Geriatrics

Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.

©Wavebreakmedia Ltd/thinkstockphotos.com

Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.

Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.

The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.

Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.

“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.

“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.

The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.

However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.

The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.

Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.

There was no external funding, and Dr. Sia didn’t have any disclosures.

aotto@mdedge.com

Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.

©Wavebreakmedia Ltd/thinkstockphotos.com

Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.

Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.

The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.

Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.

“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.

“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.

The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.

However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.

The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.

Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.

There was no external funding, and Dr. Sia didn’t have any disclosures.

aotto@mdedge.com

Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.

©Wavebreakmedia Ltd/thinkstockphotos.com

Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.

Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.

The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.

Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.

“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.

“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.

The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.

However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.

The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.

Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.

There was no external funding, and Dr. Sia didn’t have any disclosures.

aotto@mdedge.com

Judicious organ matching for older liver transplant candidates with hepatocellular carcinoma (HCC) leads to survival outcomes similar to those in younger recipients, a case review suggests.

Overall survival (OS) rates among transplant recipients included in a prospective institutional database were 85.5% and 84% at 3 years after liver transplant in patients aged 65 years and under and those over 65 years, respectively. The 5-year survival rates were 73.9% and 77%, respectively (P = .26), Ola Ahmed, MD, of the department of abdominal organ transplantation surgery at Washington University, St. Louis, and colleagues found.

The investigators looked at 1,629 patients diagnosed with HCC between Jan. 1, 2002, and Dec. 31, 2019 of whom 700 were considered for curative surgery, including transplant in 538, and resection in 162.

The patients had a mean age of 62.8 years. Those older than 65 years were less likely to be considered or listed for transplant (27% vs. 73%, P < .01), although oncologic staging and delisting rates were similar in both groups. “This observation still holds true after controlling for other variables, including viral hepatitis and gender in the multivariable analysis (adjusted odds ratio, 0.365),” the investigators reported in the Journal of the American College of Surgeons.

The findings were also reported at the 2020 virtual Western Surgical Association 128th Scientific Session in November.
 

The issue of resection

Surgical intervention occurred in 597 patients, including 392 and 205 aged 65 years and younger and over 65 years, respectively.

OS was lower among patients who underwent resection, compared with the liver transplant recipients, but was similar in the older and younger age groups (3-year OS, 59% vs. 64.8% and 5-year OS, 44.8% vs. 49%; P = .13). No differences were noted in the development of local or distant metastatic disease after transplant or resection.

The two age groups had comparable ICU stays (2 days) and total hospital length of stay (6 days). There were no differences in 30- and 90-day hospital readmissions, they noted.

“On additional age analysis, 65% of transplanted patients over 65 years are currently alive and were disease free at the end of the study period, compared to only 18% of their resected counterparts (P < .01),” they wrote.

Justifying transplant

The findings are notable because despite the effectiveness of transplant as an alternative treatment for unresectable HCC, older patients are often excluded from consideration for transplant. Most studies over the past 15 years have focused on patients aged under 60 years and the ability to extrapolate results to older patients has been limited. Further, results have been conflicting in older patients, the authors explained.

“This is particularly apposite at this time with prolonged life expectancy and the growing interest in improving cancer survivorship,” they noted, adding that “there is logic in challenging existing gold standards and traditional norms with real-life medical practice.

Indeed, the current findings suggest – perhaps contrary to common perceptions – that transplant in carefully selected patients “can be justified in older age groups and provide clinically meaningful and longer survival benefits,” they said, adding that “discussions should be guided by the potential for unfair age discriminations and precise terminology of physiologic rather than actual age.

“Such insights highlight the continued need for quality improvement in the surgical management of older patients, raising questions regarding current resource utilization among different age groups and how age can influence patterns of cancer care,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

Judicious organ matching for older liver transplant candidates with hepatocellular carcinoma (HCC) leads to survival outcomes similar to those in younger recipients, a case review suggests.

Overall survival (OS) rates among transplant recipients included in a prospective institutional database were 85.5% and 84% at 3 years after liver transplant in patients aged 65 years and under and those over 65 years, respectively. The 5-year survival rates were 73.9% and 77%, respectively (P = .26), Ola Ahmed, MD, of the department of abdominal organ transplantation surgery at Washington University, St. Louis, and colleagues found.

The investigators looked at 1,629 patients diagnosed with HCC between Jan. 1, 2002, and Dec. 31, 2019 of whom 700 were considered for curative surgery, including transplant in 538, and resection in 162.

The patients had a mean age of 62.8 years. Those older than 65 years were less likely to be considered or listed for transplant (27% vs. 73%, P < .01), although oncologic staging and delisting rates were similar in both groups. “This observation still holds true after controlling for other variables, including viral hepatitis and gender in the multivariable analysis (adjusted odds ratio, 0.365),” the investigators reported in the Journal of the American College of Surgeons.

The findings were also reported at the 2020 virtual Western Surgical Association 128th Scientific Session in November.
 

The issue of resection

Surgical intervention occurred in 597 patients, including 392 and 205 aged 65 years and younger and over 65 years, respectively.

OS was lower among patients who underwent resection, compared with the liver transplant recipients, but was similar in the older and younger age groups (3-year OS, 59% vs. 64.8% and 5-year OS, 44.8% vs. 49%; P = .13). No differences were noted in the development of local or distant metastatic disease after transplant or resection.

The two age groups had comparable ICU stays (2 days) and total hospital length of stay (6 days). There were no differences in 30- and 90-day hospital readmissions, they noted.

“On additional age analysis, 65% of transplanted patients over 65 years are currently alive and were disease free at the end of the study period, compared to only 18% of their resected counterparts (P < .01),” they wrote.

Justifying transplant

The findings are notable because despite the effectiveness of transplant as an alternative treatment for unresectable HCC, older patients are often excluded from consideration for transplant. Most studies over the past 15 years have focused on patients aged under 60 years and the ability to extrapolate results to older patients has been limited. Further, results have been conflicting in older patients, the authors explained.

“This is particularly apposite at this time with prolonged life expectancy and the growing interest in improving cancer survivorship,” they noted, adding that “there is logic in challenging existing gold standards and traditional norms with real-life medical practice.

Indeed, the current findings suggest – perhaps contrary to common perceptions – that transplant in carefully selected patients “can be justified in older age groups and provide clinically meaningful and longer survival benefits,” they said, adding that “discussions should be guided by the potential for unfair age discriminations and precise terminology of physiologic rather than actual age.

“Such insights highlight the continued need for quality improvement in the surgical management of older patients, raising questions regarding current resource utilization among different age groups and how age can influence patterns of cancer care,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

Judicious organ matching for older liver transplant candidates with hepatocellular carcinoma (HCC) leads to survival outcomes similar to those in younger recipients, a case review suggests.

Overall survival (OS) rates among transplant recipients included in a prospective institutional database were 85.5% and 84% at 3 years after liver transplant in patients aged 65 years and under and those over 65 years, respectively. The 5-year survival rates were 73.9% and 77%, respectively (P = .26), Ola Ahmed, MD, of the department of abdominal organ transplantation surgery at Washington University, St. Louis, and colleagues found.

The investigators looked at 1,629 patients diagnosed with HCC between Jan. 1, 2002, and Dec. 31, 2019 of whom 700 were considered for curative surgery, including transplant in 538, and resection in 162.

The patients had a mean age of 62.8 years. Those older than 65 years were less likely to be considered or listed for transplant (27% vs. 73%, P < .01), although oncologic staging and delisting rates were similar in both groups. “This observation still holds true after controlling for other variables, including viral hepatitis and gender in the multivariable analysis (adjusted odds ratio, 0.365),” the investigators reported in the Journal of the American College of Surgeons.

The findings were also reported at the 2020 virtual Western Surgical Association 128th Scientific Session in November.
 

The issue of resection

Surgical intervention occurred in 597 patients, including 392 and 205 aged 65 years and younger and over 65 years, respectively.

OS was lower among patients who underwent resection, compared with the liver transplant recipients, but was similar in the older and younger age groups (3-year OS, 59% vs. 64.8% and 5-year OS, 44.8% vs. 49%; P = .13). No differences were noted in the development of local or distant metastatic disease after transplant or resection.

The two age groups had comparable ICU stays (2 days) and total hospital length of stay (6 days). There were no differences in 30- and 90-day hospital readmissions, they noted.

“On additional age analysis, 65% of transplanted patients over 65 years are currently alive and were disease free at the end of the study period, compared to only 18% of their resected counterparts (P < .01),” they wrote.

Justifying transplant

The findings are notable because despite the effectiveness of transplant as an alternative treatment for unresectable HCC, older patients are often excluded from consideration for transplant. Most studies over the past 15 years have focused on patients aged under 60 years and the ability to extrapolate results to older patients has been limited. Further, results have been conflicting in older patients, the authors explained.

“This is particularly apposite at this time with prolonged life expectancy and the growing interest in improving cancer survivorship,” they noted, adding that “there is logic in challenging existing gold standards and traditional norms with real-life medical practice.

Indeed, the current findings suggest – perhaps contrary to common perceptions – that transplant in carefully selected patients “can be justified in older age groups and provide clinically meaningful and longer survival benefits,” they said, adding that “discussions should be guided by the potential for unfair age discriminations and precise terminology of physiologic rather than actual age.

“Such insights highlight the continued need for quality improvement in the surgical management of older patients, raising questions regarding current resource utilization among different age groups and how age can influence patterns of cancer care,” they concluded.

The authors reported having no disclosures.

sworcester@mdedge.com

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For select older patients, it is safe to switch to a lower dose of lenalidomide maintenance therapy and discontinue dexamethasone after 9 months. The regimen is safe and yields outcomes similar to those of standard, continuous lenalidomide/dexamethasone (Rd), according to new findings.

At a median follow-up of 37 months, event-free survival was 10.4 months in the experimental arm in which dexamethasone therapy was stopped (Rd-R) versus 6.9 months for standard therapy. The tailored approach also resulted in fewer adverse effects.

The authors noted that there was no difference in progression-free survival (PFS) and overall survival between the two groups.

“These results may be useful for the treatment of myeloma patients, since approximately one-third of patients not eligible for stem cell transplantation are intermediate fit, the population in our study,” said lead author Alessandra Larocca, MD, PhD, from the department of hematology-oncology of the University Hospital Città della Salute e della Scienza, Torino, Italy.

She said in an interview that they expect that these findings “may help to optimize the treatment of less-fit elderly patients by reducing the occurrence of adverse events and thus improving outcomes and preserving quality of life of these patients.”

This approach is a viable option for clinicians to consider for some patient subgroups. “This steroid-sparing approach can also be used in other combinations,” she said. “Ongoing trials are now evaluating steroid sparing in combination with monoclonal antibodies or the role of frailty-guided treatment.”

The study was published March 19, 2021, in Blood.
 

Curtailing steroids

Myeloma patients aged 75 years or older or who have comorbidities and functional impairments are an understudied population. They are more susceptible to adverse events that may negatively affect the duration of treatment and outcomes. Steroids are “scarcely tolerated” in the long term, even among younger patients, and “whether sparing dexamethasone is as effective as prolonged steroid exposure remains an open issue,” the authors wrote. There are still no clear data on the advantage of continuous steroid treatment as opposed to fixed-duration treatment for newly diagnosed patients.

In 2010, a study compared high-dose with low-dose dexamethasone. As expected, the rate of adverse events was lower among patients who received the low-dose steroid, but quite unexpectedly, deaths with high-dose dexamethasone were significantly higher than with low-dose dexamethasone.

The 1-year overall survival was 96% among patients who received the low dose of dexamethasone versus 87% with the standard high dose.

S. Vincent Rajkumar, MD, of the Mayo Clinic, Rochester, Minn., who was the lead author of the 2010 study, spoke with this new organization about the current study. “This is an important and practice-changing study,” he said. “We have already changed our practice and recommendations based on this study.”

He explained that, for transplant-ineligible patients, instead of initial therapy with bortezomib-lenalidomide-dexamethasone followed by Rd, they use lenalidomide alone without steroids.

“After 9 months of initial therapy, I now recommend we stop dexamethasone unless we are having problems controlling the myeloma, such as progressive disease,” Dr. Rajkumar said. “I congratulate the authors on a study that will improve the quality of life for our patients.”
 

Improved event-free survival

In this study, Dr. Larocca and colleagues investigated the efficacy and feasibility of a dose- and schedule-adjusted Rd regimen that was followed by maintenance Rd-R 10 mg/d and compared the regimen with continuous Rd in elderly, intermediate-fit patients who were newly diagnosed with multiple myeloma.

The primary endpoint was event-free survival, defined as progression/death from any cause, lenalidomide discontinuation, and any hematologic grade 4 or nonhematologic grade 3-4 adverse events.

The cohort consisted of 199 patients who were randomly assigned to receive either Rd-R (n = 101) or continuous Rd (n = 98). The median age was 75 years in the Rd-R arm and 76 years in the Rd arm; 52% of patients in the Rd-R group and 43% in the Rd group were classified as being intermediate fit not for age but for geriatric impairments.

With a median follow-up of 37 months, event-free survival was 10.4 months in the Rd-R arm versus 6.9 months in the Rd arm (hazard ratio, 0.70; P = .02). This benefit was maintained beyond nine cycles (median: 19.8 vs. 10.6 months for Rd-R vs. Rd; HR, 0.55; P = .03)

The median PFS was 20.2 months with Rd-R and 18.3 months with Rd (HR, 0.78; P = .16). The median overall survival was not reached. The 3-year overall survival was 74% with Rd-R and 63% with continuous Rd (HR, 0.62; P = .06). Among patients remaining on therapy after nine cycles, no difference in median PFS was observed between the two groups (24.3 vs. 18.7 months; HR, 0.73; P = .19).

Best response was similar for both groups, with an overall response rate of 78% versus 68% (P = .15). The very good partial response rate was 51% in the Rd-R arm versus 39% in the continuous Rd arm (P = .09).

Toxicities were similar between the two groups. Hematologic adverse events of at least grade 3 were reported in 26% of Rd-R patients versus 20% of Rd patients (P = .40). In both groups, the most frequent grade ≥3 hematologic toxicity was neutropenia (21% vs 18%). The most frequent grade ≥3 toxicities were nonhematologic. They occurred in 33% of Rd-R patients and 43% of Rd patients (P = .15). The most frequent nonhematologic toxicities were infections (10% vs. 12%), constitutional (3% vs. 12%), dermatologic (7% vs. 3%), and central nervous toxicities (2% vs. 6%).

The study was sponsored by Fondazione EMN Italy Onlus. Dr. Larocca has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and has served on the advisory boards for Bristol-Myers Squibb, Celgene, Janssen, and Takeda. Several coauthors also have disclosed relationships with industry. Dr. Rajkumar disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

Amid a substantial expansion of therapies in several drug classes for the treatment of osteoporosis, there has been a notable increase in the prescription of denosumab for patients with a cancer-related indication.

ogichobanov/iStock/Getty Images Plus

In an analysis of claims data from January 2009 to March 2020, the bisphosphonate alendronate represented more than 50% of all prescriptions for bone-directed therapies, but growth in the use of the monoclonal antibody denosumab overall and in cancer-related indications particularly was steady throughout the study period.

“In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, but use of both then declined,” Sara Cromer, MD, reported at the annual meeting of the Endocrine Society.

For malignancy-based prescriptions, denosumab surpassed either bisphosphonate by 2013 and then continued to rise.

Denosumab use “reached approximately 50% of all bone-directed medication use in the malignancy cohort” by the end of the study period, said Dr. Cromer, a clinical research fellow in endocrinology at Massachusetts General Hospital, Boston.

The claims data for this analysis was drawn from the Clinformatics Data Mart. The analysis was restricted to individuals aged older than 50 years who received a prescription for a bone-directed therapy. The 15.48 million prescriptions evaluated were drawn from 1.46 million unique individuals. The mean age was 69 years, and 89% of those prescribed a drug were women.
 

Oncologic indications one of two tracked cohorts

In the context of a large expansion of treatment options in several drug classes for osteoporosis, the objective of this claims analysis was to document trends in treatment choice, according to Dr. Cromer. She and her coinvestigators looked at prescriptions overall as well as in two cohorts defined by ICD codes. One included patients prescribed a prescription by an oncologist. The other included everyone else.

When all prescriptions for bone-directed therapy were evaluated over the study period, alendronate was the most commonly prescribed therapy, and its use increased over time. Prescriptions of zoledronic acid also rose, doubling over the study period, but use was very low in the beginning and it never climbed above 5%.

The proportion of prescriptions written for bisphosphonates other than alendronate and zoledronic acid “declined steadily” over the study period, Dr. Cromer reported.

Denosumab, a monoclonal antibody that targets a step in the process important to maturation of osteoclasts, was approved in 2010. It accounted for 10% of all prescriptions for osteoporosis by 2015 and 15% by 2018. It was still rising through the end of the study period.

In contrast, prescriptions of raloxifene, a selective estrogen receptor modulator, began to decline after 2013. In general, the rates of prescriptions for other agents, including some of the more recently approved drugs, such as teriparatide, abaloparatide, and romosozumab, changed very little over the study period. None of these therapies ever represented more than 2% of prescriptions.

When looking at the cohort of patients who received a bone-directed reason for a noncancer indication, the trends “paralleled those in the all-user analysis,” Dr. Cromer reported.
 

Denosumab use greater in privately insured

In the malignancy cohort, the decline in the use of bisphosphonates and the rise in the use of denosumab were most pronounced in patients who were privately insured. The increased use of denosumab over the study period “outpaced gains in use of other agents despite guidelines,” said Dr. Cromer, referring to the those issued by the Endocrine Society in 2019 .

In those guidelines, written for management of postmenopausal women at high risk of fractures, bisphosphonates are recommended for initial treatment while denosumab is recommended as an alternative. However, those guidelines do not provide specific recommendations for therapies directed at osteoporosis associated with cancer.

Guidelines for this population exist, including one published by the American Society of Clinical Oncology in 2019.

In the ASCO guidelines, oral bisphosphonates, intravenous bisphosphonates, and subcutaneous denosumab were all identified as “efficacious options,” according to Charles L. Shapiro, MD, director of breast cancer translational research, Mount Sinai Health System, New York.

Specifically, “all three of them work to reduce fractures and improve bone density in women with breast cancer in whom you are trying to prevent or treat osteoporosis,” Dr. Shapiro said in an interview.

There might be relative advantages for one therapy over another in specific subgroups defined by type of cancer or stage of cancer, but trials are not definitive for such outcomes as overall survival. Citing one comparative study associating denosumab with an 18% delay to first skeletal event in women with metastatic breast cancer, Dr. Shapiro observed, “I personally don’t consider an 18% delay [for this outcome] to be that clinically meaningful.”

Although major guidelines from ASCO have not so far favored denosumab over any bisphosphonate in routine care, Dr. Shapiro did not rule out the possibility that future studies will show differences.

Dr. Comer and Dr. Shapiro reported no relevant conflicts of interest.

Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.

Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.

“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).

Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
 

Ten-item score

To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.

The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).

Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.

Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).

Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).

“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
 

Higher scores, fewer assessments

The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).

Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).

Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).

Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).

Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).

Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.

Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).

mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).

On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).

High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
 

Volume counts

In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).

Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).

The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.

In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
 

Navigating treatment

“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”

Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.

Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.

“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”

The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.

Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.

Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.

“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).

Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
 

Ten-item score

To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.

The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).

Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.

Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).

Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).

“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
 

Higher scores, fewer assessments

The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).

Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).

Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).

Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).

Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).

Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.

Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).

mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).

On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).

High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
 

Volume counts

In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).

Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).

The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.

In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
 

Navigating treatment

“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”

Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.

Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.

“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”

The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.

Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.

Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.

“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).

Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
 

Ten-item score

To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.

The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).

Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.

Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).

Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).

“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
 

Higher scores, fewer assessments

The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).

Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).

Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).

Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).

Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).

Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.

Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).

mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).

On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).

High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
 

Volume counts

In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).

Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).

The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.

In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
 

Navigating treatment

“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”

Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.

Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.

“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”

The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

The first large study of its kind reveals that SARS-CoV-2 reinfections remain rare, although people older than 65 are at higher risk.

When researchers analyzed test results of 4 million people in Denmark, they found that less than 1% of those who tested positive experienced reinfection.

Initial infection was associated with about 80% protection overall against getting SARS-CoV-2 again. However, among those older than 65, the protection plummeted to 47%.

“Not everybody is protected against reinfection after a first infection. Older people are at higher risk of catching it again,” co–lead author Daniela Michlmayr, PhD, said in an interview. “Our findings emphasize the importance of policies to protect the elderly and of adhering to infection control measures and restrictions, even if previously infected with COVID-19.”
 

Verifying the need for vaccination

“The findings also highlight the need to vaccinate people who had COVID-19 before, as natural immunity to infection – especially among the elderly 65 and older – cannot be relied upon,” added Dr. Michlmayr, a researcher in the department of bacteria, parasites, and fungi at the Staten Serums Institut, Copenhagen.

The population-based observational study was published online March 17 in The Lancet.

“The findings make sense, as patients who are immunocompromised or of advanced age may not mount an immune response that is as long-lasting,” David Hirschwerk, MD, said in an interview. “It does underscore the importance of vaccination for people of more advanced age, even if they previously were infected with COVID.

“For those who were infected last spring and have not yet been vaccinated, this helps to support the value of still pursuing the vaccine,” added Dr. Hirschwerk, an infectious disease specialist at Northwell Health in Manhasset, N.Y.

Evidence on reinfection risk was limited prior to this study. “Little is known about protection against SARS-CoV-2 repeat infections, but two studies in the UK have found that immunity could last at least 5 to 6 months after infection,” the authors noted.

Along with co–lead author Christian Holm Hansen, PhD, Dr. Michlmayr and colleagues found that 2.11% of 525,339 individuals tested positive for SARS-CoV-2 during the first surge in Denmark from March to May 2020. Within this group, 0.65% tested positive during a second surge from September to December.

By the end of 2020, more than 10 million people had undergone free polymerase chain reaction testing by the Danish government or through the national TestDenmark program.

“My overall take is that it is great to have such a big dataset looking at this question,” E. John Wherry, PhD, said in an interview. The findings support “what we’ve seen in previous, smaller studies.”

Natural protection against reinfection of approximately 80% “is not as good as the vaccines, but not bad,” added Dr. Wherry, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia.
 

Age alters immunity?

“Our finding that older people were more likely than younger people to test positive again if they had already tested positive could be explained by natural age-related changes in the immune system of older adults, also referred to as immune senescence,” the authors noted.

The investigators found no significant differences in reinfection rates between women and men.

As with the previous research, this study also indicates that an initial bout with SARS-CoV-2 infection appears to confer protection for at least 6 months. The researchers found no significant differences between people who were followed for 3-6 months and those followed for 7 months or longer.
 

Variants not included

To account for possible bias among people who got tested repeatedly, Dr. Michlmayr and colleagues performed a sensitivity analysis in a subgroup. They assessed reinfection rates among people who underwent testing frequently and routinely – nurses, doctors, social workers, and health care assistants – and found that 1.2% tested positive a second time during the second surge.

A limitation of the study was the inability to correlate symptoms with risk for reinfection. Also, the researchers did not account for SARS-CoV-2 variants, noting that “during the study period, such variants were not yet established in Denmark; although into 2021 this pattern is changing.”

Asked to speculate whether the results would be different had the study accounted for variants, Dr. Hirschwerk said, “It depends upon the variant, but certainly for the B.1.351 variant, there already has been data clearly demonstrating risk of reinfection with SARS-CoV-2 despite prior infection with the original strain of virus.”

The emergence of SARS-CoV-2 variants of concern that could escape natural and vaccine-related immunity “complicates matters further,” Rosemary J. Boyton, MBBS, and Daniel M. Altmann, PhD, both of Imperial College London, wrote in an accompanying comment in The Lancet.

“Emerging variants of concern might shift immunity below a protective margin, prompting the need for updated vaccines. Interestingly, vaccine responses even after single dose are substantially enhanced in individuals with a history of infection with SARS-CoV-2,” they added.

The current study confirms that “the hope of protective immunity through natural infections might not be within our reach, and a global vaccination program with high efficacy vaccines is the enduring solution,” Dr. Boyton and Dr. Altmann noted.

Cause for alarm?

Despite evidence that reinfection is relatively rare, “many will find the data reported by Hansen and colleagues about protection through natural infection relatively alarming,” Dr. Boyton and Dr. Altmann wrote in their commentary. The 80% protection rate from reinfection in general and the 47% rate among people aged 65 and older “are more concerning figures than offered by previous studies.”

Vaccines appear to provide better quality, quantity, and durability of protection against repeated infection – measured in terms of neutralizing antibodies and T cells – compared with previous infection with SARS-CoV-2, Dr. Boyton and Dr. Altmann wrote.
 

More research needed

The duration of natural protection against reinfection remains an unanswered question, the researchers noted, “because too little time has elapsed since the beginning of the pandemic.”

Future prospective and longitudinal cohort studies coupled with molecular surveillance are needed to characterize antibody titers and waning of protection against repeat infections, the authors noted. Furthermore, more answers are needed regarding how some virus variants might contribute to reinfection risk.

No funding for the study has been reported. Dr. Michlmayr, Dr. Hirschwerk, Dr. Wherry, Dr. Boyton, and Dr. Altmann have disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results from a phase 2 placebo-controlled trial of the investigational antiamyloid drug donanemab show that the novel agent met the primary outcome of slowing cognitive decline in patients with early symptomatic Alzheimer’s disease (AD). 

Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.

As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.

The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.   

Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”

However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
 

Proof of concept?

The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.

The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.

The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.

Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.

The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.

This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
 

More research needed

Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.

Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:

• CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
• ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
• ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
• MMSE: 0.64 (95% CI, –0.4 to 1.67).

The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.

In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.

However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.

In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.

Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).

Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
 

Positive signal?

In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.

“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”

Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”

Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.

“I’m hopeful for the future,” Dr. Carrillo said.

Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.

“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.

He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.  

“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.

Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Practicing self-management techniques can help with lower urinary tract symptoms (LUTS) as much as taking medications, according to a new systematic review and meta-analysis.

Courtesy Dr. Camille Vaughan

The researchers reviewed the literature and analyzed eight randomized controlled trials enrolling a total of 1,006 men, who were experiencing lower urinary tract symptoms, according to the paper published in the Annals of Family Medicine. The self-management techniques practiced by patients as part of the trials included adjusting the timing of when patients drank fluids, reducing or eliminating caffeine and alcohol, adjusting the schedules of or replacing medications for other conditions, adjusting patients’ habits for urinating, and performing pelvic floor exercises for better performance of muscles controlling urination.

“Self-management interventions for lower urinary tract symptoms should be considered as a cheap and safe alternative to drug interventions with unfavorable safety profiles,” said study author Loai Albarqouni, MD, MSc, PhD, a post-doctoral fellow at Bond University in Australia.
 

Self-management yielded better results than usual care

Some of the symptoms experienced by participants in the trials included increased frequency of urination, urgency of urination, urination hesitancy, and dribbling. The researchers excluded research involving men with LUTS attributed to infections, those with prostate cancer, men who had undergone prostate surgery, and men with neurologic conditions.

Self-management techniques, which frequently included watchful waiting, significantly reduced symptom severity, compared with usual care in two of the trials, which included a total of 350 participants. Symptom severity was measured using the International Prostate Symptom Score (IPSS), with a mean difference of 7.44 points in favor of self-management (95% confidence interval, –8.82 to –6.06). A drop of 3 points on the IPSS scale is considered clinically meaningful.

The researchers found no difference in symptom severity at 6-12 weeks between self-management and drug therapy in their analysis of four trials that compared these approaches. Self-management resulted in better results in terms of waking at night because of the need to urinate, but there was no difference in the number of times urinating per day.

In two of the studies, investigators examined a combined self-management and drug therapy approach, compared with drug therapy by itself. In one of these studies, which included 133 participants, using the combination of treatments resulted in significantly lower symptom severity, compared with using drug therapy alone at 6 weeks, on the IPSS, with a mean difference of 2.30 (95% CI, –4.11 to –0.49).

One study involving men with involuntary loss of urine immediately after urination compared utilizing counseling, pelvic floor exercises, and urethral milking to work urine through the urethra. Pelvic floor exercise was the most effective at reducing urine loss.

Study author Dr. Albarqouni said better tools for physician education could help with implementing these strategies more effectively.
 

Analysis draws more attention to self-management approaches for men

Outside experts said that, while self-management approaches for these symptoms have long been recognized for women, this analysis draws more attention to the growing use of self-management approaches for men. They noted that hurdles, such as time constraints and physician education on proper technique, remain.

“Evidence suggests that the regular use of nondrug interventions is suboptimal for various reasons, including the inadequate reporting of the details of the interventions in the literature,” Dr. Albarqouni said.

Camille Vaughan, MD, MS, assistant professor of medicine at Emory University, where she has researched lower urinary tract symptoms, said advising patients on self-care is common in her practice, but should be more widely adopted in primary care.

Many patients don’t want to add to drugs that are often already a long list of medications, for fear of side effects and interactions, she said.

“If there are behavioral-based approaches that are appropriate, they’re often really interested in those strategies,” she said.

Barriers include the time it takes to teach patients these strategies and the confidence of the physicians themselves to instruct patients correctly, Dr. Vaughan said. Some physicians might be interested in the self-management approach for their patients, but “may not feel like they have all of the information at hand to share with patients,” she added.

“I think there are several decades of work showing the benefit of these types of strategies in women,” she said. “It’s relatively recent for men.” The analysis is a useful summary, she said.

“I think this should be really encouraging for providers and patients alike, because it’s highlighting the benefits of behavior and lifestyle-based strategies. A lot of these issues are going to impact men as they age,” she added.
 

High-quality data on self-management techniques have been limited

Scott Bauer, MD, MS, assistant professor of medicine at the University of California, San Francisco, and general internist at the San Francisco VA Medical Center, said he often prescribes self-management but has often had to review primary data from smaller trials and adapt that information to his own practice.

“I have felt like, for a long time, there’s been a lack of high-quality data and good synthesis of that data to really guide what I should specifically be recommending,” he said. “I’m very happy to see efforts to try to synthesize the data in a more comprehensive way and maybe work toward guidelines that can be applied more easily in clinical care.” It shows, he said, that “there is a decent amount of signal that should really be taken seriously both in a clinical context and for future research studies.”

Dr. Bauer noted that there is still a need to identify which patients are best suited for which approaches.

“We are very poor at diagnosing the specific etiology of LUTS – we don’t have great diagnostic tests or even phenotyping, and so that leaves clinicians with a very heterogeneous group of patients who all have the same syndrome of symptoms,” he explained. “But we don’t have much to guide us in terms of identifying who would benefit most from self-management overall, who would benefit from specific self-management techniques, and who would benefit from medication to target very specific mechanisms.”

Dr. Vaughan reported receiving funding from the Department of Veterans Affairs and National institutes of Health for research related to urinary symptom management, and that her spouse is an employee of Kimberly-Clark, which makes adult care products. Dr. Albarqouni and Dr. Bauer reported no relevant financial disclosures.

Practicing self-management techniques can help with lower urinary tract symptoms (LUTS) as much as taking medications, according to a new systematic review and meta-analysis.

Courtesy Dr. Camille Vaughan

The researchers reviewed the literature and analyzed eight randomized controlled trials enrolling a total of 1,006 men, who were experiencing lower urinary tract symptoms, according to the paper published in the Annals of Family Medicine. The self-management techniques practiced by patients as part of the trials included adjusting the timing of when patients drank fluids, reducing or eliminating caffeine and alcohol, adjusting the schedules of or replacing medications for other conditions, adjusting patients’ habits for urinating, and performing pelvic floor exercises for better performance of muscles controlling urination.

“Self-management interventions for lower urinary tract symptoms should be considered as a cheap and safe alternative to drug interventions with unfavorable safety profiles,” said study author Loai Albarqouni, MD, MSc, PhD, a post-doctoral fellow at Bond University in Australia.
 

Self-management yielded better results than usual care

Some of the symptoms experienced by participants in the trials included increased frequency of urination, urgency of urination, urination hesitancy, and dribbling. The researchers excluded research involving men with LUTS attributed to infections, those with prostate cancer, men who had undergone prostate surgery, and men with neurologic conditions.

Self-management techniques, which frequently included watchful waiting, significantly reduced symptom severity, compared with usual care in two of the trials, which included a total of 350 participants. Symptom severity was measured using the International Prostate Symptom Score (IPSS), with a mean difference of 7.44 points in favor of self-management (95% confidence interval, –8.82 to –6.06). A drop of 3 points on the IPSS scale is considered clinically meaningful.

The researchers found no difference in symptom severity at 6-12 weeks between self-management and drug therapy in their analysis of four trials that compared these approaches. Self-management resulted in better results in terms of waking at night because of the need to urinate, but there was no difference in the number of times urinating per day.

In two of the studies, investigators examined a combined self-management and drug therapy approach, compared with drug therapy by itself. In one of these studies, which included 133 participants, using the combination of treatments resulted in significantly lower symptom severity, compared with using drug therapy alone at 6 weeks, on the IPSS, with a mean difference of 2.30 (95% CI, –4.11 to –0.49).

One study involving men with involuntary loss of urine immediately after urination compared utilizing counseling, pelvic floor exercises, and urethral milking to work urine through the urethra. Pelvic floor exercise was the most effective at reducing urine loss.

Study author Dr. Albarqouni said better tools for physician education could help with implementing these strategies more effectively.
 

Analysis draws more attention to self-management approaches for men

Outside experts said that, while self-management approaches for these symptoms have long been recognized for women, this analysis draws more attention to the growing use of self-management approaches for men. They noted that hurdles, such as time constraints and physician education on proper technique, remain.

“Evidence suggests that the regular use of nondrug interventions is suboptimal for various reasons, including the inadequate reporting of the details of the interventions in the literature,” Dr. Albarqouni said.

Camille Vaughan, MD, MS, assistant professor of medicine at Emory University, where she has researched lower urinary tract symptoms, said advising patients on self-care is common in her practice, but should be more widely adopted in primary care.

Many patients don’t want to add to drugs that are often already a long list of medications, for fear of side effects and interactions, she said.

“If there are behavioral-based approaches that are appropriate, they’re often really interested in those strategies,” she said.

Barriers include the time it takes to teach patients these strategies and the confidence of the physicians themselves to instruct patients correctly, Dr. Vaughan said. Some physicians might be interested in the self-management approach for their patients, but “may not feel like they have all of the information at hand to share with patients,” she added.

“I think there are several decades of work showing the benefit of these types of strategies in women,” she said. “It’s relatively recent for men.” The analysis is a useful summary, she said.

“I think this should be really encouraging for providers and patients alike, because it’s highlighting the benefits of behavior and lifestyle-based strategies. A lot of these issues are going to impact men as they age,” she added.
 

High-quality data on self-management techniques have been limited

Scott Bauer, MD, MS, assistant professor of medicine at the University of California, San Francisco, and general internist at the San Francisco VA Medical Center, said he often prescribes self-management but has often had to review primary data from smaller trials and adapt that information to his own practice.

“I have felt like, for a long time, there’s been a lack of high-quality data and good synthesis of that data to really guide what I should specifically be recommending,” he said. “I’m very happy to see efforts to try to synthesize the data in a more comprehensive way and maybe work toward guidelines that can be applied more easily in clinical care.” It shows, he said, that “there is a decent amount of signal that should really be taken seriously both in a clinical context and for future research studies.”

Dr. Bauer noted that there is still a need to identify which patients are best suited for which approaches.

“We are very poor at diagnosing the specific etiology of LUTS – we don’t have great diagnostic tests or even phenotyping, and so that leaves clinicians with a very heterogeneous group of patients who all have the same syndrome of symptoms,” he explained. “But we don’t have much to guide us in terms of identifying who would benefit most from self-management overall, who would benefit from specific self-management techniques, and who would benefit from medication to target very specific mechanisms.”

Dr. Vaughan reported receiving funding from the Department of Veterans Affairs and National institutes of Health for research related to urinary symptom management, and that her spouse is an employee of Kimberly-Clark, which makes adult care products. Dr. Albarqouni and Dr. Bauer reported no relevant financial disclosures.

Practicing self-management techniques can help with lower urinary tract symptoms (LUTS) as much as taking medications, according to a new systematic review and meta-analysis.

Courtesy Dr. Camille Vaughan

The researchers reviewed the literature and analyzed eight randomized controlled trials enrolling a total of 1,006 men, who were experiencing lower urinary tract symptoms, according to the paper published in the Annals of Family Medicine. The self-management techniques practiced by patients as part of the trials included adjusting the timing of when patients drank fluids, reducing or eliminating caffeine and alcohol, adjusting the schedules of or replacing medications for other conditions, adjusting patients’ habits for urinating, and performing pelvic floor exercises for better performance of muscles controlling urination.

“Self-management interventions for lower urinary tract symptoms should be considered as a cheap and safe alternative to drug interventions with unfavorable safety profiles,” said study author Loai Albarqouni, MD, MSc, PhD, a post-doctoral fellow at Bond University in Australia.
 

Self-management yielded better results than usual care

Some of the symptoms experienced by participants in the trials included increased frequency of urination, urgency of urination, urination hesitancy, and dribbling. The researchers excluded research involving men with LUTS attributed to infections, those with prostate cancer, men who had undergone prostate surgery, and men with neurologic conditions.

Self-management techniques, which frequently included watchful waiting, significantly reduced symptom severity, compared with usual care in two of the trials, which included a total of 350 participants. Symptom severity was measured using the International Prostate Symptom Score (IPSS), with a mean difference of 7.44 points in favor of self-management (95% confidence interval, –8.82 to –6.06). A drop of 3 points on the IPSS scale is considered clinically meaningful.

The researchers found no difference in symptom severity at 6-12 weeks between self-management and drug therapy in their analysis of four trials that compared these approaches. Self-management resulted in better results in terms of waking at night because of the need to urinate, but there was no difference in the number of times urinating per day.

In two of the studies, investigators examined a combined self-management and drug therapy approach, compared with drug therapy by itself. In one of these studies, which included 133 participants, using the combination of treatments resulted in significantly lower symptom severity, compared with using drug therapy alone at 6 weeks, on the IPSS, with a mean difference of 2.30 (95% CI, –4.11 to –0.49).

One study involving men with involuntary loss of urine immediately after urination compared utilizing counseling, pelvic floor exercises, and urethral milking to work urine through the urethra. Pelvic floor exercise was the most effective at reducing urine loss.

Study author Dr. Albarqouni said better tools for physician education could help with implementing these strategies more effectively.
 

Analysis draws more attention to self-management approaches for men

Outside experts said that, while self-management approaches for these symptoms have long been recognized for women, this analysis draws more attention to the growing use of self-management approaches for men. They noted that hurdles, such as time constraints and physician education on proper technique, remain.

“Evidence suggests that the regular use of nondrug interventions is suboptimal for various reasons, including the inadequate reporting of the details of the interventions in the literature,” Dr. Albarqouni said.

Camille Vaughan, MD, MS, assistant professor of medicine at Emory University, where she has researched lower urinary tract symptoms, said advising patients on self-care is common in her practice, but should be more widely adopted in primary care.

Many patients don’t want to add to drugs that are often already a long list of medications, for fear of side effects and interactions, she said.

“If there are behavioral-based approaches that are appropriate, they’re often really interested in those strategies,” she said.

Barriers include the time it takes to teach patients these strategies and the confidence of the physicians themselves to instruct patients correctly, Dr. Vaughan said. Some physicians might be interested in the self-management approach for their patients, but “may not feel like they have all of the information at hand to share with patients,” she added.

“I think there are several decades of work showing the benefit of these types of strategies in women,” she said. “It’s relatively recent for men.” The analysis is a useful summary, she said.

“I think this should be really encouraging for providers and patients alike, because it’s highlighting the benefits of behavior and lifestyle-based strategies. A lot of these issues are going to impact men as they age,” she added.
 

High-quality data on self-management techniques have been limited

Scott Bauer, MD, MS, assistant professor of medicine at the University of California, San Francisco, and general internist at the San Francisco VA Medical Center, said he often prescribes self-management but has often had to review primary data from smaller trials and adapt that information to his own practice.

“I have felt like, for a long time, there’s been a lack of high-quality data and good synthesis of that data to really guide what I should specifically be recommending,” he said. “I’m very happy to see efforts to try to synthesize the data in a more comprehensive way and maybe work toward guidelines that can be applied more easily in clinical care.” It shows, he said, that “there is a decent amount of signal that should really be taken seriously both in a clinical context and for future research studies.”

Dr. Bauer noted that there is still a need to identify which patients are best suited for which approaches.

“We are very poor at diagnosing the specific etiology of LUTS – we don’t have great diagnostic tests or even phenotyping, and so that leaves clinicians with a very heterogeneous group of patients who all have the same syndrome of symptoms,” he explained. “But we don’t have much to guide us in terms of identifying who would benefit most from self-management overall, who would benefit from specific self-management techniques, and who would benefit from medication to target very specific mechanisms.”

Dr. Vaughan reported receiving funding from the Department of Veterans Affairs and National institutes of Health for research related to urinary symptom management, and that her spouse is an employee of Kimberly-Clark, which makes adult care products. Dr. Albarqouni and Dr. Bauer reported no relevant financial disclosures.

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

copyright DesignPics/Thinkstock

No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

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No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

copyright DesignPics/Thinkstock

No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.

Palliative care for people with dementia is increasingly recognized as a way to improve quality of life and provide relief from the myriad physical and psychological symptoms of advancing neurodegenerative disease. But unlike in cancer, relatively few patients with terminal dementia receive referrals to palliative care.

A new literature review has found these referrals to be all over the map among patients with dementia – with many occurring very late in the disease process – and do not reflect any consistent criteria based on patient needs.

For their research, published March 2 in the Journal of the American Geriatrics Society, Li Mo, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues looked at nearly 60 studies dating back to the early 1990s that contained information on referrals to palliative care for patients with dementia. While a palliative care approach can be provided by nonspecialists, all the included studies dealt at least in part with specialist care.
 

Standardized criteria is lacking

The investigators found advanced or late-stage dementia to be the most common reason cited for referral, with three quarters of the studies recommending palliative care for late-stage or advanced dementia, generally without qualifying what symptoms or needs were present. Patients received palliative care across a range of settings, including nursing homes, hospitals, and their own homes, though many articles did not include information on where patients received care.

A fifth of the articles suggested that medical complications of dementia including falls, pneumonia, and ulcers should trigger referrals to palliative care, while another fifth cited poor prognosis, defined varyingly as having between 2 years and 6 months likely left to live. Poor nutrition status was identified in 10% of studies as meriting referral.

Only 20% of the studies identified patient needs – evidence of psychological distress or functional decline, for example – as criteria for referral, despite these being ubiquitous in dementia. The authors said they were surprised by this finding, which could possibly be explained, they wrote, by “the interest among geriatrician, neurologist, and primary care teams to provide good symptom management,” reflecting a de facto palliative care approach. “There is also significant stigma associated with a specialist palliative care referral,” the authors noted.

Curiously, the researchers noted, a new diagnosis of dementia in more than a quarter of the studies triggered referral, a finding that possibly reflected delayed diagnoses.

The findings revealed “heterogeneity in the literature in reasons for involving specialist palliative care, which may partly explain the variation in patterns of palliative care referral,” Dr. Mo and colleagues wrote, stressing that more standardized criteria are urgently needed to bring dementia in line with cancer in terms of providing timely palliative care.

Patients with advancing dementia have little chance to self-report symptoms, meaning that more attention to patient complaints earlier in the disease course, and greater sensitivity to patient distress, are required. By routinely screening symptoms, clinicians could use specific cutoffs “as triggers to initiate automatic timely palliative care referral,” the authors concluded, noting that more research was needed before these cutoffs, whether based on symptom intensity or other measures, could be calculated.

Dr. Mo and colleagues acknowledged as weaknesses of their study the fact that a third of the articles in the review were based on expert consensus, while others did not distinguish clearly between primary and specialist palliative care.
 

A starting point for further discussion

Asked to comment on the findings, Elizabeth Sampson, MD, a palliative care researcher at University College London, praised Dr. Mo and colleagues’ study as “starting to pull together the strands” of a systematic approach to referrals and access to palliative care in dementia.

Dr. Sampson’s group is leading a UK-government funded research effort that aims to develop cost-effective palliative care interventions in dementia, in part through a tool that uses caregiver reports to assess symptom burden and patient needs. The research program “is founded on a needs-based approach, which aims to look at people’s individual needs and responding to them in a proactive way,” she said.

One of the obstacles to timely palliative care in dementia, Dr. Sampson said, is weighing resource allocation against what can be wildly varying prognoses. “Hospices understand when someone has terminal cancer and [is] likely to die within a few weeks, but it’s not unheard of for someone in very advanced stages of dementia to live another year,” she said. “There are concerns that a rapid increase in people with dementia being moved to palliative care could overwhelm already limited hospice capacity. We would argue that the best approach is to get palliative care out to where people with dementia live, which is usually the care home.”

Dr. Mo and colleagues’ study received funding from the National Institutes of Health, and its authors disclosed no financial conflicts of interest. Dr. Sampson’s work is supported by the UK’s Economic and Social Research Council and National Institute for Health Research. She disclosed no conflicts of interest.