Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.

Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.

“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.

The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.


The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).

For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.

“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”

The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.

This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.

SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.

Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.

Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.

“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.

The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.


The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).

For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.

“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”

The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.

This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.

SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.

Patients with rheumatoid arthritis using tumor necrosis factor inhibitors do not appear to have a lower rate of joint replacement when compared with patients taking conventional synthetic disease-modifying antirheumatic drugs, according to an analysis of data in the British Society for Rheumatology Biologics Register for RA.

Although there was not a general protective effect, patients with rheumatoid arthritis (RA) who were 60 years or older had a 40% reduction in total hip replacement (THR) when using tumor necrosis factor inhibitors (TNFi), according to first author Samuel Hawley from the Nuffield Department of Orthopaedics in the Rheumatology and Musculoskeletal Sciences at the University of Oxford (England) and his colleagues.

“While a reduction in THR amongst older TNFi users offers some support for biologics playing a role in reducing need for joint replacement, it must also be noted that the lack of an overall protective effect is suggestive that other factors apart from TNFi are likely to be involved in the ... downward population trends in joint replacement rates in RA,” Mr. Hawley and his colleagues wrote in their report published in the journal Rheumatology.

The researchers analyzed prospectively collected data on 11,202 RA patients from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) from 2001-2016 who were using TNFi (n = 9,558) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; n = 1,644). Patients had a median disease duration of 11.0 years in the TNFi group and 10.8 years in the csDMARD group. TNFi and csDMARD users were matched based on their propensity to receive treatment, and researchers used a Cox regression analysis to compare the rates of total knee replacement (TKR), THR, and other joint replacement. The researchers utilized each csDMARD user a median of three times (interquartile range, one to six) in the comparisons.


The incidence rate for THR was 5.22/1,000 person-years for TNFi users and 6.30/1,000 person-years for csDMARD users, while the incidence rate for TKR was 8.89/1,000 person-years for TNFi users and 8.09/1,000 person-years for csDMARD users. Mr. Hawley and his colleagues found no association between TNFi use and THR when compared with csDMARD users (adjusted pooled hazard ratio, 0.86; 95% confidence interval, 0.60-1.22; P = .39) based on 589 THRs during follow-up. There was also no association between the incidence of TKR and TNFi use when compared with csDMARD users (adjusted pooled HR, 1.11; 95% CI, 0.84-1.47; P = .46) based on 846 TKRs during follow-up. When the researchers examined 336 other joint replacements performed during follow-up, there was also no significant difference in incidence between TNFi and csDMARD users (HR, 1.15; 95% CI, 0.75-1.77).

For patients 60 years or older, TNFi use was associated with a 40% reduction in THR incidence (HR, 0.60; 95% CI, 0.41-0.87; P = .008), but not in TKR incidence. However, younger patients using TNFi did not have a reduced incidence of THR, and there were no associations between TNFi use and incidence of TKR or other joint replacements.

“It could be that the relatively long disease duration at our baseline meant there was greater potential for prevention of joint destruction at the hip over knee, although details of differential natural history of RA disease at these two joints are not well established,” the researchers wrote. “It is also very difficult to disentangle the impact of TNFi on improved function and overall quality of life and how this may have mediated effects on longer-term progression of joint damage, potentially differentially at the knee and hip.”

The researchers said the study was limited by the potential for residual confounding by indication, and the long disease duration of patients means that the results would not be generalizable to patients with early RA. In addition, underreporting of joint replacement could create bias because the registry information is a combination of physician-reported and self-reported incidences, they added.

This study was funded by an award from the National Institute for Health Research (NIHR) and support from the Oxford NIHR Biomedical Research Unit. Four authors disclosed financial relationships with industry, including many companies marketing biologics for RA. Other authors reported no relevant conflicts of interest.

SOURCE: Hawley S et al. Rheumatology. 2019 Jan 10. doi: 10.1093/rheumatology/key424.

Ultraviolet radiation (UVR) exposure was found to extensively alter the composition of the cutaneous microbial composition in healthy young men, in a small pilot study published in Experimental Dermatology.

“Human skin and its microbial inhabitants are also subject to the effects of external and environmental stressors, such as ultraviolet radiation,” wrote Erin M. Burns, MS, PhD, of the department of dermatology at the University of Alabama at Birmingham, and her coauthors. “Environmental factors specific to the individual may modulate colonization of skin microbiota, and knowledge of how they do so can advance our understanding of the delicate balance between host and microorganisms,” they added.

In the study, the researchers conducted a prospective analysis of six males with Fitzpatrick types I or II skin exposed to various sources of UVR, including UVA1 and narrowband UVB. Participants received differing doses of irradiation, which was applied to the left upper or mid-back.

Both pre- and postexposure skin samples were obtained directly and 24 hours following UVR exposure. DNA from the cutaneous swabs was isolated and replicated via sequencing technology, which was used to analyze the microbial makeup of each sample.

After genomic analysis, Dr. Burns and her colleagues found extensive microbial differences among participants at each data collection point. Bacterial composition of the skin biome was altered 24 hours post UVR exposure both within and between study subjects, which included species- and phylum-level changes. While changes varied widely, trends that they identified included a “general increase” in the phylum Cyanobacteria and decreases in the family Lactobacillaceae and Pseudomonadaceae, they wrote.

Two key limitations of the study were the small sample size and inclusion of male participants only, which limits the generalizability of the results, the authors noted.

“These findings could add new insight into the treatment of UV-induced cutaneous inflammation and other skin diseases linked to microbiome shifts or UVR exposure,” they concluded. Future studies, they added, could address “the question of a protective nature of microbial inhabitants of the healthy skin microbiome,” which “may pave the way for the use of prophylactic probiotics for dermatologic health management.”

This study was supported by grant funding from the National Institutes of Health and University of Alabama at Birmingham. The authors – from the University of Alabama as well as Henry Ford Hospital, Detroit, and Florida State University, Tallahassee – reported no conflicts of interest.

SOURCE: Burns EM et al. Exp Dermatol. 2018 Dec 02. doi: 10.1111/exd.13854.

Ultraviolet radiation (UVR) exposure was found to extensively alter the composition of the cutaneous microbial composition in healthy young men, in a small pilot study published in Experimental Dermatology.

“Human skin and its microbial inhabitants are also subject to the effects of external and environmental stressors, such as ultraviolet radiation,” wrote Erin M. Burns, MS, PhD, of the department of dermatology at the University of Alabama at Birmingham, and her coauthors. “Environmental factors specific to the individual may modulate colonization of skin microbiota, and knowledge of how they do so can advance our understanding of the delicate balance between host and microorganisms,” they added.

In the study, the researchers conducted a prospective analysis of six males with Fitzpatrick types I or II skin exposed to various sources of UVR, including UVA1 and narrowband UVB. Participants received differing doses of irradiation, which was applied to the left upper or mid-back.

Both pre- and postexposure skin samples were obtained directly and 24 hours following UVR exposure. DNA from the cutaneous swabs was isolated and replicated via sequencing technology, which was used to analyze the microbial makeup of each sample.

After genomic analysis, Dr. Burns and her colleagues found extensive microbial differences among participants at each data collection point. Bacterial composition of the skin biome was altered 24 hours post UVR exposure both within and between study subjects, which included species- and phylum-level changes. While changes varied widely, trends that they identified included a “general increase” in the phylum Cyanobacteria and decreases in the family Lactobacillaceae and Pseudomonadaceae, they wrote.

Two key limitations of the study were the small sample size and inclusion of male participants only, which limits the generalizability of the results, the authors noted.

“These findings could add new insight into the treatment of UV-induced cutaneous inflammation and other skin diseases linked to microbiome shifts or UVR exposure,” they concluded. Future studies, they added, could address “the question of a protective nature of microbial inhabitants of the healthy skin microbiome,” which “may pave the way for the use of prophylactic probiotics for dermatologic health management.”

This study was supported by grant funding from the National Institutes of Health and University of Alabama at Birmingham. The authors – from the University of Alabama as well as Henry Ford Hospital, Detroit, and Florida State University, Tallahassee – reported no conflicts of interest.

SOURCE: Burns EM et al. Exp Dermatol. 2018 Dec 02. doi: 10.1111/exd.13854.

Ultraviolet radiation (UVR) exposure was found to extensively alter the composition of the cutaneous microbial composition in healthy young men, in a small pilot study published in Experimental Dermatology.

“Human skin and its microbial inhabitants are also subject to the effects of external and environmental stressors, such as ultraviolet radiation,” wrote Erin M. Burns, MS, PhD, of the department of dermatology at the University of Alabama at Birmingham, and her coauthors. “Environmental factors specific to the individual may modulate colonization of skin microbiota, and knowledge of how they do so can advance our understanding of the delicate balance between host and microorganisms,” they added.

In the study, the researchers conducted a prospective analysis of six males with Fitzpatrick types I or II skin exposed to various sources of UVR, including UVA1 and narrowband UVB. Participants received differing doses of irradiation, which was applied to the left upper or mid-back.

Both pre- and postexposure skin samples were obtained directly and 24 hours following UVR exposure. DNA from the cutaneous swabs was isolated and replicated via sequencing technology, which was used to analyze the microbial makeup of each sample.

After genomic analysis, Dr. Burns and her colleagues found extensive microbial differences among participants at each data collection point. Bacterial composition of the skin biome was altered 24 hours post UVR exposure both within and between study subjects, which included species- and phylum-level changes. While changes varied widely, trends that they identified included a “general increase” in the phylum Cyanobacteria and decreases in the family Lactobacillaceae and Pseudomonadaceae, they wrote.

Two key limitations of the study were the small sample size and inclusion of male participants only, which limits the generalizability of the results, the authors noted.

“These findings could add new insight into the treatment of UV-induced cutaneous inflammation and other skin diseases linked to microbiome shifts or UVR exposure,” they concluded. Future studies, they added, could address “the question of a protective nature of microbial inhabitants of the healthy skin microbiome,” which “may pave the way for the use of prophylactic probiotics for dermatologic health management.”

This study was supported by grant funding from the National Institutes of Health and University of Alabama at Birmingham. The authors – from the University of Alabama as well as Henry Ford Hospital, Detroit, and Florida State University, Tallahassee – reported no conflicts of interest.

SOURCE: Burns EM et al. Exp Dermatol. 2018 Dec 02. doi: 10.1111/exd.13854.

Patient-specific half maximal factor VIII effective concentrations measured using thromboelastography may be an accurate biomarker to predict efficacy of prophylaxis in severe hemophilia A.

Ihosvany Fernández-Bello, PhD, of La Paz University Hospital in Spain, along with his colleagues, used thromboelastography to investigate the pharmacodynamics of FVIII in young patients with severe hemophilia A who were under a long-term-prophylactic regimen. The findings of the observational, cross-sectional study were published in the European Journal of Pharmaceutical Sciences.

The researchers followed 19 patients under 18 years of age with severe hemophilia A receiving prophylactic treatment. They analyzed their joint condition, bleeding phenotype, and physical activity, compared with their individual pharmacodynamic/pharmacokinetic parameters of FVIII.

They analyzed whole blood withdrawn before FVIII administration and at five time points after treatment. Treated spontaneous bleeding events in the previous 2 years were retrospectively assessed.

Dr. Fernández-Bello and his colleagues measured half maximal factor VIII effective concentrations using thromboelastography, which was correlated with variables related to individual bleeding phenotype.

After analysis, only half maximal FVIII effective concentration of FVIII for thromboelastography parameters R-time, K-time, and alpha-angle were correlated with the bleeding phenotype. Other parameters, including joint condition, type of prophylaxis regimen, and FVIII trough concentrations were not predictive of bleeding phenotype.

“Our results are encouraging and offer the added value of having been obtained in a particularly fragile population considered particularly difficult to study,” they wrote.

The authors noted two key limitations were the small sample size and retrospective nature of the study. Despite the low number of participants, statistical significance of key bleeding outcomes were still achieved.

“This study reveals [half maximal effective concentration of FVIII] for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in [severe hemophilia A],” they concluded.

The study was supported by grant funding from Novo Nordisk, the World Federation of Hemophilia, and the Spanish Society of Thrombosis and Hemostasis. The authors’ financial affiliations were not reported.

SOURCE: Fernández-Bello I et al. Eur J Pharm Sci. 2019 Feb 1;128:215-21.

Patient-specific half maximal factor VIII effective concentrations measured using thromboelastography may be an accurate biomarker to predict efficacy of prophylaxis in severe hemophilia A.

Ihosvany Fernández-Bello, PhD, of La Paz University Hospital in Spain, along with his colleagues, used thromboelastography to investigate the pharmacodynamics of FVIII in young patients with severe hemophilia A who were under a long-term-prophylactic regimen. The findings of the observational, cross-sectional study were published in the European Journal of Pharmaceutical Sciences.

The researchers followed 19 patients under 18 years of age with severe hemophilia A receiving prophylactic treatment. They analyzed their joint condition, bleeding phenotype, and physical activity, compared with their individual pharmacodynamic/pharmacokinetic parameters of FVIII.

They analyzed whole blood withdrawn before FVIII administration and at five time points after treatment. Treated spontaneous bleeding events in the previous 2 years were retrospectively assessed.

Dr. Fernández-Bello and his colleagues measured half maximal factor VIII effective concentrations using thromboelastography, which was correlated with variables related to individual bleeding phenotype.

After analysis, only half maximal FVIII effective concentration of FVIII for thromboelastography parameters R-time, K-time, and alpha-angle were correlated with the bleeding phenotype. Other parameters, including joint condition, type of prophylaxis regimen, and FVIII trough concentrations were not predictive of bleeding phenotype.

“Our results are encouraging and offer the added value of having been obtained in a particularly fragile population considered particularly difficult to study,” they wrote.

The authors noted two key limitations were the small sample size and retrospective nature of the study. Despite the low number of participants, statistical significance of key bleeding outcomes were still achieved.

“This study reveals [half maximal effective concentration of FVIII] for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in [severe hemophilia A],” they concluded.

The study was supported by grant funding from Novo Nordisk, the World Federation of Hemophilia, and the Spanish Society of Thrombosis and Hemostasis. The authors’ financial affiliations were not reported.

SOURCE: Fernández-Bello I et al. Eur J Pharm Sci. 2019 Feb 1;128:215-21.

Patient-specific half maximal factor VIII effective concentrations measured using thromboelastography may be an accurate biomarker to predict efficacy of prophylaxis in severe hemophilia A.

Ihosvany Fernández-Bello, PhD, of La Paz University Hospital in Spain, along with his colleagues, used thromboelastography to investigate the pharmacodynamics of FVIII in young patients with severe hemophilia A who were under a long-term-prophylactic regimen. The findings of the observational, cross-sectional study were published in the European Journal of Pharmaceutical Sciences.

The researchers followed 19 patients under 18 years of age with severe hemophilia A receiving prophylactic treatment. They analyzed their joint condition, bleeding phenotype, and physical activity, compared with their individual pharmacodynamic/pharmacokinetic parameters of FVIII.

They analyzed whole blood withdrawn before FVIII administration and at five time points after treatment. Treated spontaneous bleeding events in the previous 2 years were retrospectively assessed.

Dr. Fernández-Bello and his colleagues measured half maximal factor VIII effective concentrations using thromboelastography, which was correlated with variables related to individual bleeding phenotype.

After analysis, only half maximal FVIII effective concentration of FVIII for thromboelastography parameters R-time, K-time, and alpha-angle were correlated with the bleeding phenotype. Other parameters, including joint condition, type of prophylaxis regimen, and FVIII trough concentrations were not predictive of bleeding phenotype.

“Our results are encouraging and offer the added value of having been obtained in a particularly fragile population considered particularly difficult to study,” they wrote.

The authors noted two key limitations were the small sample size and retrospective nature of the study. Despite the low number of participants, statistical significance of key bleeding outcomes were still achieved.

“This study reveals [half maximal effective concentration of FVIII] for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in [severe hemophilia A],” they concluded.

The study was supported by grant funding from Novo Nordisk, the World Federation of Hemophilia, and the Spanish Society of Thrombosis and Hemostasis. The authors’ financial affiliations were not reported.

SOURCE: Fernández-Bello I et al. Eur J Pharm Sci. 2019 Feb 1;128:215-21.

As reported in the Wall Street Journal, the current administration has proposed a suite of initiatives that could improve patients’ access to their health data, including doctors’ and hospitals’ electronic records as well as insurance claim information (“Rules to Ease Patient Access to Health Data Are Proposed,” by Anna Wilde Mathews, Feb. 11, 2019). One of the draft rules would mandate new technology standards that allow health information data to flow seamlessly between providers and hospitals using different electronic systems, a step that should have been taken well before the federal government began cajoling physicians into adopting not-ready-for-prime-time EMR systems and rewarding their “meaningful use.” Other rules are aimed at discouraging the patient-unfriendly practice of delaying and charging for the transfer of medical records.

pandpstock001/ThinkStock.com

Apple already has begun research and development on systems and tools that would allow patients to receive and store their health information on their smart phones and tablets. Arriving at the ED or a consulting physician, the patient would need only unlock his or her device to share his or her medical record.

These proposals are long overdue and in the long run should save providers and patients time and expense. As long as they also include rules mandating true transparency in hospital billing, these initiatives appear to be heading us in the right direction.

Are you prepared to deal with transparency when it comes to your medical records? Do you create your office notes with the assumption that your patient will be reading them? Seventy-five years ago, physicians, many of whom were in solo practice, scrawled their notes as simple mnemonics. They could barely decipher their own scribbles. If they needed to share information with a consultant, it was with a phone call or dictated letter. You probably are more aware of creating a readable note because you rely on covering physicians ... and you know that the folks who pay you will be auditing your charts.

Depending on your patient mix, most of the notes you generate probably don’t contain many observations that you are hesitant to share with the patient. If you haven’t already discussed his body mass index with the patient you have described as “obese,” you aren’t doing your job. However, occasionally there are topics that have arisen in the family and social history that may not be pertinent to the patient’s current problem, but provide a more nuanced picture of her and serve as a mnemonic at a later visit. Will the patient mind if you include these tidbits in an electronic record that may be shared by a wide audience outside the confines of your exam room?

How do you deal with situations like this when the threat of transparency could interfere with our relationship with our patients? You could ask the patient, “ Do you mind if I include that event you just told me, in your EMR?” You could create a “shadow record” that includes information the patient prefers not to be shared and your own observations that you don’t feel comfortable sharing with the patient. Is this “shadow record” something electronic that could be redacted by simply toggling a clickable box? Or is it an old-fashioned paper note you keep in a separate file in a locked drawer in a file cabinet (if you even have a file cabinet)? I fear the lawyers would have something to say about both those options. The best solution may simply be to rely on your memory. If you have so many patients that you can’t remember those occasional sensitive issues that have been shared with you, then maybe you have too many patients.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

As reported in the Wall Street Journal, the current administration has proposed a suite of initiatives that could improve patients’ access to their health data, including doctors’ and hospitals’ electronic records as well as insurance claim information (“Rules to Ease Patient Access to Health Data Are Proposed,” by Anna Wilde Mathews, Feb. 11, 2019). One of the draft rules would mandate new technology standards that allow health information data to flow seamlessly between providers and hospitals using different electronic systems, a step that should have been taken well before the federal government began cajoling physicians into adopting not-ready-for-prime-time EMR systems and rewarding their “meaningful use.” Other rules are aimed at discouraging the patient-unfriendly practice of delaying and charging for the transfer of medical records.

pandpstock001/ThinkStock.com

Apple already has begun research and development on systems and tools that would allow patients to receive and store their health information on their smart phones and tablets. Arriving at the ED or a consulting physician, the patient would need only unlock his or her device to share his or her medical record.

These proposals are long overdue and in the long run should save providers and patients time and expense. As long as they also include rules mandating true transparency in hospital billing, these initiatives appear to be heading us in the right direction.

Are you prepared to deal with transparency when it comes to your medical records? Do you create your office notes with the assumption that your patient will be reading them? Seventy-five years ago, physicians, many of whom were in solo practice, scrawled their notes as simple mnemonics. They could barely decipher their own scribbles. If they needed to share information with a consultant, it was with a phone call or dictated letter. You probably are more aware of creating a readable note because you rely on covering physicians ... and you know that the folks who pay you will be auditing your charts.

Depending on your patient mix, most of the notes you generate probably don’t contain many observations that you are hesitant to share with the patient. If you haven’t already discussed his body mass index with the patient you have described as “obese,” you aren’t doing your job. However, occasionally there are topics that have arisen in the family and social history that may not be pertinent to the patient’s current problem, but provide a more nuanced picture of her and serve as a mnemonic at a later visit. Will the patient mind if you include these tidbits in an electronic record that may be shared by a wide audience outside the confines of your exam room?

How do you deal with situations like this when the threat of transparency could interfere with our relationship with our patients? You could ask the patient, “ Do you mind if I include that event you just told me, in your EMR?” You could create a “shadow record” that includes information the patient prefers not to be shared and your own observations that you don’t feel comfortable sharing with the patient. Is this “shadow record” something electronic that could be redacted by simply toggling a clickable box? Or is it an old-fashioned paper note you keep in a separate file in a locked drawer in a file cabinet (if you even have a file cabinet)? I fear the lawyers would have something to say about both those options. The best solution may simply be to rely on your memory. If you have so many patients that you can’t remember those occasional sensitive issues that have been shared with you, then maybe you have too many patients.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

As reported in the Wall Street Journal, the current administration has proposed a suite of initiatives that could improve patients’ access to their health data, including doctors’ and hospitals’ electronic records as well as insurance claim information (“Rules to Ease Patient Access to Health Data Are Proposed,” by Anna Wilde Mathews, Feb. 11, 2019). One of the draft rules would mandate new technology standards that allow health information data to flow seamlessly between providers and hospitals using different electronic systems, a step that should have been taken well before the federal government began cajoling physicians into adopting not-ready-for-prime-time EMR systems and rewarding their “meaningful use.” Other rules are aimed at discouraging the patient-unfriendly practice of delaying and charging for the transfer of medical records.

pandpstock001/ThinkStock.com

Apple already has begun research and development on systems and tools that would allow patients to receive and store their health information on their smart phones and tablets. Arriving at the ED or a consulting physician, the patient would need only unlock his or her device to share his or her medical record.

These proposals are long overdue and in the long run should save providers and patients time and expense. As long as they also include rules mandating true transparency in hospital billing, these initiatives appear to be heading us in the right direction.

Are you prepared to deal with transparency when it comes to your medical records? Do you create your office notes with the assumption that your patient will be reading them? Seventy-five years ago, physicians, many of whom were in solo practice, scrawled their notes as simple mnemonics. They could barely decipher their own scribbles. If they needed to share information with a consultant, it was with a phone call or dictated letter. You probably are more aware of creating a readable note because you rely on covering physicians ... and you know that the folks who pay you will be auditing your charts.

Depending on your patient mix, most of the notes you generate probably don’t contain many observations that you are hesitant to share with the patient. If you haven’t already discussed his body mass index with the patient you have described as “obese,” you aren’t doing your job. However, occasionally there are topics that have arisen in the family and social history that may not be pertinent to the patient’s current problem, but provide a more nuanced picture of her and serve as a mnemonic at a later visit. Will the patient mind if you include these tidbits in an electronic record that may be shared by a wide audience outside the confines of your exam room?

How do you deal with situations like this when the threat of transparency could interfere with our relationship with our patients? You could ask the patient, “ Do you mind if I include that event you just told me, in your EMR?” You could create a “shadow record” that includes information the patient prefers not to be shared and your own observations that you don’t feel comfortable sharing with the patient. Is this “shadow record” something electronic that could be redacted by simply toggling a clickable box? Or is it an old-fashioned paper note you keep in a separate file in a locked drawer in a file cabinet (if you even have a file cabinet)? I fear the lawyers would have something to say about both those options. The best solution may simply be to rely on your memory. If you have so many patients that you can’t remember those occasional sensitive issues that have been shared with you, then maybe you have too many patients.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

This week in MDedge Cardiocast: Most tPA-eligible stroke patients now get treated within an hour, atrial fib patients with prior hemorrhagic stroke who get their LAA closed can be safely treated, SGLT2 inhibitors are quickly morphing from diabetes to heart failure drugs, and the MESA cardiovascular disease risk calculator can be an improvement on the ACC/AHA version.

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This week in MDedge Cardiocast: Most tPA-eligible stroke patients now get treated within an hour, atrial fib patients with prior hemorrhagic stroke who get their LAA closed can be safely treated, SGLT2 inhibitors are quickly morphing from diabetes to heart failure drugs, and the MESA cardiovascular disease risk calculator can be an improvement on the ACC/AHA version.

Amazon AlexaApple Podcasts

Google Podcasts

TuneIn

This week in MDedge Cardiocast: Most tPA-eligible stroke patients now get treated within an hour, atrial fib patients with prior hemorrhagic stroke who get their LAA closed can be safely treated, SGLT2 inhibitors are quickly morphing from diabetes to heart failure drugs, and the MESA cardiovascular disease risk calculator can be an improvement on the ACC/AHA version.

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Google Podcasts

TuneIn

Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.

snyferok/Thinkstock

“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.

Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.

“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.


 

The role of diet

Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.

They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.

The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
 

Potential confounding

“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.

While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.

In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.

“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.

It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.

These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
 

Adding insights

The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).

“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.

The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.

[email protected]

SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.

Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.

snyferok/Thinkstock

“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.

Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.

“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.


 

The role of diet

Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.

They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.

The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
 

Potential confounding

“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.

While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.

In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.

“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.

It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.

These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
 

Adding insights

The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).

“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.

The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.

[email protected]

SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.

Among older adults, adherence to a Mediterranean diet is associated with lower probability of prodromal Parkinson’s disease, according to research published in Movement Disorders.

snyferok/Thinkstock

“Recommending the Mediterranean diet pattern, either to reduce the risk or lessen the effects ... of prodromal Parkinson’s disease, needs to be considered and further explored,” said lead author Maria I. Maraki, PhD, of the department of nutrition and dietetics at Harokopio University in Athens, Greece, and her research colleagues.

Evidence regarding the effect of a Mediterranean diet on Parkinson’s disease risk remains limited, however, and physicians should be cautious in interpreting the data, researchers noted in accompanying editorials.

“There is a puzzling constellation of information and data that cannot be reconciled with a simple model accounting for the role of diet, vascular risk factors, and the neurodegenerative process and mechanisms underlying Parkinson’s disease,” Connie Marras, MD, PhD, and Jose A. Obeso, MD, PhD, said in an editorial. Given Maraki et al.’s findings, “most of us would be glad to accept that such a causal inverse association exists and can therefore be strongly recommended to our patients,” but “further work is needed before definitive conclusions can be reached,” Dr. Marras and Dr. Obeso wrote. Dr. Marras is affiliated with the University Health Network and the University of Toronto. Dr. Obeso is affiliated with University Hospital HM Puerta del Sur, CEU San Pablo University, Móstoles, Spain.


 

The role of diet

Prior research has suggested that adherence to the Mediterranean diet – characterized by consumption of nonrefined cereals, fruits, vegetables, legumes, potatoes, fish, and olive oil – may be associated with reduced risk of Parkinson’s disease. In addition, studies have found that adherence to the Mediterranean diet may be protective in other diseases, including dementia and cardiovascular disease. Dr. Maraki and her colleagues sought to assess whether adherence to the Mediterranean diet is associated with the likelihood of prodromal Parkinson’s disease or its manifestations. To calculate the probability of prodromal Parkinson’s disease, the investigators used a tool created by the International Parkinson and Movement Disorder Society (MDS) that takes into account baseline risk factors as well as prodromal markers such as constipation and motor slowing.

They analyzed data from 1,731 participants in the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort in Greece. Participants, 41% of whom were male, were aged 65 years or older and did not have Parkinson’s disease. They completed a detailed food frequency questionnaire, and the researchers calculated how closely each participant’s diet adhered to the Mediterranean diet. Diet adherence scores ranged from 0 to 55, with higher scores indicating greater adherence.

The median probability of prodromal Parkinson’s disease was 1.9% (range, 0.2%-96.7%), and the probability was lower among those with greater adherence to the Mediterranean diet. This difference was “driven mostly by nonmotor markers of prodromal Parkinson’s disease,” including depression, constipation, urinary dysfunction, and daytime somnolence, the researchers said. “Each unit increase in Mediterranean diet score was associated with a 2% decreased probability for prodromal Parkinson’s disease.” Compared with participants in the lowest quartile of Mediterranean diet adherence, those in the highest quartile had an approximately 21% lower probability for prodromal Parkinson’s disease.
 

Potential confounding

“This study pushes the prodromal criteria into performing a job they were never designed to do,” which presents potential pitfalls, Ronald B. Postuma, MD, of the department of neurology at Montreal General Hospital in Quebec, said in an accompanying editorial.

While the MDS criteria were designed to assess the likelihood that any person over age 50 years is in a state of prodromal Parkinson’s disease, the present study aimed to evaluate whether a single putative risk factor for Parkinson’s disease is associated with the likelihood of its prodromal state.

In addition, the analysis did not include some of the prodromal markers that are part of the MDS criteria, including olfaction, polysomnographic-proven REM sleep behavior disorder, and dopaminergic functional neuroimaging.

“As pointed out by the researchers, many of the risk factors in the prodromal criteria are potentially confounded by factors other than Parkinson’s disease; for example, one could imagine that older people, men, or farmers (with their higher pesticide exposure) are less likely to follow the Mediterranean diet simply because of different cultural lifestyle patterns,” Dr. Postuma said.

It is also possible that the Mediterranean diet affects prodromal markers such as constipation, sleep, or depression without affecting underlying neurodegenerative disease. In any case, the effect sizes observed in the study were small, and there was no evidence that participants who adhered most closely to a Mediterranean diet had less parkinsonism, Dr. Postuma said.

These limitations do not preclude physicians from recommending the diet for other reasons. “Numerous studies, reviews, meta-analyses, and randomized controlled trials consistently rank the Mediterranean diet as among the healthiest diets available,” Dr. Postuma said. “So, one can clearly recommend diets such as these, even if not necessarily for Parkinson’s disease prevention.”
 

Adding insights

The researchers used a Mediterranean diet score that was developed in a population of adults from metropolitan Athens, “an area not unlike the one in which the score is being applied in the HELIAD study,” Christy C. Tangney, PhD, professor of clinical nutrition and preventive medicine and associate dean for research at Rush University Medical Center, Chicago, said in a separate editorial. As expected, the average Mediterranean diet adherence score in this study was higher than that in the Chicago Health and Aging Project (33.2 vs. 28.2).

“If we can identify differences in diet or lifestyle patterns and risk of this latent phase of Parkinson’s disease neurodegeneration, we may be one step closer to identifying preventive measures,” she said. Follow-up reports from HELIAD and other cohorts may allow researchers to assess how changes in dietary patterns relate to changes in Parkinson’s disease markers, the probability of prodromal Parkinson’s disease, and incident Parkinson’s disease, Dr. Tangney said.

The study authors had no conflicts of interest or financial disclosures. The study was supported by a grant from the Alzheimer’s Association, an ESPA‐EU grant cofunded by the European Social Fund and Greek National resources, and a grant from the Ministry for Health and Social Solidarity (Greece). Dr. Maraki and a coauthor have received financial support from the Greek State Scholarships Foundation. Dr. Tangney and Dr. Postuma had no conflicts of interest.

[email protected]

SOURCE: Maraki MI et al. Mov Disord. 2018 Oct 10. doi: 10.1002/mds.27489.

HONOLULU – Deferoxamine mesylate does not significantly improve 90-day outcomes after intracranial hemorrhage (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.

Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.

Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.

Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.

The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.

Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.

Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.

The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.

Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.

The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.

“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”

The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.

[email protected]

SOURCE: Selim MH et al. ISC 2019, Abstract LB22.

HONOLULU – Deferoxamine mesylate does not significantly improve 90-day outcomes after intracranial hemorrhage (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.

Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.

Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.

Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.

The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.

Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.

Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.

The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.

Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.

The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.

“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”

The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.

[email protected]

SOURCE: Selim MH et al. ISC 2019, Abstract LB22.

HONOLULU – Deferoxamine mesylate does not significantly improve 90-day outcomes after intracranial hemorrhage (ICH), according to trial results described at the International Stroke Conference sponsored by the American Heart Association. However, the drug is safe and well tolerated and data suggest that it may improve outcomes at 180 days.

Animal studies indicate that iron, which is released from hemolyzed red blood cells, accumulates in the brain after ICH and is associated with secondary neuronal injury and death. Researchers have found that deferoxamine, an iron chelator, provides neuroprotection and improves recovery after experimental ICH. The drug also has anti-inflammatory, antiapoptotic, and BP-lowering effects. Deferoxamine has been approved since the 1960s.

Magdy H. Selim, MD, PhD, a neurologist at Beth Israel Deaconess Medical Center in Boston, and colleagues hypothesized that treatment with deferoxamine could improve outcomes in patients with ICH. The researchers conducted a phase 2 clinical trial to evaluate whether deferoxamine should be studied in a phase 3 efficacy trial. In their multicenter, double-blind study, Dr. Selim and his colleagues randomized patients with spontaneous supratentorial ICH in equal groups to 32 mg/kg per day of deferoxamine or saline placebo. Treatments were administered as intravenous infusions for 3 consecutive days, and therapy was initiated within 24 hours after ICH onset. The follow-up period was 6 months.

Eligible participants had an National Institutes of Health Stroke Scale score of 6 or higher, a Glasgow Coma Scale score greater than 6, and had been functionally independent before the hemorrhage. The researchers excluded patients with a secondary cause for ICH or coagulopathy.

The primary endpoint in the futility analysis was the proportion of participants with a good clinical outcome – defined as a modified Rankin Scale (mRS) score of 0-2 – at 90 days and 180 days. The secondary endpoint was good outcome, defined as an mRS score of 0-3, at 90 days. Safety endpoints included all deferoxamine-related adverse events until day 7 or discharge (whichever was earlier) and serious adverse events through day 90.

Dr. Selim and his colleagues enrolled 294 participants in their trial, 3 of whom did not receive treatment. Of these included participants, 147 (50.5%) were randomized to placebo and 144 (49.5%) were randomized to deferoxamine. Participants’ mean age was 60.3 years, and 38.5% of the population was female.

Overall, the two study arms did not differ significantly according to demographic and clinical characteristics, however, there were more nonwhite patients in the deferoxamine arm than in the placebo arm, however. In addition, thalamic hemorrhage and intraventricular hemorrhage were more common in the placebo-treated group and hemorrhages in the putamen and basal ganglia were more common in the deferoxamine-treated group.

The rates of adverse events were comparable between the two study arms. Dr. Selim and his colleagues found no unexpected safety issues. Mortality was low, and the 90-day and 180-day mortality rates were comparable between the two treatment arms.

Approximately 34% of deferoxamine-treated patients and 33% of placebo-treated patients had an mRS score of 0-2 at 90 days. The adjusted absolute risk difference between arms was 0.6%; this result did not surpass the predefined futility threshold. The risk difference between groups for mRS score of 0-2 at 180 days was 8.6% in favor of deferoxamine, which did surpass the futility threshold.

The risk difference for meeting the secondary endpoint was 6.2% in favor of deferoxamine; this result did not surpass the futility threshold. Patients in both treatment groups improved between day 90 and day 180. The likelihood of good outcome was approximately 10% higher in the deferoxamine group at day 90 and 26% higher in the deferoxamine group at day 180.

“It is futile to conduct a phase 3 trial with the anticipation that treatment with deferoxamine would improve outcome, defined as mRS score of 0-2 at 90 days,” said Dr. Selim. “These data, together with the data from MISTIE and CLEAR, suggest that ICH trials need to have a longer follow-up period to capture the full extent of recovery after ICH. Several of our secondary analyses tended to favor deferoxamine over the placebo arm and leave open the possibility that deferoxamine might lead to improved outcome at 180 days.”

The researchers received support from the NIH and the National Institute of Neurological Disorders and Stroke.

[email protected]

SOURCE: Selim MH et al. ISC 2019, Abstract LB22.

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

In this episode, David Henry, MD, welcomes Daniel G. Haller, MD, to rehash research from ESMO 2018 as well as the way the meeting itself was run.

And Ilana Yurkiewicz, MD, stops by for this week’s Clinical Correlation. Dr. Yurkiewicz is a hematology fellow at Stanford and also is a columnist at MDedge Hematology/Oncology. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

SHOW NOTES

By Emily Bryer, DO
Resident in the department of internal medicine, University of Pennsylvania Health System

• CheckMate 142: Durable clinical benefit with nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite high (MSI-H) and non-MSI-H colon cancer
  • Phase 2 study included 45 patients with metastatic colorectal cancer
  • Overall response rate (primary end point) was 60% and disease control rate was 84%
  • Almost every patient had some response and the therapy was well-tolerated
  • https://academic.oup.com/annonc/article/29/suppl_8/mdy424.019/5141601?searchresult=1

• Tribe 2: FOLFOXIRI plus bevacizumab followed by reintroduction of FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab
  • Phase 3 study of 654 patients with unresectable metastatic colorectal cancer
  • Progression free survival (primary end point) of FOLFOXIRI regimen was 18.9 months, compared with 16.2 months of the FOLFOX then FOLFIRI regimen
  • Side effects of FOLFOXIRI: febrile neutropenia, neutropenia, GI toxicities
  • https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00122-9/fulltext

• Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomized, double-blind, placebo-controlled, phase 3 trial
  • Phase 3 study included 506 patients with metastatic gastric cancer
  • Trifluridine/tipiracil (oral drug) provided a 2-month overall survival advantage (primary end point), compared with placebo
  • Major side effect: neutropenia
  • https://www.ncbi.nlm.nih.gov/pubmed/30355453

• Safety and clinical activity of 1L atezolizumab plus bevacizumab in a phase 1b study in hepatocellular carcinoma (HCC)
  • Phase 1B study included 100 patients with HCC who had not received prior therapy
  • Disease control rate was high as was duration of response
  • Primary outcomes included safety and efficacy
  • The overall response rate was 34% and the most common side effect was hypertension
  • http://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.4074

In this episode, David Henry, MD, welcomes Daniel G. Haller, MD, to rehash research from ESMO 2018 as well as the way the meeting itself was run.

And Ilana Yurkiewicz, MD, stops by for this week’s Clinical Correlation. Dr. Yurkiewicz is a hematology fellow at Stanford and also is a columnist at MDedge Hematology/Oncology. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

SHOW NOTES

By Emily Bryer, DO
Resident in the department of internal medicine, University of Pennsylvania Health System

• CheckMate 142: Durable clinical benefit with nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite high (MSI-H) and non-MSI-H colon cancer
  • Phase 2 study included 45 patients with metastatic colorectal cancer
  • Overall response rate (primary end point) was 60% and disease control rate was 84%
  • Almost every patient had some response and the therapy was well-tolerated
  • https://academic.oup.com/annonc/article/29/suppl_8/mdy424.019/5141601?searchresult=1

• Tribe 2: FOLFOXIRI plus bevacizumab followed by reintroduction of FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab
  • Phase 3 study of 654 patients with unresectable metastatic colorectal cancer
  • Progression free survival (primary end point) of FOLFOXIRI regimen was 18.9 months, compared with 16.2 months of the FOLFOX then FOLFIRI regimen
  • Side effects of FOLFOXIRI: febrile neutropenia, neutropenia, GI toxicities
  • https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00122-9/fulltext

• Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomized, double-blind, placebo-controlled, phase 3 trial
  • Phase 3 study included 506 patients with metastatic gastric cancer
  • Trifluridine/tipiracil (oral drug) provided a 2-month overall survival advantage (primary end point), compared with placebo
  • Major side effect: neutropenia
  • https://www.ncbi.nlm.nih.gov/pubmed/30355453

• Safety and clinical activity of 1L atezolizumab plus bevacizumab in a phase 1b study in hepatocellular carcinoma (HCC)
  • Phase 1B study included 100 patients with HCC who had not received prior therapy
  • Disease control rate was high as was duration of response
  • Primary outcomes included safety and efficacy
  • The overall response rate was 34% and the most common side effect was hypertension
  • http://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.4074

In this episode, David Henry, MD, welcomes Daniel G. Haller, MD, to rehash research from ESMO 2018 as well as the way the meeting itself was run.

And Ilana Yurkiewicz, MD, stops by for this week’s Clinical Correlation. Dr. Yurkiewicz is a hematology fellow at Stanford and also is a columnist at MDedge Hematology/Oncology. More from Dr. Yurkiewicz here.

Subscribe to Blood & Cancer here:

Apple Podcasts
Google Podcasts

SHOW NOTES

By Emily Bryer, DO
Resident in the department of internal medicine, University of Pennsylvania Health System

• CheckMate 142: Durable clinical benefit with nivolumab plus low-dose ipilimumab as first-line therapy in microsatellite high (MSI-H) and non-MSI-H colon cancer
  • Phase 2 study included 45 patients with metastatic colorectal cancer
  • Overall response rate (primary end point) was 60% and disease control rate was 84%
  • Almost every patient had some response and the therapy was well-tolerated
  • https://academic.oup.com/annonc/article/29/suppl_8/mdy424.019/5141601?searchresult=1

• Tribe 2: FOLFOXIRI plus bevacizumab followed by reintroduction of FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab
  • Phase 3 study of 654 patients with unresectable metastatic colorectal cancer
  • Progression free survival (primary end point) of FOLFOXIRI regimen was 18.9 months, compared with 16.2 months of the FOLFOX then FOLFIRI regimen
  • Side effects of FOLFOXIRI: febrile neutropenia, neutropenia, GI toxicities
  • https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00122-9/fulltext

• Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomized, double-blind, placebo-controlled, phase 3 trial
  • Phase 3 study included 506 patients with metastatic gastric cancer
  • Trifluridine/tipiracil (oral drug) provided a 2-month overall survival advantage (primary end point), compared with placebo
  • Major side effect: neutropenia
  • https://www.ncbi.nlm.nih.gov/pubmed/30355453

• Safety and clinical activity of 1L atezolizumab plus bevacizumab in a phase 1b study in hepatocellular carcinoma (HCC)
  • Phase 1B study included 100 patients with HCC who had not received prior therapy
  • Disease control rate was high as was duration of response
  • Primary outcomes included safety and efficacy
  • The overall response rate was 34% and the most common side effect was hypertension
  • http://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.4074

Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.

The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.

“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.

It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.


With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.

“But also, RA characteristics played a big role,” he said.

Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).

Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.

To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.

The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.

“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.

As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.

Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.

Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.

Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).

The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:

• CVD screening every 5 years.
• Use of a 1.5 multiplier for risk scores.
• Secondary screening with imaging for select patients.
• Management of traditional risk factors according to local guidelines.
• Minimization of the use of NSAIDs and corticosteroids.
• Emphasis on lifestyle management.

Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.

“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.

That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.

He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.

“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.

A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.

For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.

Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.

Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.

Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.

[email protected]

Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.

The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.

“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.

It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.


With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.

“But also, RA characteristics played a big role,” he said.

Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).

Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.

To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.

The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.

“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.

As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.

Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.

Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.

Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).

The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:

• CVD screening every 5 years.
• Use of a 1.5 multiplier for risk scores.
• Secondary screening with imaging for select patients.
• Management of traditional risk factors according to local guidelines.
• Minimization of the use of NSAIDs and corticosteroids.
• Emphasis on lifestyle management.

Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.

“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.

That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.

He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.

“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.

A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.

For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.

Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.

Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.

Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.

[email protected]

Emerging understanding of the increased incidence of cardiovascular disease in patients with rheumatoid arthritis is providing greater insight regarding mitigation of risk, according to Jon T. Giles, MD.

The mechanisms of increased cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) are multifactorial; in addition to traditional risk factors for CVD, chronically elevated levels of systemic inflammatory cytokines likely play a major role in atherogenesis and myocardial dysfunction in RA patients, and the interactions between those elevated cytokine levels and traditional risk factors also play a likely role, Dr. Giles, a rheumatologist, epidemiologist, and clinical researcher in the division of rheumatology at Columbia University, New York, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

In addition, the relationship between traditional fasting lipids and atherosclerosis is different in RA patients from that in non-RA patients, he said, noting that this has important implications for CVD screening and risk management. The phenotype of CVD in RA based on the current literature is also one involving more coronary atherosclerosis in which the atherosclerotic plaques are more inflamed.

“There’s more myocardial dysfunction,” Dr. Giles said, noting that this dysfunction may be partly mediated by more myocardial fibrosis and possibly active subclinical low-grade myocarditis.

It is possible that traditional CVD risk factors such as smoking and hypertension have a greater impact in RA patients, but it’s likely that most of the differences are related to RA-specific factors such as autoimmunity, inflammation, and genetics, as well as some nontraditional CVD risk factors such as stress, anxiety, and depression that may be increased in RA patients, he noted.


With respect to traditional CVD risk factors, a recent study of more than 5,600 RA patients without CVD who were followed for an average of almost 6 years at 13 centers in Europe and the United States showed that 389 experienced CVD events, and the most common CVD risk factors in those patients were smoking – particularly in men – and hypertension.

“But also, RA characteristics played a big role,” he said.

Disease activity was one of the major risk factors for CVD events in RA patients, and the traditional CVD risk factor of hyperlipidemia, and particularly elevated low-density lipoprotein (LDL) levels, had less influence in RA patients than in the general population. In men it was “a negative predictor” of CVD events, he said (Ann Rheum Dis. 2018;77:48-54).

Prior studies have also shown a “strange relationship” between lipids and CVD risk in RA patients. For example, RA patients with very low LDL cholesterol have been shown to have higher CVD event rates – a phenomenon known as the “lipid paradox” – and it may be related to inflammation, but the mechanism is unclear,” he said.

To further assess whether RA patients with abnormally low LDL cholesterol levels without the use of statin therapy had more atherosclerotic burden, Dr. Giles and his colleagues looked at more than 600 RA patients and more than 1,000 non-RA patients (Arthritis Rheumatol. 2015;67[suppl 10]:Abstract 2127). They found that RA patients did, indeed, have a greater atherosclerotic burden, which was “quite shocking,” he said.

The burden rivaled that seen in patients with LDL levels greater than 160 mg/dL, he noted.

“Interestingly, these patients did not have higher levels of inflammatory markers, and they did not have higher disease activity scores. They looked exactly the same as the rest of the RA patients,” he said, noting that investigation into why the LDL levels in these patients are so low is ongoing.

As for how atherogenic lipoproteins allow for atherosclerosis and atherogenesis to occur in the setting of low LDL in RA patients, it turns out it’s not just the amount, but also the characteristics of the lipoproteins, such as the size and oxidization of the LDL, which change in the context of systemic inflammation, he explained.

Further, during an acute-phase reaction, high-density lipoprotein (HDL) composition changes rapidly from antiatherogenic to proinflammatory.

Extensive evidence shows that endothelial function is diminished in RA, and that RA patients have these and other proatherogenic mechanisms, as well as other elements of immunity that are associated with atherogenesis, including aspects of both innate and adaptive immune function, he said.

Given the emerging understanding of CVD risk in RA, mitigation of that risk is an important consideration. In fact, the European League Against Rheumatism updated its CVD management guidelines in 2015/2016, including a statement that rheumatologists are responsible for CVD risk management in RA patients (Ann Rheum Dis. 2017;76:17-28).

The guidelines are intended for all inflammatory arthritis, and the recommendation with the strongest level of evidence relates to optimization of disease activity. Also recommended are:

• CVD screening every 5 years.
• Use of a 1.5 multiplier for risk scores.
• Secondary screening with imaging for select patients.
• Management of traditional risk factors according to local guidelines.
• Minimization of the use of NSAIDs and corticosteroids.
• Emphasis on lifestyle management.

Importantly, research has suggested that screening for hyperlipidemia is substandard in RA, and that standard risk stratification tools underperform in the setting of RA, he said.

“So my approach, and this is not evidence based yet ... comes down to what [a patient’s] apparent risk is. So if an RA patient is high risk based on your apparent risk prediction, then they are likely high risk and maybe even higher than estimated,” Dr. Giles said. These patients need optimization of their traditional risk factors and their inflammatory factors and should therefore receive a high-intensity statin regardless of lipid levels, he said.

That means atorvastatin at a dose of at least 40 mg or rosuvastatin at a dose of at least 20 mg, he said, adding that some studies have suggested that statins work as well in RA patients as in non-RA patients, and that RA patients with CVD risk do better with a statin than without.

He considers patients who have intermediate risk based on the risk calculation to actually be high risk in most cases, and they, too, need maximal optimization of traditional CVD risk factors and inflammatory factors.

“Consider one-time secondary imaging for all of these patients,” he advised, noting that a coronary calcium score from a chest CT scan is a good option that has low radiation, can be quantified, and is increasingly covered by insurance.

A coronary calcium score of 0 on chest CT is highly reassuring, and a score that is greater than what is expected for age, gender, and/or race can help define the intensity of intervention, he said.

For example, if a patient’s score is 300 but should be 50, that patient should be treated as if he or she has coronary artery disease. Patients with high scores in general – particularly those with scores over 300 – should also be maximally managed, he said.

Patients at low risk based on risk calculations usually are low risk, but some can be high risk, so again, maximal optimization of risk factors is recommended.

Secondary imaging can be considered in some of these patients, and while it’s not entirely clear which are at greatest risk, Dr. Giles said he recommends screening those with treatment-resistant active disease, those with high disease severity, and those with abnormally low LDL.

Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.

[email protected]