Rheumatology News

Low-dose aspirin taken daily fails to reduce the risk of fractures and increases the risk of serious falls in older adults, a new study finds.

Previous research suggests that aspirin may reduce the risk of fragility fractures by delaying bone loss, but the direct effects of aspirin on bone microarchitecture and the association between aspirin use and fracture risk in humans has not been explored, corresponding author Anna L. Barker, PhD, and colleagues wrote in their paper published in JAMA Internal Medicine.

Dr. Barker, who is executive director of research and innovation for Silverchain (a senior care program), said, in an interview, that she and her coauthors hypothesized “that aspirin could reduce both falls and fractures by reducing cardiovascular-associated physical and cognitive impairments and the anti-inflammatory properties mediating bone remodeling.”
 

Study methods and results

In the ASPREE-FRACTURE substudy, the authors examined the impact of daily low-dose aspirin (100 mg) on incidence of any fracture in more than 16,000 community-dwelling adults aged 70 years and older. A secondary endpoint was the incidence of serious falls, defined as falls requiring a hospital visit. Individuals with chronic illness and cardiovascular or cerebrovascular disease were excluded, as were those with dementia or other cognitive impairment, or a physical disability.

The study population included 16,703 participants enrolled in the larger Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial between 2010 and 2014. Of these, 8,322 were randomized to aspirin and 8,381 to a placebo. The median age was 74 years, and 55% of the participants were women.

Over a median follow-up of 4.6 years (76,219 total person-years), the risk of first fracture was similar between the aspirin and placebo groups (hazard ratio, 0.97), but the risk of serious falls was significantly higher in the aspirin group (884 falls vs. 804 falls, P = .01).

The incidence of first fracture was similar between the aspirin and placebo groups (813 vs. 718), as was the incidence of all fractures (1,394 and 1,471, respectively).

The results for both fractures and falls were essentially unchanged in a multivariate analysis controlling for variables known to affect fracture and fall risk and remained similar for different types of fractures (hip, trauma-related, nonpathological) as well, the researchers noted.

In their discussion, the researchers wrote that the clinical significance of the study is the inability of aspirin to reduce the risk of fractures in otherwise healthy older adults. They expressed surprise at the increase in serious falls, citing their hypothesis that the antiplatelet effects of aspirin may reduce cardiovascular and cerebrovascular events, thereby slowing physical decline and decreasing fall risk.

The increased risk of serious falls was not accompanied by an increase in fractures, and the increased fall risk was similar across subgroups of aspirin users, the researchers said.

Low-dose aspirin’s failure to reduce the risk of fractures but increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.

The study findings were limited by several factors including the relatively homogeneous older and healthy population, and possible insufficient study duration to allow for changes in fracture and fall risk, the researchers noted. Other potential limitations include that the dose of aspirin used in the study was too low to affect bone remodeling and the lack of data on bone density, rheumatoid arthritis, and osteoporosis, they said.

However, the results were strengthened by the large sample size and high participant retention rate, and represent the first known examination of data from a randomized, controlled trial of the effect of aspirin on fractures, they added.
 

Setting the stage for more research

Overall, “This study adds to the growing body of evidence from other studies that the use of aspirin in people who do not have a risk of cardiovascular disease or stroke provides little benefit,” said Dr. Barker, who is also a professor at Monash University, Melbourne, Australia. However, “Older adults with a medical reason to take aspirin should continue to do so,” she emphasized.

“The most important thing the study showed is the primary endpoint, which was that aspirin use does not have an effect on fracture risk,” said Neil Skolnik, MD, of Sidney Kimmel Medical College, Philadelphia, in an interview.

“The increase in serious falls, as defined by a fall resulting in a visit to a hospital, is likely due to an increased risk of bleeding after a fall on aspirin,” said Dr. Skolnik, who was not involved in the study. Dr. Skolnik added that the current study findings support the current recommendations of the United States Preventive Services Task Force, which he quoted as follows, “The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.”

The study was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health; the National Health and Medical Research Council (Australia); Monash University; and the Victorian Cancer Agency. Lead author Dr. Barker was supported in part by the NHMRC and also disclosed grants from the NHMRC outside the current study. The ASPREE substudy also was supported by the University of Pittsburgh Claude D. Pepper Older American Independence Center and the Wake Forest University Claude D. Pepper Older Americans Independence Center. Bayer AG provided the aspirin used in the study but had no other role. Dr. Skolnik had no financial conflicts to disclose, but he serves on the editorial advisory board of Family Practice News.

Low-dose aspirin taken daily fails to reduce the risk of fractures and increases the risk of serious falls in older adults, a new study finds.

Previous research suggests that aspirin may reduce the risk of fragility fractures by delaying bone loss, but the direct effects of aspirin on bone microarchitecture and the association between aspirin use and fracture risk in humans has not been explored, corresponding author Anna L. Barker, PhD, and colleagues wrote in their paper published in JAMA Internal Medicine.

Dr. Barker, who is executive director of research and innovation for Silverchain (a senior care program), said, in an interview, that she and her coauthors hypothesized “that aspirin could reduce both falls and fractures by reducing cardiovascular-associated physical and cognitive impairments and the anti-inflammatory properties mediating bone remodeling.”
 

Study methods and results

In the ASPREE-FRACTURE substudy, the authors examined the impact of daily low-dose aspirin (100 mg) on incidence of any fracture in more than 16,000 community-dwelling adults aged 70 years and older. A secondary endpoint was the incidence of serious falls, defined as falls requiring a hospital visit. Individuals with chronic illness and cardiovascular or cerebrovascular disease were excluded, as were those with dementia or other cognitive impairment, or a physical disability.

The study population included 16,703 participants enrolled in the larger Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial between 2010 and 2014. Of these, 8,322 were randomized to aspirin and 8,381 to a placebo. The median age was 74 years, and 55% of the participants were women.

Over a median follow-up of 4.6 years (76,219 total person-years), the risk of first fracture was similar between the aspirin and placebo groups (hazard ratio, 0.97), but the risk of serious falls was significantly higher in the aspirin group (884 falls vs. 804 falls, P = .01).

The incidence of first fracture was similar between the aspirin and placebo groups (813 vs. 718), as was the incidence of all fractures (1,394 and 1,471, respectively).

The results for both fractures and falls were essentially unchanged in a multivariate analysis controlling for variables known to affect fracture and fall risk and remained similar for different types of fractures (hip, trauma-related, nonpathological) as well, the researchers noted.

In their discussion, the researchers wrote that the clinical significance of the study is the inability of aspirin to reduce the risk of fractures in otherwise healthy older adults. They expressed surprise at the increase in serious falls, citing their hypothesis that the antiplatelet effects of aspirin may reduce cardiovascular and cerebrovascular events, thereby slowing physical decline and decreasing fall risk.

The increased risk of serious falls was not accompanied by an increase in fractures, and the increased fall risk was similar across subgroups of aspirin users, the researchers said.

Low-dose aspirin’s failure to reduce the risk of fractures but increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.

The study findings were limited by several factors including the relatively homogeneous older and healthy population, and possible insufficient study duration to allow for changes in fracture and fall risk, the researchers noted. Other potential limitations include that the dose of aspirin used in the study was too low to affect bone remodeling and the lack of data on bone density, rheumatoid arthritis, and osteoporosis, they said.

However, the results were strengthened by the large sample size and high participant retention rate, and represent the first known examination of data from a randomized, controlled trial of the effect of aspirin on fractures, they added.
 

Setting the stage for more research

Overall, “This study adds to the growing body of evidence from other studies that the use of aspirin in people who do not have a risk of cardiovascular disease or stroke provides little benefit,” said Dr. Barker, who is also a professor at Monash University, Melbourne, Australia. However, “Older adults with a medical reason to take aspirin should continue to do so,” she emphasized.

“The most important thing the study showed is the primary endpoint, which was that aspirin use does not have an effect on fracture risk,” said Neil Skolnik, MD, of Sidney Kimmel Medical College, Philadelphia, in an interview.

“The increase in serious falls, as defined by a fall resulting in a visit to a hospital, is likely due to an increased risk of bleeding after a fall on aspirin,” said Dr. Skolnik, who was not involved in the study. Dr. Skolnik added that the current study findings support the current recommendations of the United States Preventive Services Task Force, which he quoted as follows, “The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.”

The study was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health; the National Health and Medical Research Council (Australia); Monash University; and the Victorian Cancer Agency. Lead author Dr. Barker was supported in part by the NHMRC and also disclosed grants from the NHMRC outside the current study. The ASPREE substudy also was supported by the University of Pittsburgh Claude D. Pepper Older American Independence Center and the Wake Forest University Claude D. Pepper Older Americans Independence Center. Bayer AG provided the aspirin used in the study but had no other role. Dr. Skolnik had no financial conflicts to disclose, but he serves on the editorial advisory board of Family Practice News.

Low-dose aspirin taken daily fails to reduce the risk of fractures and increases the risk of serious falls in older adults, a new study finds.

Previous research suggests that aspirin may reduce the risk of fragility fractures by delaying bone loss, but the direct effects of aspirin on bone microarchitecture and the association between aspirin use and fracture risk in humans has not been explored, corresponding author Anna L. Barker, PhD, and colleagues wrote in their paper published in JAMA Internal Medicine.

Dr. Barker, who is executive director of research and innovation for Silverchain (a senior care program), said, in an interview, that she and her coauthors hypothesized “that aspirin could reduce both falls and fractures by reducing cardiovascular-associated physical and cognitive impairments and the anti-inflammatory properties mediating bone remodeling.”
 

Study methods and results

In the ASPREE-FRACTURE substudy, the authors examined the impact of daily low-dose aspirin (100 mg) on incidence of any fracture in more than 16,000 community-dwelling adults aged 70 years and older. A secondary endpoint was the incidence of serious falls, defined as falls requiring a hospital visit. Individuals with chronic illness and cardiovascular or cerebrovascular disease were excluded, as were those with dementia or other cognitive impairment, or a physical disability.

The study population included 16,703 participants enrolled in the larger Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial between 2010 and 2014. Of these, 8,322 were randomized to aspirin and 8,381 to a placebo. The median age was 74 years, and 55% of the participants were women.

Over a median follow-up of 4.6 years (76,219 total person-years), the risk of first fracture was similar between the aspirin and placebo groups (hazard ratio, 0.97), but the risk of serious falls was significantly higher in the aspirin group (884 falls vs. 804 falls, P = .01).

The incidence of first fracture was similar between the aspirin and placebo groups (813 vs. 718), as was the incidence of all fractures (1,394 and 1,471, respectively).

The results for both fractures and falls were essentially unchanged in a multivariate analysis controlling for variables known to affect fracture and fall risk and remained similar for different types of fractures (hip, trauma-related, nonpathological) as well, the researchers noted.

In their discussion, the researchers wrote that the clinical significance of the study is the inability of aspirin to reduce the risk of fractures in otherwise healthy older adults. They expressed surprise at the increase in serious falls, citing their hypothesis that the antiplatelet effects of aspirin may reduce cardiovascular and cerebrovascular events, thereby slowing physical decline and decreasing fall risk.

The increased risk of serious falls was not accompanied by an increase in fractures, and the increased fall risk was similar across subgroups of aspirin users, the researchers said.

Low-dose aspirin’s failure to reduce the risk of fractures but increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.

The study findings were limited by several factors including the relatively homogeneous older and healthy population, and possible insufficient study duration to allow for changes in fracture and fall risk, the researchers noted. Other potential limitations include that the dose of aspirin used in the study was too low to affect bone remodeling and the lack of data on bone density, rheumatoid arthritis, and osteoporosis, they said.

However, the results were strengthened by the large sample size and high participant retention rate, and represent the first known examination of data from a randomized, controlled trial of the effect of aspirin on fractures, they added.
 

Setting the stage for more research

Overall, “This study adds to the growing body of evidence from other studies that the use of aspirin in people who do not have a risk of cardiovascular disease or stroke provides little benefit,” said Dr. Barker, who is also a professor at Monash University, Melbourne, Australia. However, “Older adults with a medical reason to take aspirin should continue to do so,” she emphasized.

“The most important thing the study showed is the primary endpoint, which was that aspirin use does not have an effect on fracture risk,” said Neil Skolnik, MD, of Sidney Kimmel Medical College, Philadelphia, in an interview.

“The increase in serious falls, as defined by a fall resulting in a visit to a hospital, is likely due to an increased risk of bleeding after a fall on aspirin,” said Dr. Skolnik, who was not involved in the study. Dr. Skolnik added that the current study findings support the current recommendations of the United States Preventive Services Task Force, which he quoted as follows, “The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.”

The study was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health; the National Health and Medical Research Council (Australia); Monash University; and the Victorian Cancer Agency. Lead author Dr. Barker was supported in part by the NHMRC and also disclosed grants from the NHMRC outside the current study. The ASPREE substudy also was supported by the University of Pittsburgh Claude D. Pepper Older American Independence Center and the Wake Forest University Claude D. Pepper Older Americans Independence Center. Bayer AG provided the aspirin used in the study but had no other role. Dr. Skolnik had no financial conflicts to disclose, but he serves on the editorial advisory board of Family Practice News.

The incidence of dementia in patients with rheumatoid arthritis who took either a biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) was significantly lower than the rate observed in patients who take only a conventional synthetic DMARD (csDMARD) in a national database study.

The work builds on previous research indicating a higher risk of Alzheimer’s disease and related dementias in people with RA. While joint pain and swelling are the cardinal symptoms of RA, its systemic inflammation leads to multiple systemic manifestations, offering biologically plausible links with cognitive decline. In addition, patients with RA have high prevalence of cardiovascular disease, diabetes, depression, disability, and physical inactivity, all of which are risk factors for dementia.

Chronic neuroinflammation secondary to either intrinsic or systemic stimuli is thought to play a key role in dementia development, especially Alzheimer’s dementia (AD). Research showing a role of tumor necrosis factor–alpha (TNF-alpha) in the development of dementia has piqued interest in a potential protective effect of TNF inhibitors. “TNF-alpha is thought to have an important role in different stages of the pathophysiology and disease progression of Alzheimer’s disease,” study first author Sebastian E. Sattui, MD, assistant professor of medicine at the University of Pittsburgh and director of the University of Pittsburgh Vasculitis Center, said in an interview. “Animal models have shown that TNF inhibition reduces microgliosis, neuronal loss, and tau phosphorylation. Cognitive improvement has been seen in two trials with Alzheimer’s disease patients, but were not in rheumatoid arthritis patients.”

In the newest study, published online in Seminars in Arthritis and Rheumatism, Dr. Sattui and colleagues suggest that a lower risk for dementia seen with bDMARDs and tsDMARDs may be attributable to an overall greater decrease in inflammation rather than any mechanism of action specific to these drugs.

In the study of Centers for Medicare & Medicaid Services claims during 2006-2017 for 141,326 adult patients with RA, the crude incident rates were 2.0 per 100 person-years (95% confidence interval, 1.9-2.1) for patients on csDMARDs and 1.3 (95% CI, 1.2-1.4) for patients on any b/tsDMARD. There were 3,794 cases of incident dementia during follow-up among 233,271 initiations of any DMARD. The adjusted risk for dementia among users of bDMARDs or tsDMARDs was 19% lower than the adjusted risk for patients on csDMARDs (hazard ratio, 0.81; 95% CI, 0.76-0.87). No significant differences were found between classes of bDMARDs or tsDMARDs.

Dr. Sattui and coauthors’ investigation included adults aged at least 40 years with two RA diagnoses by a rheumatologist more than 7 and less than 365 days apart. Those with prior dementia diagnoses were excluded. Their analysis found the risk of incident dementia to be comparable between patients receiving TNF inhibitors (HR, 0.86; 95% CI, 0.80-0.93), non-TNFi bDMARDs (HR, 0.76; 95% CI, 0.70-0.83), and tsDMARDs (HR, 0.69; 95% CI, 0.53-0.90), with csDMARDs as the referent. A second subgroup analysis looking at patients with prior methotrexate use who were taking bDMARDs or tsDMARDs revealed similar decreases in risk of incident dementia, compared with patients taking bDMARDs or tsDMARDs along with methotrexate at baseline.

“NSAIDs and glucocorticoids have been studied in RCTs [randomized, controlled trials],” Dr. Sattui said in the interview. “Despite initial observational data that showed some signal for improvement, no benefit was observed in either of the RCTs. Other agents with possible anti-inflammatory effects and more benign profiles, such as curcumin, are being studied. There are also ongoing trials looking into the use of JAK [Janus kinase] inhibitors or [interleukin]-1 inhibition in dementia.”

He added: “There is a need to better study the association between cognition and disease activity, as well as treat-to-target strategies, prospectively in patients with RA. It is important to also acknowledge that any of these findings might be just specific for RA, so extrapolation to non-RA individuals might be limited.”

In commenting on the findings of the study, Rishi J. Desai, PhD, assistant professor of medicine in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston, said that “superior inflammation control with biologics or targeted DMARDs is an interesting hypothesis explaining the observed findings. It merits further investigation and replication in diverse populations.” He added: “It should be noted that a key challenge in evaluating this hypothesis using insurance claims data is unavailability of some important factors such as socioeconomic status and patient frailty. These may be driving treatment selection between conventional DMARDs, which are cheaper with more benign adverse-event profiles, and biologic or targeted DMARDs, which are more expensive with a less favorable adverse-event profile.”
 

Prior research

Several studies have investigated the effect of DMARDs, including bDMARDs like tumor necrosis factor inhibitors, on incident dementia in patients with RA.

Among this research is a study by Dr. Desai and colleagues that looked at comparative risk of AD and related dementia in 22,569 Medicare beneficiaries receiving tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors in comparison with abatacept (a T-cell activation inhibitor). No differentiating risk associations were found in this cohort study.

Other past studies include:

• A study comparing about 21,000 patients with RA and a non-RA cohort of about 62,000 found a 37% reduction in dementia development among RA patients receiving DMARDs. The effect was dose dependent, greater with high cumulative dosages, and was found in both men and women and in subgroups younger and older than 65 years.
• A retrospective study of electronic health records from 56 million adult patients identified a subset of patients with RA, psoriasis, ankylosing spondylitis, ulcerative colitis, or Crohn’s disease in whom systemic inflammation increased risk for AD through a mechanism involving TNF. The risk for AD in patients was lowered by treatment with etanercept, adalimumab, infliximab, or methotrexate, with larger reductions observed in younger patients than in older patients receiving TNF blockers.
• A propensity score–matched retrospective cohort study in 2,510 U.S. veterans with RA found that use of a TNF inhibitor reduced the risk of dementia by 36%, compared with control patients (HR, 0.64; 95% CI, 0.52-0.80), and the effect was consistent over 5-20 years post RA diagnosis.
• In a retrospective, multinational, matched, case-control study of patients older than 50 years with RA, prior methotrexate use was associated with lower dementia risk (OR, 0.71; 95% CI, 0.52-0.98). Use of methotrexate longer than 4 years demonstrated the lowest dementia risk (odds ratio, 0.37; 95% CI, 0.17-0.79).

These past studies, Dr. Sattui and colleagues pointed out, have multiple shortcomings, including case-control design, different definitions of exposure or outcomes, and inadequate control of confounders, underscoring the need for more rigorous studies.

Several authors of the CMS claims study disclosed research support, grants, and consulting fees from pharmaceutical companies. The research was supported by a grant from the National Institutes of Health. Dr. Desai disclosed that he has received funding from the National Institute on Aging for drug repurposing studies of dementia.

The incidence of dementia in patients with rheumatoid arthritis who took either a biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) was significantly lower than the rate observed in patients who take only a conventional synthetic DMARD (csDMARD) in a national database study.

The work builds on previous research indicating a higher risk of Alzheimer’s disease and related dementias in people with RA. While joint pain and swelling are the cardinal symptoms of RA, its systemic inflammation leads to multiple systemic manifestations, offering biologically plausible links with cognitive decline. In addition, patients with RA have high prevalence of cardiovascular disease, diabetes, depression, disability, and physical inactivity, all of which are risk factors for dementia.

Chronic neuroinflammation secondary to either intrinsic or systemic stimuli is thought to play a key role in dementia development, especially Alzheimer’s dementia (AD). Research showing a role of tumor necrosis factor–alpha (TNF-alpha) in the development of dementia has piqued interest in a potential protective effect of TNF inhibitors. “TNF-alpha is thought to have an important role in different stages of the pathophysiology and disease progression of Alzheimer’s disease,” study first author Sebastian E. Sattui, MD, assistant professor of medicine at the University of Pittsburgh and director of the University of Pittsburgh Vasculitis Center, said in an interview. “Animal models have shown that TNF inhibition reduces microgliosis, neuronal loss, and tau phosphorylation. Cognitive improvement has been seen in two trials with Alzheimer’s disease patients, but were not in rheumatoid arthritis patients.”

In the newest study, published online in Seminars in Arthritis and Rheumatism, Dr. Sattui and colleagues suggest that a lower risk for dementia seen with bDMARDs and tsDMARDs may be attributable to an overall greater decrease in inflammation rather than any mechanism of action specific to these drugs.

In the study of Centers for Medicare & Medicaid Services claims during 2006-2017 for 141,326 adult patients with RA, the crude incident rates were 2.0 per 100 person-years (95% confidence interval, 1.9-2.1) for patients on csDMARDs and 1.3 (95% CI, 1.2-1.4) for patients on any b/tsDMARD. There were 3,794 cases of incident dementia during follow-up among 233,271 initiations of any DMARD. The adjusted risk for dementia among users of bDMARDs or tsDMARDs was 19% lower than the adjusted risk for patients on csDMARDs (hazard ratio, 0.81; 95% CI, 0.76-0.87). No significant differences were found between classes of bDMARDs or tsDMARDs.

Dr. Sattui and coauthors’ investigation included adults aged at least 40 years with two RA diagnoses by a rheumatologist more than 7 and less than 365 days apart. Those with prior dementia diagnoses were excluded. Their analysis found the risk of incident dementia to be comparable between patients receiving TNF inhibitors (HR, 0.86; 95% CI, 0.80-0.93), non-TNFi bDMARDs (HR, 0.76; 95% CI, 0.70-0.83), and tsDMARDs (HR, 0.69; 95% CI, 0.53-0.90), with csDMARDs as the referent. A second subgroup analysis looking at patients with prior methotrexate use who were taking bDMARDs or tsDMARDs revealed similar decreases in risk of incident dementia, compared with patients taking bDMARDs or tsDMARDs along with methotrexate at baseline.

“NSAIDs and glucocorticoids have been studied in RCTs [randomized, controlled trials],” Dr. Sattui said in the interview. “Despite initial observational data that showed some signal for improvement, no benefit was observed in either of the RCTs. Other agents with possible anti-inflammatory effects and more benign profiles, such as curcumin, are being studied. There are also ongoing trials looking into the use of JAK [Janus kinase] inhibitors or [interleukin]-1 inhibition in dementia.”

He added: “There is a need to better study the association between cognition and disease activity, as well as treat-to-target strategies, prospectively in patients with RA. It is important to also acknowledge that any of these findings might be just specific for RA, so extrapolation to non-RA individuals might be limited.”

In commenting on the findings of the study, Rishi J. Desai, PhD, assistant professor of medicine in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston, said that “superior inflammation control with biologics or targeted DMARDs is an interesting hypothesis explaining the observed findings. It merits further investigation and replication in diverse populations.” He added: “It should be noted that a key challenge in evaluating this hypothesis using insurance claims data is unavailability of some important factors such as socioeconomic status and patient frailty. These may be driving treatment selection between conventional DMARDs, which are cheaper with more benign adverse-event profiles, and biologic or targeted DMARDs, which are more expensive with a less favorable adverse-event profile.”
 

Prior research

Several studies have investigated the effect of DMARDs, including bDMARDs like tumor necrosis factor inhibitors, on incident dementia in patients with RA.

Among this research is a study by Dr. Desai and colleagues that looked at comparative risk of AD and related dementia in 22,569 Medicare beneficiaries receiving tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors in comparison with abatacept (a T-cell activation inhibitor). No differentiating risk associations were found in this cohort study.

Other past studies include:

• A study comparing about 21,000 patients with RA and a non-RA cohort of about 62,000 found a 37% reduction in dementia development among RA patients receiving DMARDs. The effect was dose dependent, greater with high cumulative dosages, and was found in both men and women and in subgroups younger and older than 65 years.
• A retrospective study of electronic health records from 56 million adult patients identified a subset of patients with RA, psoriasis, ankylosing spondylitis, ulcerative colitis, or Crohn’s disease in whom systemic inflammation increased risk for AD through a mechanism involving TNF. The risk for AD in patients was lowered by treatment with etanercept, adalimumab, infliximab, or methotrexate, with larger reductions observed in younger patients than in older patients receiving TNF blockers.
• A propensity score–matched retrospective cohort study in 2,510 U.S. veterans with RA found that use of a TNF inhibitor reduced the risk of dementia by 36%, compared with control patients (HR, 0.64; 95% CI, 0.52-0.80), and the effect was consistent over 5-20 years post RA diagnosis.
• In a retrospective, multinational, matched, case-control study of patients older than 50 years with RA, prior methotrexate use was associated with lower dementia risk (OR, 0.71; 95% CI, 0.52-0.98). Use of methotrexate longer than 4 years demonstrated the lowest dementia risk (odds ratio, 0.37; 95% CI, 0.17-0.79).

These past studies, Dr. Sattui and colleagues pointed out, have multiple shortcomings, including case-control design, different definitions of exposure or outcomes, and inadequate control of confounders, underscoring the need for more rigorous studies.

Several authors of the CMS claims study disclosed research support, grants, and consulting fees from pharmaceutical companies. The research was supported by a grant from the National Institutes of Health. Dr. Desai disclosed that he has received funding from the National Institute on Aging for drug repurposing studies of dementia.

The incidence of dementia in patients with rheumatoid arthritis who took either a biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) was significantly lower than the rate observed in patients who take only a conventional synthetic DMARD (csDMARD) in a national database study.

The work builds on previous research indicating a higher risk of Alzheimer’s disease and related dementias in people with RA. While joint pain and swelling are the cardinal symptoms of RA, its systemic inflammation leads to multiple systemic manifestations, offering biologically plausible links with cognitive decline. In addition, patients with RA have high prevalence of cardiovascular disease, diabetes, depression, disability, and physical inactivity, all of which are risk factors for dementia.

Chronic neuroinflammation secondary to either intrinsic or systemic stimuli is thought to play a key role in dementia development, especially Alzheimer’s dementia (AD). Research showing a role of tumor necrosis factor–alpha (TNF-alpha) in the development of dementia has piqued interest in a potential protective effect of TNF inhibitors. “TNF-alpha is thought to have an important role in different stages of the pathophysiology and disease progression of Alzheimer’s disease,” study first author Sebastian E. Sattui, MD, assistant professor of medicine at the University of Pittsburgh and director of the University of Pittsburgh Vasculitis Center, said in an interview. “Animal models have shown that TNF inhibition reduces microgliosis, neuronal loss, and tau phosphorylation. Cognitive improvement has been seen in two trials with Alzheimer’s disease patients, but were not in rheumatoid arthritis patients.”

In the newest study, published online in Seminars in Arthritis and Rheumatism, Dr. Sattui and colleagues suggest that a lower risk for dementia seen with bDMARDs and tsDMARDs may be attributable to an overall greater decrease in inflammation rather than any mechanism of action specific to these drugs.

In the study of Centers for Medicare & Medicaid Services claims during 2006-2017 for 141,326 adult patients with RA, the crude incident rates were 2.0 per 100 person-years (95% confidence interval, 1.9-2.1) for patients on csDMARDs and 1.3 (95% CI, 1.2-1.4) for patients on any b/tsDMARD. There were 3,794 cases of incident dementia during follow-up among 233,271 initiations of any DMARD. The adjusted risk for dementia among users of bDMARDs or tsDMARDs was 19% lower than the adjusted risk for patients on csDMARDs (hazard ratio, 0.81; 95% CI, 0.76-0.87). No significant differences were found between classes of bDMARDs or tsDMARDs.

Dr. Sattui and coauthors’ investigation included adults aged at least 40 years with two RA diagnoses by a rheumatologist more than 7 and less than 365 days apart. Those with prior dementia diagnoses were excluded. Their analysis found the risk of incident dementia to be comparable between patients receiving TNF inhibitors (HR, 0.86; 95% CI, 0.80-0.93), non-TNFi bDMARDs (HR, 0.76; 95% CI, 0.70-0.83), and tsDMARDs (HR, 0.69; 95% CI, 0.53-0.90), with csDMARDs as the referent. A second subgroup analysis looking at patients with prior methotrexate use who were taking bDMARDs or tsDMARDs revealed similar decreases in risk of incident dementia, compared with patients taking bDMARDs or tsDMARDs along with methotrexate at baseline.

“NSAIDs and glucocorticoids have been studied in RCTs [randomized, controlled trials],” Dr. Sattui said in the interview. “Despite initial observational data that showed some signal for improvement, no benefit was observed in either of the RCTs. Other agents with possible anti-inflammatory effects and more benign profiles, such as curcumin, are being studied. There are also ongoing trials looking into the use of JAK [Janus kinase] inhibitors or [interleukin]-1 inhibition in dementia.”

He added: “There is a need to better study the association between cognition and disease activity, as well as treat-to-target strategies, prospectively in patients with RA. It is important to also acknowledge that any of these findings might be just specific for RA, so extrapolation to non-RA individuals might be limited.”

In commenting on the findings of the study, Rishi J. Desai, PhD, assistant professor of medicine in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston, said that “superior inflammation control with biologics or targeted DMARDs is an interesting hypothesis explaining the observed findings. It merits further investigation and replication in diverse populations.” He added: “It should be noted that a key challenge in evaluating this hypothesis using insurance claims data is unavailability of some important factors such as socioeconomic status and patient frailty. These may be driving treatment selection between conventional DMARDs, which are cheaper with more benign adverse-event profiles, and biologic or targeted DMARDs, which are more expensive with a less favorable adverse-event profile.”
 

Prior research

Several studies have investigated the effect of DMARDs, including bDMARDs like tumor necrosis factor inhibitors, on incident dementia in patients with RA.

Among this research is a study by Dr. Desai and colleagues that looked at comparative risk of AD and related dementia in 22,569 Medicare beneficiaries receiving tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors in comparison with abatacept (a T-cell activation inhibitor). No differentiating risk associations were found in this cohort study.

Other past studies include:

• A study comparing about 21,000 patients with RA and a non-RA cohort of about 62,000 found a 37% reduction in dementia development among RA patients receiving DMARDs. The effect was dose dependent, greater with high cumulative dosages, and was found in both men and women and in subgroups younger and older than 65 years.
• A retrospective study of electronic health records from 56 million adult patients identified a subset of patients with RA, psoriasis, ankylosing spondylitis, ulcerative colitis, or Crohn’s disease in whom systemic inflammation increased risk for AD through a mechanism involving TNF. The risk for AD in patients was lowered by treatment with etanercept, adalimumab, infliximab, or methotrexate, with larger reductions observed in younger patients than in older patients receiving TNF blockers.
• A propensity score–matched retrospective cohort study in 2,510 U.S. veterans with RA found that use of a TNF inhibitor reduced the risk of dementia by 36%, compared with control patients (HR, 0.64; 95% CI, 0.52-0.80), and the effect was consistent over 5-20 years post RA diagnosis.
• In a retrospective, multinational, matched, case-control study of patients older than 50 years with RA, prior methotrexate use was associated with lower dementia risk (OR, 0.71; 95% CI, 0.52-0.98). Use of methotrexate longer than 4 years demonstrated the lowest dementia risk (odds ratio, 0.37; 95% CI, 0.17-0.79).

These past studies, Dr. Sattui and colleagues pointed out, have multiple shortcomings, including case-control design, different definitions of exposure or outcomes, and inadequate control of confounders, underscoring the need for more rigorous studies.

Several authors of the CMS claims study disclosed research support, grants, and consulting fees from pharmaceutical companies. The research was supported by a grant from the National Institutes of Health. Dr. Desai disclosed that he has received funding from the National Institute on Aging for drug repurposing studies of dementia.

Motherhood can create changes in the body down to the bone, a new study shows.

Female primates who had been pregnant showed lower levels of calcium, magnesium, and phosphorous in their bones, revealing for the first time new ways that females are changed by pregnancy and breastfeeding, according to a study published by PLOS One.

“Our findings provide additional evidence of the profound impact that reproduction has on the female organism, further demonstrating that the skeleton is not a static organ but a dynamic one that changes with life events,” said lead author and New York University doctoral student Paola Cerrito in a news release.

The study evaluated the bones of rhesus macaques, also known as rhesus monkeys, which share 93% of genes with humans, according to the National Primate Research Centers. They have been used in research that paved the way for many medical breakthroughs such as treatments for HIV/AIDS; they’re also used in Alzheimer’s research.

Menopause has long been known to impact bone health, which is tied to calcium and phosphorous levels. This latest research does not address how bone health is affected by pregnancy and lactation but further points to the everchanging state of bones based on life events.

“Our research shows that even before the cessation of fertility, the skeleton responds dynamically to changes in reproductive status,” Ms. Cerrito said. “Moreover, these findings reaffirm the significant impact giving birth has on a female organism – quite simply, evidence of reproduction is ‘written in the bones’ for life.”

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

Motherhood can create changes in the body down to the bone, a new study shows.

Female primates who had been pregnant showed lower levels of calcium, magnesium, and phosphorous in their bones, revealing for the first time new ways that females are changed by pregnancy and breastfeeding, according to a study published by PLOS One.

“Our findings provide additional evidence of the profound impact that reproduction has on the female organism, further demonstrating that the skeleton is not a static organ but a dynamic one that changes with life events,” said lead author and New York University doctoral student Paola Cerrito in a news release.

The study evaluated the bones of rhesus macaques, also known as rhesus monkeys, which share 93% of genes with humans, according to the National Primate Research Centers. They have been used in research that paved the way for many medical breakthroughs such as treatments for HIV/AIDS; they’re also used in Alzheimer’s research.

Menopause has long been known to impact bone health, which is tied to calcium and phosphorous levels. This latest research does not address how bone health is affected by pregnancy and lactation but further points to the everchanging state of bones based on life events.

“Our research shows that even before the cessation of fertility, the skeleton responds dynamically to changes in reproductive status,” Ms. Cerrito said. “Moreover, these findings reaffirm the significant impact giving birth has on a female organism – quite simply, evidence of reproduction is ‘written in the bones’ for life.”

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

Motherhood can create changes in the body down to the bone, a new study shows.

Female primates who had been pregnant showed lower levels of calcium, magnesium, and phosphorous in their bones, revealing for the first time new ways that females are changed by pregnancy and breastfeeding, according to a study published by PLOS One.

“Our findings provide additional evidence of the profound impact that reproduction has on the female organism, further demonstrating that the skeleton is not a static organ but a dynamic one that changes with life events,” said lead author and New York University doctoral student Paola Cerrito in a news release.

The study evaluated the bones of rhesus macaques, also known as rhesus monkeys, which share 93% of genes with humans, according to the National Primate Research Centers. They have been used in research that paved the way for many medical breakthroughs such as treatments for HIV/AIDS; they’re also used in Alzheimer’s research.

Menopause has long been known to impact bone health, which is tied to calcium and phosphorous levels. This latest research does not address how bone health is affected by pregnancy and lactation but further points to the everchanging state of bones based on life events.

“Our research shows that even before the cessation of fertility, the skeleton responds dynamically to changes in reproductive status,” Ms. Cerrito said. “Moreover, these findings reaffirm the significant impact giving birth has on a female organism – quite simply, evidence of reproduction is ‘written in the bones’ for life.”

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

Medicare’s recently announced 2023 physician payment rule likely trims doctors’ pay even as it aims to expand patients’ access to behavioral health services, chronic pain management, and hearing screening. The rule also seeks to ease financial and administrative burdens on accountable care organizations (ACOs).

But physician groups’ initial reactions centered on what the American Medical Association describes as a “damaging across-the-board reduction” of 4.4% in a base calculation, known as a conversion factor.

The reduction is only one of the current threats to physician’s finances, Jack Resneck Jr, MD, AMA’s president, said in a statement. Medicare payment rates also fail to account for inflation in practice costs and COVID-related challenges. Physician’s Medicare payments could be cut by nearly 8.5% in 2023, factoring in other budget cuts, Dr. Resneck said in the statement.

That “would severely impede patient access to care due to the forced closure of physician practices and put further strain on those that remained open during the pandemic,” he said.

A key driver of these cuts is a law that was intended to resolve budget battles between Congress and physicians, while also transitioning Medicare away from fee-for-service payments and pegging reimbursement to judgments about value of care provided. The Centers for Medicare & Medicaid Services thus had little choice about cuts mandated by the Medicare Access and CHIP Reauthorization Act (MACRA) of 2015.

For AMA and other physician groups, the finalization of the Medicare rule served as a rallying point to build support for pending legislation intended to stave off at least some payment cuts.

Federal officials should act soon to block the expected cuts before this season of Congress ends in January, said Anders Gilberg, senior vice president for government affairs at the Medical Group Management Association, in a statement.

“This cannot wait until next Congress – there are claims-processing implications for retroactively applying these policies,” Mr. Gilberg said.

He said MGMA would work with Congress and CMS “to mitigate these cuts and develop sustainable payment policies to allow physician practices to focus on treating patients instead of scrambling to keep their doors open.”
 

Chronic budget battles

Once seen as a promising resolution to chronic annual budget battles between physicians and Medicare, MACRA has proven a near-universal disappointment. A federal advisory commission in 2018 recommended that Congress scrap MACRA’s  Merit-based Incentive Payment System (MIPS) and replace it with a new approach for attempting to tie reimbursement to judgments about the quality of medical care.

MACRA replaced an earlier budgeting approach on Medicare physician pay, known as the sustainable growth rate (SGR). Physician groups successfully lobbied Congress for many years to block threatened Medicare payment cuts. Between 2003 and April 2014, Congress passed 17 laws overriding the cuts to physician pay that the lawmakers earlier mandated through the SGR.

A similar pattern has emerged as Congress now acts on short-term fixes to stave off MACRA-mandated cuts. A law passed last December postponed cuts in physician pay from MACRA and federal budget laws.

And more than 70 members of the House support a bill (HR 8800) intended to block a slated 4.4% MACRA-related cut in physician pay for 2023. Two physicians, Rep. Ami Bera, MD, (D-CA) and Rep. Larry Bucshon (R-IN) sponsored the bill.

Among the groups backing the bill are the AMA, American Academy of Family Physicians, and American College of Physicians. The lawmakers may try to attach this bill to a large spending measure, known as an omnibus, that Congress will try to clear in December to avoid a partial government shutdown.

In a statement, Tochi Iroku-Malize, MD, MPH, MBA, the president of AAFP, urged Congress to factor in inflation in setting physician reimbursement and to reconsider Medicare’s approach to paying physicians.

“It’s past time to end the untenable physician payment cuts – which have now become an annual threat to the stability of physician practices – caused by Medicare budget neutrality requirements and the ongoing freeze in annual payment updates,” Dr. Iroku-Malize said.

Congress also needs to retool its approach to alternative payment models (APMs) intended to improve the quality of patient care, Dr. Iroku-Malize said.

“Physicians in APMs are better equipped to address unmet social needs and provide other enhanced services that are not supported by fee-for-service payment rates,” Dr. Iroku-Malize said. “However, insufficient Medicare fee-for-service payment rates, inadequate support, and burdensome timelines are undermining the move to value-based care and exacerbating our nation’s underinvestment in primary care.”
 

Policy changes

But the new rule did have some good news for family physicians, Dr. Iroku-Malize told this news organization in an email.

CMS said it will pay psychologists and social workers to help manage behavioral health needs as part of the primary care team, in addition to their own services. This change will give primary care practices more flexibility to coordinate with behavioral health professionals, Dr. Iroku-Malize noted.

“We know that primary care physicians are the first point of contact for many patients, and behavioral health integration increases critical access to mental health care, decreases stigma for patients, and can prevent more severe medical and behavioral health events,” she wrote.

CMS also eased a supervision requirement for nonphysicians providing behavioral health services.

It intends to allow certain health professionals to provide this care without requiring that a supervising physician or nurse practitioner be physically on site. This shift from direct supervision to what’s called general supervision applies to marriage and family therapists, licensed professional counselors, addiction counselors, certified peer recovery specialists, and behavioral health specialists, CMS said.

Other major policy changes include:

Medicare will pay for telehealth opioid treatment programs allowing patients to initiate treatment with buprenorphine. CMS also clarified that certain programs can bill for opioid use disorder treatment services provided through mobile units, such as vans.

Medicare enrollees may see audiologists for nonacute hearing conditions without an order from a physician or nurse practitioner. The policy is meant to allow audiologists to examine patients to prescribe, fit, or change hearing aids, or to provide hearing tests unrelated to disequilibrium.

CMS created new reimbursement codes for chronic pain management and treatment services to encourage clinicians to see patients with this condition. The codes also are meant to encourage practitioners already treating Medicare patients with chronic pain to spend more time helping them manage their condition “within a trusting, supportive, and ongoing care partnership,” CMS said.

CMS also made changes to the Medicare Shared Savings Program (MSSP) intended to reduce administrative burdens and offer more financial support to practices involved in ACOs. These steps include expanding opportunities for certain low-revenue ACOs to share in savings even if they do not meet a target rate.

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

ORLANDO – Treatment with a renin-angiotensin system (RAS) inhibitor is widely accepted as standard practice for slowing progression of chronic kidney disease (CKD), but data have been inconsistent as to whether there is benefit to continuing RAS inhibition when patients develop advanced CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m².

Now, in STOP ACEi, a new multicenter, randomized trial of 411 patients, maintaining treatment with a RAS inhibitor in adults with advanced and progressive CKD did not cause a clinically relevant change in kidney function, or in the long-term rate of decline in kidney function, compared with stopping treatment, for 3 years.

People who continued RAS inhibitor treatment did not develop a significant or clinically relevant decrease in eGFR, the study’s primary outcome, both overall as well as in several prespecified subgroups compared with those who discontinued treatment, said Sunil Bhandari, MBChB, PhD, and associates, who presented the research in a poster at the annual meeting of the American Society of Nephrology.

“I hope these results will reassure clinicians to continue ACE inhibitors or ARBs” in patients with advanced CKD, “with their known beneficial cardiovascular effects,” Dr. Bhandari said in an interview.

The results were simultaneously published in the New England Journal of Medicine.
 

Similar eGFR levels after 3 years

While it’s clear that in patients with mild or moderate CKD, treatment with a RAS inhibitor, which includes angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), reduces blood pressure, slows decline in eGFR, reduces proteinuria, and delays progression to advanced CKD, there has been little evidence that the use of RAS inhibitors benefits patients with advanced CKD.

Data from previous trials have been inconsistent regarding whether the use of RAS inhibitors is nephroprotective in patients with advanced CKD, say Dr. Bhandari, a nephrologist and professor at Hull York Medical School, Hull, England, and colleagues.

“Current guidelines do not provide specific advice on whether to continue or stop ACE inhibitors or ARBs for advanced chronic kidney disease,” they also note.

And so they decided to assess whether discontinuation of ACE inhibitors/ARBs could slow progression of CKD in patients with advanced CKD.

Three years after 206 study participants stopped RAS inhibitor treatment, the least-squares mean eGFR was 12.6 mL/min per 1.73m² in the discontinuation group and 13.3 mL/min per 1.73 m² in the 205 patients in the continuation group, a difference that was not significant.

In addition to the primary outcome, 62% of patients who stopped RAS inhibitor treatment and 56% of those who continued developed end-stage kidney disease or required renal-replacement therapy, which translated into an adjusted hazard ratio of 1.28 for this outcome among those who discontinued compared with those who continued, which was just short of significance (95% CI, 0.99-1.65).

The two study groups also showed no significant differences in the 3-year incidence of hospitalization for any reason, cardiovascular events, or deaths. The two groups also showed no meaningful differences in various domains of quality of life and no differences in serious adverse effects.
 

Participants had an eGFR less than 30 mL/min per 1.73 m²

The study ran at 39 United Kingdom centers in 2014-2019. Investigators enrolled adults with an eGFR of less than 30 mL/min per 1.73 m² who were not on dialysis and had not received a kidney transplant. In addition, all enrolled patients had to have an annual drop in eGFR of more than 2 mL/min per 1.73 m² during the prior 2 years and had to have been on treatment with at least one RAS inhibitor for more than 6 months.

The randomization protocol insured balanced distribution of subjects between the two study arms by age, eGFR, presence of diabetes, and level of proteinuria, among other factors. The study design also mandated that participants maintain a blood pressure of no more than 140/85 mm Hg.

Those who discontinued RAS-inhibitor treatment could receive any guideline-recommended antihypertensive agent that was not a RAS inhibitor, although adding a RAS inhibitor was permitted as a last treatment resort.

People in the maintenance group could receive whichever additional antihypertensive agents their treating clinicians deemed necessary for maintaining the target blood pressure.

The enrolled population was a median age of 63 years old and 68% were men. Their average eGFR at baseline was 18 mL/min per 1.73 m², and 118 (29%) had an eGFR of less than 15 mL/min per 1.73 m². Their median level of proteinuria was 115 mg/mmol (about 1,018 mg/g). Diabetes was prevalent in 37%, and 58% of participants were taking at least three antihypertensive medications at entry.

Among the study’s limitations, the researchers cited the open-label design, which may have affected clinical care and the tally of subjective endpoints, including quality of life and exercise capacity. Also, because the study enrolled people who were on a RAS inhibitor at the time of randomization, it did not include anyone who had already discontinued these agents.
 

Continue RAS inhibitors in advanced CKD for best outcomes

Dr. Bhandari and colleagues note that in a large observational trial published in January 2021, Swedish researchers found an increase in the incidence of major cardiovascular events and death among patients with advanced CKD who had discontinued RAS inhibitors.

But they observe, “Our trial did not have sufficient power to investigate the effect of the discontinuation of RAS inhibitors on cardiovascular events or mortality. However, because our findings are consistent with a lack of advantage for such discontinuation with respect to kidney function, there is little rationale to conduct a larger randomized trial to investigate cardiovascular safety.”

“Our findings do not support the hypothesis that the discontinuation of RAS inhibitors in patients with advanced and progressive chronic kidney disease would improve kidney function, quality of life, or exercise capacity.”

“The results of this trial will inform future clinical practice worldwide and guideline recommendations,” they conclude.

STOP ACEi received no commercial funding. Dr. Bhandari has reported no relevant financial relationships.

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

ORLANDO – Treatment with a renin-angiotensin system (RAS) inhibitor is widely accepted as standard practice for slowing progression of chronic kidney disease (CKD), but data have been inconsistent as to whether there is benefit to continuing RAS inhibition when patients develop advanced CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m².

Now, in STOP ACEi, a new multicenter, randomized trial of 411 patients, maintaining treatment with a RAS inhibitor in adults with advanced and progressive CKD did not cause a clinically relevant change in kidney function, or in the long-term rate of decline in kidney function, compared with stopping treatment, for 3 years.

People who continued RAS inhibitor treatment did not develop a significant or clinically relevant decrease in eGFR, the study’s primary outcome, both overall as well as in several prespecified subgroups compared with those who discontinued treatment, said Sunil Bhandari, MBChB, PhD, and associates, who presented the research in a poster at the annual meeting of the American Society of Nephrology.

“I hope these results will reassure clinicians to continue ACE inhibitors or ARBs” in patients with advanced CKD, “with their known beneficial cardiovascular effects,” Dr. Bhandari said in an interview.

The results were simultaneously published in the New England Journal of Medicine.
 

Similar eGFR levels after 3 years

While it’s clear that in patients with mild or moderate CKD, treatment with a RAS inhibitor, which includes angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), reduces blood pressure, slows decline in eGFR, reduces proteinuria, and delays progression to advanced CKD, there has been little evidence that the use of RAS inhibitors benefits patients with advanced CKD.

Data from previous trials have been inconsistent regarding whether the use of RAS inhibitors is nephroprotective in patients with advanced CKD, say Dr. Bhandari, a nephrologist and professor at Hull York Medical School, Hull, England, and colleagues.

“Current guidelines do not provide specific advice on whether to continue or stop ACE inhibitors or ARBs for advanced chronic kidney disease,” they also note.

And so they decided to assess whether discontinuation of ACE inhibitors/ARBs could slow progression of CKD in patients with advanced CKD.

Three years after 206 study participants stopped RAS inhibitor treatment, the least-squares mean eGFR was 12.6 mL/min per 1.73m² in the discontinuation group and 13.3 mL/min per 1.73 m² in the 205 patients in the continuation group, a difference that was not significant.

In addition to the primary outcome, 62% of patients who stopped RAS inhibitor treatment and 56% of those who continued developed end-stage kidney disease or required renal-replacement therapy, which translated into an adjusted hazard ratio of 1.28 for this outcome among those who discontinued compared with those who continued, which was just short of significance (95% CI, 0.99-1.65).

The two study groups also showed no significant differences in the 3-year incidence of hospitalization for any reason, cardiovascular events, or deaths. The two groups also showed no meaningful differences in various domains of quality of life and no differences in serious adverse effects.
 

Participants had an eGFR less than 30 mL/min per 1.73 m²

The study ran at 39 United Kingdom centers in 2014-2019. Investigators enrolled adults with an eGFR of less than 30 mL/min per 1.73 m² who were not on dialysis and had not received a kidney transplant. In addition, all enrolled patients had to have an annual drop in eGFR of more than 2 mL/min per 1.73 m² during the prior 2 years and had to have been on treatment with at least one RAS inhibitor for more than 6 months.

The randomization protocol insured balanced distribution of subjects between the two study arms by age, eGFR, presence of diabetes, and level of proteinuria, among other factors. The study design also mandated that participants maintain a blood pressure of no more than 140/85 mm Hg.

Those who discontinued RAS-inhibitor treatment could receive any guideline-recommended antihypertensive agent that was not a RAS inhibitor, although adding a RAS inhibitor was permitted as a last treatment resort.

People in the maintenance group could receive whichever additional antihypertensive agents their treating clinicians deemed necessary for maintaining the target blood pressure.

The enrolled population was a median age of 63 years old and 68% were men. Their average eGFR at baseline was 18 mL/min per 1.73 m², and 118 (29%) had an eGFR of less than 15 mL/min per 1.73 m². Their median level of proteinuria was 115 mg/mmol (about 1,018 mg/g). Diabetes was prevalent in 37%, and 58% of participants were taking at least three antihypertensive medications at entry.

Among the study’s limitations, the researchers cited the open-label design, which may have affected clinical care and the tally of subjective endpoints, including quality of life and exercise capacity. Also, because the study enrolled people who were on a RAS inhibitor at the time of randomization, it did not include anyone who had already discontinued these agents.
 

Continue RAS inhibitors in advanced CKD for best outcomes

Dr. Bhandari and colleagues note that in a large observational trial published in January 2021, Swedish researchers found an increase in the incidence of major cardiovascular events and death among patients with advanced CKD who had discontinued RAS inhibitors.

But they observe, “Our trial did not have sufficient power to investigate the effect of the discontinuation of RAS inhibitors on cardiovascular events or mortality. However, because our findings are consistent with a lack of advantage for such discontinuation with respect to kidney function, there is little rationale to conduct a larger randomized trial to investigate cardiovascular safety.”

“Our findings do not support the hypothesis that the discontinuation of RAS inhibitors in patients with advanced and progressive chronic kidney disease would improve kidney function, quality of life, or exercise capacity.”

“The results of this trial will inform future clinical practice worldwide and guideline recommendations,” they conclude.

STOP ACEi received no commercial funding. Dr. Bhandari has reported no relevant financial relationships.

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

ORLANDO – Treatment with a renin-angiotensin system (RAS) inhibitor is widely accepted as standard practice for slowing progression of chronic kidney disease (CKD), but data have been inconsistent as to whether there is benefit to continuing RAS inhibition when patients develop advanced CKD, defined as an estimated glomerular filtration rate (eGFR) of less than 30 mL/min per 1.73 m².

Now, in STOP ACEi, a new multicenter, randomized trial of 411 patients, maintaining treatment with a RAS inhibitor in adults with advanced and progressive CKD did not cause a clinically relevant change in kidney function, or in the long-term rate of decline in kidney function, compared with stopping treatment, for 3 years.

People who continued RAS inhibitor treatment did not develop a significant or clinically relevant decrease in eGFR, the study’s primary outcome, both overall as well as in several prespecified subgroups compared with those who discontinued treatment, said Sunil Bhandari, MBChB, PhD, and associates, who presented the research in a poster at the annual meeting of the American Society of Nephrology.

“I hope these results will reassure clinicians to continue ACE inhibitors or ARBs” in patients with advanced CKD, “with their known beneficial cardiovascular effects,” Dr. Bhandari said in an interview.

The results were simultaneously published in the New England Journal of Medicine.
 

Similar eGFR levels after 3 years

While it’s clear that in patients with mild or moderate CKD, treatment with a RAS inhibitor, which includes angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), reduces blood pressure, slows decline in eGFR, reduces proteinuria, and delays progression to advanced CKD, there has been little evidence that the use of RAS inhibitors benefits patients with advanced CKD.

Data from previous trials have been inconsistent regarding whether the use of RAS inhibitors is nephroprotective in patients with advanced CKD, say Dr. Bhandari, a nephrologist and professor at Hull York Medical School, Hull, England, and colleagues.

“Current guidelines do not provide specific advice on whether to continue or stop ACE inhibitors or ARBs for advanced chronic kidney disease,” they also note.

And so they decided to assess whether discontinuation of ACE inhibitors/ARBs could slow progression of CKD in patients with advanced CKD.

Three years after 206 study participants stopped RAS inhibitor treatment, the least-squares mean eGFR was 12.6 mL/min per 1.73m² in the discontinuation group and 13.3 mL/min per 1.73 m² in the 205 patients in the continuation group, a difference that was not significant.

In addition to the primary outcome, 62% of patients who stopped RAS inhibitor treatment and 56% of those who continued developed end-stage kidney disease or required renal-replacement therapy, which translated into an adjusted hazard ratio of 1.28 for this outcome among those who discontinued compared with those who continued, which was just short of significance (95% CI, 0.99-1.65).

The two study groups also showed no significant differences in the 3-year incidence of hospitalization for any reason, cardiovascular events, or deaths. The two groups also showed no meaningful differences in various domains of quality of life and no differences in serious adverse effects.
 

Participants had an eGFR less than 30 mL/min per 1.73 m²

The study ran at 39 United Kingdom centers in 2014-2019. Investigators enrolled adults with an eGFR of less than 30 mL/min per 1.73 m² who were not on dialysis and had not received a kidney transplant. In addition, all enrolled patients had to have an annual drop in eGFR of more than 2 mL/min per 1.73 m² during the prior 2 years and had to have been on treatment with at least one RAS inhibitor for more than 6 months.

The randomization protocol insured balanced distribution of subjects between the two study arms by age, eGFR, presence of diabetes, and level of proteinuria, among other factors. The study design also mandated that participants maintain a blood pressure of no more than 140/85 mm Hg.

Those who discontinued RAS-inhibitor treatment could receive any guideline-recommended antihypertensive agent that was not a RAS inhibitor, although adding a RAS inhibitor was permitted as a last treatment resort.

People in the maintenance group could receive whichever additional antihypertensive agents their treating clinicians deemed necessary for maintaining the target blood pressure.

The enrolled population was a median age of 63 years old and 68% were men. Their average eGFR at baseline was 18 mL/min per 1.73 m², and 118 (29%) had an eGFR of less than 15 mL/min per 1.73 m². Their median level of proteinuria was 115 mg/mmol (about 1,018 mg/g). Diabetes was prevalent in 37%, and 58% of participants were taking at least three antihypertensive medications at entry.

Among the study’s limitations, the researchers cited the open-label design, which may have affected clinical care and the tally of subjective endpoints, including quality of life and exercise capacity. Also, because the study enrolled people who were on a RAS inhibitor at the time of randomization, it did not include anyone who had already discontinued these agents.
 

Continue RAS inhibitors in advanced CKD for best outcomes

Dr. Bhandari and colleagues note that in a large observational trial published in January 2021, Swedish researchers found an increase in the incidence of major cardiovascular events and death among patients with advanced CKD who had discontinued RAS inhibitors.

But they observe, “Our trial did not have sufficient power to investigate the effect of the discontinuation of RAS inhibitors on cardiovascular events or mortality. However, because our findings are consistent with a lack of advantage for such discontinuation with respect to kidney function, there is little rationale to conduct a larger randomized trial to investigate cardiovascular safety.”

“Our findings do not support the hypothesis that the discontinuation of RAS inhibitors in patients with advanced and progressive chronic kidney disease would improve kidney function, quality of life, or exercise capacity.”

“The results of this trial will inform future clinical practice worldwide and guideline recommendations,” they conclude.

STOP ACEi received no commercial funding. Dr. Bhandari has reported no relevant financial relationships.

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

Therapeutic drug monitoring allowed patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis to reduce their dosage of tumor necrosis factor–alpha (TNF) inhibitors, based on data from 239 individuals.

Use of TNF-alpha inhibitors improves treatment response for many arthritis patients but dosage is rarely adjusted on an individual level, which may lead to unnecessary overdosing in some patients, Mogens Pfeiffer-Jensen, MD, of Aarhus (Denmark) University Hospital, and colleagues wrote.

Data from previous studies suggest that therapeutic drug monitoring (TDM) based on serum trough levels may allow for dose optimization and dose reduction in inflammatory bowel disease patients, but data in patients with arthritis are lacking, they wrote.

In a study published in the Scandinavian Journal of Rheumatology, the researchers recruited 99 patients with RA, 48 with psoriatic arthritis (PsA), and 92 with spondyloarthritis (SpA). The participants were randomized to standard care or standard care plus TDM. Serum trough levels were assessed at baseline and at every 4 months, and prescription changes or drug switches were implemented based on these levels. At baseline, 81 patients were being treated with infliximab (Remicade and biosimilars), 79 with etanercept (Enbrel), and 79 with adalimumab (Humira).

The primary endpoint was reduced drug prescription after 48 weeks.

Overall, TDM significantly reduced prescription of infliximab by 12% (P = .001) and prescription of etanercept by 15% (P = .01), compared with standard care. TDM also prolonged the interdosing intervals of etanercept by 235% (P = .02) and of adalimumab by 28% (P = .04), compared with standard care.

TDM patients taking infliximab had more frequent dose reduction and less frequent dose increases during and after the study when compared with patients who stayed with standard care; similar trends were seen with adalimumab. TDM also accelerated the switch to other biologics for patients on all three medications.

No significant differences occurred in adverse events or hospitalizations between the TDM and standard care patients.

Clinical composite scores (Disease Activity Score based on 28 joints with C-reactive protein) were reduced in patients with RA and PsA who were taking adalimumab and randomized to TDM, but no other clinical outcome differences were noted. Scores on the Health Assessment Questionnaire and global Visual Analog Scale for pain were significantly lower in patients in the TDM group who were taking infliximab and adalimumab, “indicating equally or superior sustained remission across diagnoses,” the researchers emphasized.

The findings were limited by several factors, including the variations in pathophysiology and open-label design. “However, since the TDM was based on an objective serum value and decision procedures were clear, we do not consider the potential of unconscious bias to outweigh the benefits of dose-changing abilities,” they wrote.

The researchers expressed surprise that the reduced use of TNF-alpha inhibitors did not significantly reduce adverse events or serious adverse events, compared with standard care, but they proposed that standard of care may have taken adverse events into account, because all patients had received prescriptions at least 3 months before the study.

As for clinical implications, the current costs of the biochemical assays necessary for TDM may be a barrier to implementing TDM as a standard part of daily clinical practice, the researchers added. However, the study was strengthened by the inclusion of patients with RA, PsA, and SpA, and is the first known to include patients receiving etanercept or adalimumab in an examination of TDM.

“Our data support TDM based solely on serum trough levels in [TNF-alpha inhibitors] with different pharmacokinetics as a future key player in personalized medicine for chronic rheumatoid diseases treated with biologics,” they concluded.

The study was supported by Spydspidspuljen, Region Midt, Denmark, and Department of Rheumatology, Aarhus University Hospital. The researchers had no financial conflicts to disclose. 

Therapeutic drug monitoring allowed patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis to reduce their dosage of tumor necrosis factor–alpha (TNF) inhibitors, based on data from 239 individuals.

Use of TNF-alpha inhibitors improves treatment response for many arthritis patients but dosage is rarely adjusted on an individual level, which may lead to unnecessary overdosing in some patients, Mogens Pfeiffer-Jensen, MD, of Aarhus (Denmark) University Hospital, and colleagues wrote.

Data from previous studies suggest that therapeutic drug monitoring (TDM) based on serum trough levels may allow for dose optimization and dose reduction in inflammatory bowel disease patients, but data in patients with arthritis are lacking, they wrote.

In a study published in the Scandinavian Journal of Rheumatology, the researchers recruited 99 patients with RA, 48 with psoriatic arthritis (PsA), and 92 with spondyloarthritis (SpA). The participants were randomized to standard care or standard care plus TDM. Serum trough levels were assessed at baseline and at every 4 months, and prescription changes or drug switches were implemented based on these levels. At baseline, 81 patients were being treated with infliximab (Remicade and biosimilars), 79 with etanercept (Enbrel), and 79 with adalimumab (Humira).

The primary endpoint was reduced drug prescription after 48 weeks.

Overall, TDM significantly reduced prescription of infliximab by 12% (P = .001) and prescription of etanercept by 15% (P = .01), compared with standard care. TDM also prolonged the interdosing intervals of etanercept by 235% (P = .02) and of adalimumab by 28% (P = .04), compared with standard care.

TDM patients taking infliximab had more frequent dose reduction and less frequent dose increases during and after the study when compared with patients who stayed with standard care; similar trends were seen with adalimumab. TDM also accelerated the switch to other biologics for patients on all three medications.

No significant differences occurred in adverse events or hospitalizations between the TDM and standard care patients.

Clinical composite scores (Disease Activity Score based on 28 joints with C-reactive protein) were reduced in patients with RA and PsA who were taking adalimumab and randomized to TDM, but no other clinical outcome differences were noted. Scores on the Health Assessment Questionnaire and global Visual Analog Scale for pain were significantly lower in patients in the TDM group who were taking infliximab and adalimumab, “indicating equally or superior sustained remission across diagnoses,” the researchers emphasized.

The findings were limited by several factors, including the variations in pathophysiology and open-label design. “However, since the TDM was based on an objective serum value and decision procedures were clear, we do not consider the potential of unconscious bias to outweigh the benefits of dose-changing abilities,” they wrote.

The researchers expressed surprise that the reduced use of TNF-alpha inhibitors did not significantly reduce adverse events or serious adverse events, compared with standard care, but they proposed that standard of care may have taken adverse events into account, because all patients had received prescriptions at least 3 months before the study.

As for clinical implications, the current costs of the biochemical assays necessary for TDM may be a barrier to implementing TDM as a standard part of daily clinical practice, the researchers added. However, the study was strengthened by the inclusion of patients with RA, PsA, and SpA, and is the first known to include patients receiving etanercept or adalimumab in an examination of TDM.

“Our data support TDM based solely on serum trough levels in [TNF-alpha inhibitors] with different pharmacokinetics as a future key player in personalized medicine for chronic rheumatoid diseases treated with biologics,” they concluded.

The study was supported by Spydspidspuljen, Region Midt, Denmark, and Department of Rheumatology, Aarhus University Hospital. The researchers had no financial conflicts to disclose. 

Therapeutic drug monitoring allowed patients with rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis to reduce their dosage of tumor necrosis factor–alpha (TNF) inhibitors, based on data from 239 individuals.

Use of TNF-alpha inhibitors improves treatment response for many arthritis patients but dosage is rarely adjusted on an individual level, which may lead to unnecessary overdosing in some patients, Mogens Pfeiffer-Jensen, MD, of Aarhus (Denmark) University Hospital, and colleagues wrote.

Data from previous studies suggest that therapeutic drug monitoring (TDM) based on serum trough levels may allow for dose optimization and dose reduction in inflammatory bowel disease patients, but data in patients with arthritis are lacking, they wrote.

In a study published in the Scandinavian Journal of Rheumatology, the researchers recruited 99 patients with RA, 48 with psoriatic arthritis (PsA), and 92 with spondyloarthritis (SpA). The participants were randomized to standard care or standard care plus TDM. Serum trough levels were assessed at baseline and at every 4 months, and prescription changes or drug switches were implemented based on these levels. At baseline, 81 patients were being treated with infliximab (Remicade and biosimilars), 79 with etanercept (Enbrel), and 79 with adalimumab (Humira).

The primary endpoint was reduced drug prescription after 48 weeks.

Overall, TDM significantly reduced prescription of infliximab by 12% (P = .001) and prescription of etanercept by 15% (P = .01), compared with standard care. TDM also prolonged the interdosing intervals of etanercept by 235% (P = .02) and of adalimumab by 28% (P = .04), compared with standard care.

TDM patients taking infliximab had more frequent dose reduction and less frequent dose increases during and after the study when compared with patients who stayed with standard care; similar trends were seen with adalimumab. TDM also accelerated the switch to other biologics for patients on all three medications.

No significant differences occurred in adverse events or hospitalizations between the TDM and standard care patients.

Clinical composite scores (Disease Activity Score based on 28 joints with C-reactive protein) were reduced in patients with RA and PsA who were taking adalimumab and randomized to TDM, but no other clinical outcome differences were noted. Scores on the Health Assessment Questionnaire and global Visual Analog Scale for pain were significantly lower in patients in the TDM group who were taking infliximab and adalimumab, “indicating equally or superior sustained remission across diagnoses,” the researchers emphasized.

The findings were limited by several factors, including the variations in pathophysiology and open-label design. “However, since the TDM was based on an objective serum value and decision procedures were clear, we do not consider the potential of unconscious bias to outweigh the benefits of dose-changing abilities,” they wrote.

The researchers expressed surprise that the reduced use of TNF-alpha inhibitors did not significantly reduce adverse events or serious adverse events, compared with standard care, but they proposed that standard of care may have taken adverse events into account, because all patients had received prescriptions at least 3 months before the study.

As for clinical implications, the current costs of the biochemical assays necessary for TDM may be a barrier to implementing TDM as a standard part of daily clinical practice, the researchers added. However, the study was strengthened by the inclusion of patients with RA, PsA, and SpA, and is the first known to include patients receiving etanercept or adalimumab in an examination of TDM.

“Our data support TDM based solely on serum trough levels in [TNF-alpha inhibitors] with different pharmacokinetics as a future key player in personalized medicine for chronic rheumatoid diseases treated with biologics,” they concluded.

The study was supported by Spydspidspuljen, Region Midt, Denmark, and Department of Rheumatology, Aarhus University Hospital. The researchers had no financial conflicts to disclose. 

ORLANDO – The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) significantly slowed progression of renal dysfunction or death from cardiovascular causes among patients with chronic kidney disease (CKD) who did not have diabetes or heart failure in a pivotal trial with more than 6,600 patients.

This confirms the efficacy for this population that was previously seen with dapagliflozin, another agent from the same class, in the DAPA-CKD trial.

In the new trial, EMPA-Kidney, treatment with empagliflozin 10 mg daily for a median of 2.0 years led to a significant 28% relative risk reduction in the primary combined endpoint in comparison with placebo, William G. Herrington, MD, reported at the annual meeting of the American Society of Nephrology.

The results were simultaneously published in the New England Journal of Medicine.

In 2020, a different team of researchers running DAPA-CKD reported that during a median of 2.4 years, treatment of 4,304 patients with dapagliflozin 10 mg daily resulted in a significant 39% relative risk reduction, compared with placebo for an identical combined primary endpoint. Enrollment criteria for the DAPA-CKD trial were mostly similar to that of the current trial.

‘Remarkably similar’ findings

Results from EMPA-Kidney and DAPA-CKD are “remarkably similar,” said Dr. Herrington during a press briefing at the meeting.

He also noted that when the EMPA-Kidney study began – before results from DAPA-CKD were known – “we never imagined such a large effect” on important endpoints in people with CKD.

In addition to cardiovascular death, the combined primary endpoint included the incidence of renal death, incident end-stage kidney disease, a sustained decrease in estimated glomerular filtration rate to less than 10 mL/min per 1.73m², or a sustained decrease in eGFR of at least 40% from baseline.

Having similar evidence from both trials “will hopefully provide people with the confidence to start to use SGLT2 inhibitors as standard care in people with CKD” who match enrollment criteria of the two trials, added Dr. Herrington, a nephrologist at the University of Oxford (England).

The analyses he reported also showed that empagliflozin had similar efficacy for the primary endpoint regardless of whether patients had type 2 diabetes at the time of enrollment and regardless of their eGFR at entry.

To enter EMPA-Kidney, people needed to have either an eGFR of 20-44 mL/min per 1.73m² with no minimum level of albuminuria or an eGFR of 45-89 mL/min per 1.73m² with a urine albumin-to-creatinine ratio (UACR) of at least 200 mg/g.

In contrast, to enroll in DAPA-CKD, patients had to have a UACR of at least 200 mg/g. This means that for the first time, EMPA-Kidney produced data on the relationship between albuminuria severity and the impact of treatment with an SGLT2 inhibitor in the enrolled population.

A signal of greater efficacy with higher UACR

A total of 6,609 patients underwent randomization in EMPA-Kidney. During a median of 2.0 years of follow-up, the primary endpoint – progression of kidney disease or death from cardiovascular causes – occurred in 432 of 3,304 patients (13.1%) in the empagliflozin group and in 558 of 3,305 patients (16.9%) in the placebo group (hazard ratio, 0.72; P < .001).

The results “suggested that the effects [of empagliflozin] are greater in patients with higher levels of albuminuria, with statistically significant heterogeneity between this subgroup and those with a UACR of less than 200 mg/g (P = .02),” Dr. Herrington said.

Of the study population, 54% had no evidence of diabetes at enrollment.

Having data from a second large trial of an SGLT2 inhibitor that included people with isolated CKD who did not have diabetes or heart failure “will start to move the needle” on using this class of drugs in these types of patients, commented F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn.

On the basis of the DAPA-CKD results, in April 2021 the Food and Drug Administration expanded dapagliflozin’s indications to include CKD, yet, “a lot of nephrologists consider SGLT2 inhibitors to be agents for people with diabetes or heart failure, and they defer prescribing them to endocrinologists and cardiologists,” Dr. Wilson said in an interview.

‘Flozinators’ rising

But Pascale H. Lane, MD, a pediatric nephrologist at the University of Oklahoma Health Sciences Center, Oklahoma City, commented that many nephrologists she knows have been prescribing dapagliflozin “widely” to their patients with CKD.

“I know many adult nephrologists who use it almost universally now,” Dr. Lane said. “They call themselves ‘flozinators.’ ”

EMPA-Kidney was sponsored by Boehringer Ingelheim, the company that along with Lilly markets empagliflozin (Jardiance). Dr. Herrington, Dr. Wilson, and Dr. Lane disclosed no relevant financial relationships.

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

ORLANDO – The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) significantly slowed progression of renal dysfunction or death from cardiovascular causes among patients with chronic kidney disease (CKD) who did not have diabetes or heart failure in a pivotal trial with more than 6,600 patients.

This confirms the efficacy for this population that was previously seen with dapagliflozin, another agent from the same class, in the DAPA-CKD trial.

In the new trial, EMPA-Kidney, treatment with empagliflozin 10 mg daily for a median of 2.0 years led to a significant 28% relative risk reduction in the primary combined endpoint in comparison with placebo, William G. Herrington, MD, reported at the annual meeting of the American Society of Nephrology.

The results were simultaneously published in the New England Journal of Medicine.

In 2020, a different team of researchers running DAPA-CKD reported that during a median of 2.4 years, treatment of 4,304 patients with dapagliflozin 10 mg daily resulted in a significant 39% relative risk reduction, compared with placebo for an identical combined primary endpoint. Enrollment criteria for the DAPA-CKD trial were mostly similar to that of the current trial.

‘Remarkably similar’ findings

Results from EMPA-Kidney and DAPA-CKD are “remarkably similar,” said Dr. Herrington during a press briefing at the meeting.

He also noted that when the EMPA-Kidney study began – before results from DAPA-CKD were known – “we never imagined such a large effect” on important endpoints in people with CKD.

In addition to cardiovascular death, the combined primary endpoint included the incidence of renal death, incident end-stage kidney disease, a sustained decrease in estimated glomerular filtration rate to less than 10 mL/min per 1.73m², or a sustained decrease in eGFR of at least 40% from baseline.

Having similar evidence from both trials “will hopefully provide people with the confidence to start to use SGLT2 inhibitors as standard care in people with CKD” who match enrollment criteria of the two trials, added Dr. Herrington, a nephrologist at the University of Oxford (England).

The analyses he reported also showed that empagliflozin had similar efficacy for the primary endpoint regardless of whether patients had type 2 diabetes at the time of enrollment and regardless of their eGFR at entry.

To enter EMPA-Kidney, people needed to have either an eGFR of 20-44 mL/min per 1.73m² with no minimum level of albuminuria or an eGFR of 45-89 mL/min per 1.73m² with a urine albumin-to-creatinine ratio (UACR) of at least 200 mg/g.

In contrast, to enroll in DAPA-CKD, patients had to have a UACR of at least 200 mg/g. This means that for the first time, EMPA-Kidney produced data on the relationship between albuminuria severity and the impact of treatment with an SGLT2 inhibitor in the enrolled population.

A signal of greater efficacy with higher UACR

A total of 6,609 patients underwent randomization in EMPA-Kidney. During a median of 2.0 years of follow-up, the primary endpoint – progression of kidney disease or death from cardiovascular causes – occurred in 432 of 3,304 patients (13.1%) in the empagliflozin group and in 558 of 3,305 patients (16.9%) in the placebo group (hazard ratio, 0.72; P < .001).

The results “suggested that the effects [of empagliflozin] are greater in patients with higher levels of albuminuria, with statistically significant heterogeneity between this subgroup and those with a UACR of less than 200 mg/g (P = .02),” Dr. Herrington said.

Of the study population, 54% had no evidence of diabetes at enrollment.

Having data from a second large trial of an SGLT2 inhibitor that included people with isolated CKD who did not have diabetes or heart failure “will start to move the needle” on using this class of drugs in these types of patients, commented F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn.

On the basis of the DAPA-CKD results, in April 2021 the Food and Drug Administration expanded dapagliflozin’s indications to include CKD, yet, “a lot of nephrologists consider SGLT2 inhibitors to be agents for people with diabetes or heart failure, and they defer prescribing them to endocrinologists and cardiologists,” Dr. Wilson said in an interview.

‘Flozinators’ rising

But Pascale H. Lane, MD, a pediatric nephrologist at the University of Oklahoma Health Sciences Center, Oklahoma City, commented that many nephrologists she knows have been prescribing dapagliflozin “widely” to their patients with CKD.

“I know many adult nephrologists who use it almost universally now,” Dr. Lane said. “They call themselves ‘flozinators.’ ”

EMPA-Kidney was sponsored by Boehringer Ingelheim, the company that along with Lilly markets empagliflozin (Jardiance). Dr. Herrington, Dr. Wilson, and Dr. Lane disclosed no relevant financial relationships.

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

ORLANDO – The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) significantly slowed progression of renal dysfunction or death from cardiovascular causes among patients with chronic kidney disease (CKD) who did not have diabetes or heart failure in a pivotal trial with more than 6,600 patients.

This confirms the efficacy for this population that was previously seen with dapagliflozin, another agent from the same class, in the DAPA-CKD trial.

In the new trial, EMPA-Kidney, treatment with empagliflozin 10 mg daily for a median of 2.0 years led to a significant 28% relative risk reduction in the primary combined endpoint in comparison with placebo, William G. Herrington, MD, reported at the annual meeting of the American Society of Nephrology.

The results were simultaneously published in the New England Journal of Medicine.

In 2020, a different team of researchers running DAPA-CKD reported that during a median of 2.4 years, treatment of 4,304 patients with dapagliflozin 10 mg daily resulted in a significant 39% relative risk reduction, compared with placebo for an identical combined primary endpoint. Enrollment criteria for the DAPA-CKD trial were mostly similar to that of the current trial.

‘Remarkably similar’ findings

Results from EMPA-Kidney and DAPA-CKD are “remarkably similar,” said Dr. Herrington during a press briefing at the meeting.

He also noted that when the EMPA-Kidney study began – before results from DAPA-CKD were known – “we never imagined such a large effect” on important endpoints in people with CKD.

In addition to cardiovascular death, the combined primary endpoint included the incidence of renal death, incident end-stage kidney disease, a sustained decrease in estimated glomerular filtration rate to less than 10 mL/min per 1.73m², or a sustained decrease in eGFR of at least 40% from baseline.

Having similar evidence from both trials “will hopefully provide people with the confidence to start to use SGLT2 inhibitors as standard care in people with CKD” who match enrollment criteria of the two trials, added Dr. Herrington, a nephrologist at the University of Oxford (England).

The analyses he reported also showed that empagliflozin had similar efficacy for the primary endpoint regardless of whether patients had type 2 diabetes at the time of enrollment and regardless of their eGFR at entry.

To enter EMPA-Kidney, people needed to have either an eGFR of 20-44 mL/min per 1.73m² with no minimum level of albuminuria or an eGFR of 45-89 mL/min per 1.73m² with a urine albumin-to-creatinine ratio (UACR) of at least 200 mg/g.

In contrast, to enroll in DAPA-CKD, patients had to have a UACR of at least 200 mg/g. This means that for the first time, EMPA-Kidney produced data on the relationship between albuminuria severity and the impact of treatment with an SGLT2 inhibitor in the enrolled population.

A signal of greater efficacy with higher UACR

A total of 6,609 patients underwent randomization in EMPA-Kidney. During a median of 2.0 years of follow-up, the primary endpoint – progression of kidney disease or death from cardiovascular causes – occurred in 432 of 3,304 patients (13.1%) in the empagliflozin group and in 558 of 3,305 patients (16.9%) in the placebo group (hazard ratio, 0.72; P < .001).

The results “suggested that the effects [of empagliflozin] are greater in patients with higher levels of albuminuria, with statistically significant heterogeneity between this subgroup and those with a UACR of less than 200 mg/g (P = .02),” Dr. Herrington said.

Of the study population, 54% had no evidence of diabetes at enrollment.

Having data from a second large trial of an SGLT2 inhibitor that included people with isolated CKD who did not have diabetes or heart failure “will start to move the needle” on using this class of drugs in these types of patients, commented F. Perry Wilson, MD, a nephrologist at Yale University, New Haven, Conn.

On the basis of the DAPA-CKD results, in April 2021 the Food and Drug Administration expanded dapagliflozin’s indications to include CKD, yet, “a lot of nephrologists consider SGLT2 inhibitors to be agents for people with diabetes or heart failure, and they defer prescribing them to endocrinologists and cardiologists,” Dr. Wilson said in an interview.

‘Flozinators’ rising

But Pascale H. Lane, MD, a pediatric nephrologist at the University of Oklahoma Health Sciences Center, Oklahoma City, commented that many nephrologists she knows have been prescribing dapagliflozin “widely” to their patients with CKD.

“I know many adult nephrologists who use it almost universally now,” Dr. Lane said. “They call themselves ‘flozinators.’ ”

EMPA-Kidney was sponsored by Boehringer Ingelheim, the company that along with Lilly markets empagliflozin (Jardiance). Dr. Herrington, Dr. Wilson, and Dr. Lane disclosed no relevant financial relationships.

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

Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

• In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
• Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
• Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
• Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
• Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
• Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
• Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
• For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

• In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
• Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
• Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
• Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
• Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
• Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
• Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
• For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

• In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
• Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
• Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
• Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
• Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
• Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
• Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
• For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

Bad drinking consequence No. 87: Joining the LOTME team

Alcohol and college students go together like peanut butter and jelly. Or peanut butter and chocolate. Or peanut butter and toothpaste. Peanut butter goes with a lot of things.

Naturally, when you combine alcohol and college students, bad decisions are sure to follow. But have you ever wondered just how many bad decisions alcohol causes? A team of researchers from Penn State University, the undisputed champion of poor drinking decisions (trust us, we know), sure has. They’ve even conducted a 4-year study of 1,700 students as they carved a drunken swath through the many fine local drinking establishments, such as East Halls or that one frat house that hosts medieval battle–style ping pong tournaments.

elevate/PxHere

The students were surveyed twice a year throughout the study, and the researchers compiled a list of all the various consequences their subjects experienced. Ultimately, college students will experience an average of 102 consequences from drinking during their 4-year college careers, which is an impressive number. Try thinking up a hundred consequences for anything.

Some consequences are less common than others – we imagine “missing the Renaissance Faire because you felt drunker the morning after than while you were drinking” is pretty low on the list – but more than 96% of students reported that they’d experienced a hangover and that drinking had caused them to say or do embarrassing things. Also, more than 70% said they needed additional alcohol to feel any effect, a potential sign of alcohol use disorder.

Once they had their list, the researchers focused on 12 of the more common and severe consequences, such as blacking out, hangovers, and missing work/class, and asked the study participants how their parents would react to their drinking and those specific consequences. Students who believed their parents would disapprove of alcohol-related consequences actually experienced fewer consequences overall.

College students, it seems, really do care what their parents think, even if they don’t express it, the researchers said. That gives space for parents to offer advice about the consequences of hard drinking, making decisions while drunk, or bringing godawful Fireball whiskey to parties. Seriously, don’t do that. Stuff’s bad, and you should feel bad for bringing it. Your parents raised you better than that.
 

COVID ‘expert’ discusses data sharing

We interrupt our regularly scheduled programming to bring you this special news event. Elon Musk, the world’s second-most annoying human, is holding a press conference to discuss, of all things, COVID-19.

Reporter: Hey, Mr. Musketeer, what qualifies you to talk about a global pandemic?

EM: As the official king of the Twitterverse, I’m pretty much an expert on any topic.

Reporter: Okay then, Mr. Muskmelon, what can you tell us about the new study in Agricultural Economics, which looked at consumers’ knowledge of local COVID infection rates and their willingness to eat at restaurants?

Dmitry Zvolskiy

That’s all the time I have to chat with you today. I’m off to fire some more Twitter employees.

In case you hadn’t already guessed, Vlad Putin is officially more annoying than Elon Musk. We now return to this week’s typical LOTME shenanigans, already in progress.
 

The deadliest month

With climate change making the world hotter, leading to more heat stroke and organ failure, you would think the summer months would be the most deadly. In reality, though, it’s quite the opposite.

Nothing Ahead

There are multiple factors that make January the most deadly month out of the year, as LiveScience discovered in a recent analysis.

Let’s go through them, shall we?

Respiratory viruses: Robert Glatter, MD, of Lenox Hill Hospital in New York, told LiveScence that winter is the time for illnesses like the flu, bacterial pneumonia, and RSV. Millions of people worldwide die from the flu, according to the CDC. And the World Health Organization reported lower respiratory infections as the fourth-leading cause of death worldwide before COVID came along.

Heart disease: Heart conditions are actually more fatal in the winter months, according to a study published in Circulation. The cold puts more stress on the heart to keep the body warm, which can be a challenge for people who already have preexisting heart conditions.

Space heaters: Dr. Glatter also told Live Science that the use of space heaters could be a factor in the cold winter months since they can lead to carbon monoxide poisoning and even fires. Silent killers.

Holiday season: A time for joy and merriment, certainly, but Christmas et al. have their downsides. By January we’re coming off a 3-month food and alcohol binge, which leads to cardiac stress. There’s also the psychological stress that comes with the season. Sometimes the most wonderful time of the year just isn’t.

So even though summer is hot, fall has hurricanes, and spring tends to have the highest suicide rate, winter still ends up being the deadliest season.