiocytic infiltrate with occasional giant cells in the superficial dermis, as well as atypical, hyperchromatic lymphocytes with clear halos. Immunohistochemical studies showed that the new lesion was similar to the earlier abdominal lesion.

T-cell receptor gene rearrangement studies on both lesions showed that the abdominal lesion had both monoclonal TCR-gamma and TCR-beta gene rearrangements. The clavicle lesion showed the same monoclonal TCR-gamma rearrangement as the abdominal lesion, but lacked the TCR-beta gene rearrangement.

The lesions continued to be treated with clobetasol cream (0.05%), and the patient remained on the anticancer treatment regimen.

Michael T. Tetzlaff, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote that up to half of all patients treated with immune checkpoint inhibitors develop some kind of cutaneous immune-related adverse event, and lichenoid dermatitis is one of the most common seen in biopsies.

“Clinical and pathological recognition of monoclonal [lichenoid dermatitis associated with immune checkpoint inhibitors] in the context of [immune checkpoint inhibitor] therapy will be important for accurate diagnosis and patient care,” they wrote.

The researchers did not report financial disclosures.

SOURCE: Tetzlaff MT et al. J Cutan Pathol. 2019 Jun 29. doi: 10.1111/cup.13536.

A patient treated with immune checkpoint inhibitor therapy for thyroid carcinoma presented with lichenoid dermatitis that resembled mycosis fungoides and also showed with monoclonal T-cell receptor gene rearrangement.

A case report published in the Journal of Cutaneous Pathology describes the “unusual” case and highlights another form of lichenoid dermatitis that may occur with immune checkpoint inhibitor therapy.

The patient was a 66-year-old man with BRAF_V600E-mutated anaplastic thyroid carcinoma, who was enrolled in a clinical trial of the checkpoint inhibitor atezolizumab, in combination with the BRAF inhibitor vemurafenib and MEK inhibitor cobimetinib.

Around 11 months after starting treatment, he presented to a dermatology department with a 1.5-cm x 1.2-cm crusted, erythematous plaque on his abdomen that had appeared 3 weeks earlier. He also had several follicular-based erythematous papules on his extremities and a single verrucous papule on his index finger, which the authors wrote were likely associated with the vemurafenib therapy.

The patient had previously had a squamous cell carcinoma removed but had no history of cutaneous lymphoma.

A punch biopsy of the abdominal lesion showed dense lichenoid, lymphohistiocytic infiltrate with papillary dermal fibrosis, and scattered multinucleated giant histiocytes. Immunohistochemical studies showed the lesion had an abnormal immunophenotype in which CD4+ cells were four to five times more common than CD8+ cells, and there was partial loss of CD7 expression.

The lesion was treated with 0.05% clobetasol cream and monitored without interrupting the cancer therapy. The lesion gradually reduced in size, but 4 months later, another lesion appeared on the patient’s right clavicle.

A skin biopsy revealed lichenoid lymphohistiocytic infiltrate with occasional giant cells in the superficial dermis, as well as atypical, hyperchromatic lymphocytes with clear halos. Immunohistochemical studies showed that the new lesion was similar to the earlier abdominal lesion.

T-cell receptor gene rearrangement studies on both lesions showed that the abdominal lesion had both monoclonal TCR-gamma and TCR-beta gene rearrangements. The clavicle lesion showed the same monoclonal TCR-gamma rearrangement as the abdominal lesion, but lacked the TCR-beta gene rearrangement.

The lesions continued to be treated with clobetasol cream (0.05%), and the patient remained on the anticancer treatment regimen.

Michael T. Tetzlaff, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote that up to half of all patients treated with immune checkpoint inhibitors develop some kind of cutaneous immune-related adverse event, and lichenoid dermatitis is one of the most common seen in biopsies.

“Clinical and pathological recognition of monoclonal [lichenoid dermatitis associated with immune checkpoint inhibitors] in the context of [immune checkpoint inhibitor] therapy will be important for accurate diagnosis and patient care,” they wrote.

The researchers did not report financial disclosures.

SOURCE: Tetzlaff MT et al. J Cutan Pathol. 2019 Jun 29. doi: 10.1111/cup.13536.