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

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

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

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

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

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

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

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

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

Prior research

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

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

Other past studies include:

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

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

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

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

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

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

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

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

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

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

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

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

Prior research

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

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

Other past studies include:

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

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

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

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

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

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

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

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

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

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

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

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

Prior research

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

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

Other past studies include:

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

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

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

A red blood cell–based platform delivered a potent antibiotic targeted to Escherichia coli in a preclinical trial.

Over several years, “we developed experimental and computational techniques to study how proteins and drugs interact with membranes,” Hannah Krivić, a graduate student, and Maikel C. Rheinstädter, PhD, a professor of physics, both at McMaster University in Hamilton, Ont., told this news organization.

In earlier work, these researchers investigated how antibiotics target bacterial membranes and how those membranes enable the development of antibiotic resistance. Then, they said, “we started to ... manipulate membranes by tuning their properties [with] synthetic lipid molecules to create ‘hybrid’ membranes – that is, functionalized biological membranes with optimized properties.

“We are now using this approach to functionalize red blood cells by using them as drug carriers. We optimize these cells to carry certain loads, such as drug molecules, and anchor proteins in their membranes that target receptors in bacteria to selectively and efficiently deliver that load.”

The strategy, they said, “has become a universal red blood cell–based delivery platform that we call ‘smart blood’ ... that can safely and selectively deliver antibiotics to certain bacterial targets.”

The platform currently is being tested in vitro, and in vivo testing is slated to begin in early 2023. Their study was published online in ACS Infectious Diseases.
 

Optimizing dosing

Polymyxin B (PmB) is one of a few potent antibiotics with promising efficacy against drug-resistant bacteria such as E. coli. PmB, however, is widely considered a treatment of last resort because of its toxic side effects (which include nephrotoxicity, neurotoxicity, and neuromuscular blockade) particularly at higher doses.

The researchers hypothesized that targeted delivery of PmB might lead to optimized dosing and potentially reduce the need for higher or repeated doses. In the current study, they tested the ability of the smart blood platform to deliver PmB to E. coli.

Creating “erythro-PmBs” involves removing the inner components of red blood cells, loading the cells with PmB, and coating the cell membranes (liposomes) with antibacterial (in this case, anti–E. coli) antibodies.

The in vitro experiments showed that the cells could be loaded with PmB and retain and selectively deliver the drug to E. coli, with no apparent hemolytic activity or nephrotoxicity. Specifically, the erythro-PmBs had a loading efficiency of approximately 90% and delivered PmB to E. coli with values for the minimum inhibitory concentration that were comparable with those of free PmB.

“In contrast to drug-delivery systems based on synthetic carriers, our erythrocytes have a high biocompatibility and can stay in circulation in the body for several weeks to provide a sustained and targeted release of the drug,” said Ms. Krivić and Dr. Rheinstädter. “This [profile] can make existing drugs safer by, for instance, increasing their efficacy while at the same time lowering the required dosage, thereby reducing side effects.”

The researchers are now exploring the ability of the smart blood platform to deliver neurotrophic factors across the blood-brain barrier to potentially treat neurodegenerative diseases. Their approach is identical to that used in the current study, they said, except in this case, the red blood cell membranes are designed to deliver neurotrophic factors specifically to the blood-brain barrier.
 

‘Certainly promising’

David W. Deamer, PhD, research professor of biomolecular engineering at the University of California, Santa Cruz, said in a comment: “This is certainly promising. The erythro-PmBs have a greater loading capacity and longer circulation time than ordinary liposomes used for drug delivery. They can also be prepared with specific antibodies so that the antibiotic is delivered more directly when they bind to bacterial pathogens.”

The effect on bacterial growth, however, was tested in a model system, not in an actual infection, he said, adding that an important next step will be to perform animal testing. “One of the simplest tests is induced sepsis in mice, which mimics a burst appendix. If the erythro-PmBs can treat sepsis effectively, it will be an encouraging sign that they have potential therapeutic value. It will also be interesting to see whether the antigens responsible for ABO blood groups are retained on the surfaces of the erythro-PmBs. If they are, it might be necessary to match donor blood to that of the recipient.

“Getting a product ready for clinical use will require partnership with a major pharmaceutical firm, several years of animal testing, and then several more years carrying out phase 1, 2, and 3 clinical trials in human patients,” Dr. Deamer concluded. 

No commercial funding was disclosed. Ms. Krivić, Dr. Rheinstädter, and Dr. Deamer reported no conflicts of interest.

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

A red blood cell–based platform delivered a potent antibiotic targeted to Escherichia coli in a preclinical trial.

Over several years, “we developed experimental and computational techniques to study how proteins and drugs interact with membranes,” Hannah Krivić, a graduate student, and Maikel C. Rheinstädter, PhD, a professor of physics, both at McMaster University in Hamilton, Ont., told this news organization.

In earlier work, these researchers investigated how antibiotics target bacterial membranes and how those membranes enable the development of antibiotic resistance. Then, they said, “we started to ... manipulate membranes by tuning their properties [with] synthetic lipid molecules to create ‘hybrid’ membranes – that is, functionalized biological membranes with optimized properties.

“We are now using this approach to functionalize red blood cells by using them as drug carriers. We optimize these cells to carry certain loads, such as drug molecules, and anchor proteins in their membranes that target receptors in bacteria to selectively and efficiently deliver that load.”

The strategy, they said, “has become a universal red blood cell–based delivery platform that we call ‘smart blood’ ... that can safely and selectively deliver antibiotics to certain bacterial targets.”

The platform currently is being tested in vitro, and in vivo testing is slated to begin in early 2023. Their study was published online in ACS Infectious Diseases.
 

Optimizing dosing

Polymyxin B (PmB) is one of a few potent antibiotics with promising efficacy against drug-resistant bacteria such as E. coli. PmB, however, is widely considered a treatment of last resort because of its toxic side effects (which include nephrotoxicity, neurotoxicity, and neuromuscular blockade) particularly at higher doses.

The researchers hypothesized that targeted delivery of PmB might lead to optimized dosing and potentially reduce the need for higher or repeated doses. In the current study, they tested the ability of the smart blood platform to deliver PmB to E. coli.

Creating “erythro-PmBs” involves removing the inner components of red blood cells, loading the cells with PmB, and coating the cell membranes (liposomes) with antibacterial (in this case, anti–E. coli) antibodies.

The in vitro experiments showed that the cells could be loaded with PmB and retain and selectively deliver the drug to E. coli, with no apparent hemolytic activity or nephrotoxicity. Specifically, the erythro-PmBs had a loading efficiency of approximately 90% and delivered PmB to E. coli with values for the minimum inhibitory concentration that were comparable with those of free PmB.

“In contrast to drug-delivery systems based on synthetic carriers, our erythrocytes have a high biocompatibility and can stay in circulation in the body for several weeks to provide a sustained and targeted release of the drug,” said Ms. Krivić and Dr. Rheinstädter. “This [profile] can make existing drugs safer by, for instance, increasing their efficacy while at the same time lowering the required dosage, thereby reducing side effects.”

The researchers are now exploring the ability of the smart blood platform to deliver neurotrophic factors across the blood-brain barrier to potentially treat neurodegenerative diseases. Their approach is identical to that used in the current study, they said, except in this case, the red blood cell membranes are designed to deliver neurotrophic factors specifically to the blood-brain barrier.
 

‘Certainly promising’

David W. Deamer, PhD, research professor of biomolecular engineering at the University of California, Santa Cruz, said in a comment: “This is certainly promising. The erythro-PmBs have a greater loading capacity and longer circulation time than ordinary liposomes used for drug delivery. They can also be prepared with specific antibodies so that the antibiotic is delivered more directly when they bind to bacterial pathogens.”

The effect on bacterial growth, however, was tested in a model system, not in an actual infection, he said, adding that an important next step will be to perform animal testing. “One of the simplest tests is induced sepsis in mice, which mimics a burst appendix. If the erythro-PmBs can treat sepsis effectively, it will be an encouraging sign that they have potential therapeutic value. It will also be interesting to see whether the antigens responsible for ABO blood groups are retained on the surfaces of the erythro-PmBs. If they are, it might be necessary to match donor blood to that of the recipient.

“Getting a product ready for clinical use will require partnership with a major pharmaceutical firm, several years of animal testing, and then several more years carrying out phase 1, 2, and 3 clinical trials in human patients,” Dr. Deamer concluded. 

No commercial funding was disclosed. Ms. Krivić, Dr. Rheinstädter, and Dr. Deamer reported no conflicts of interest.

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

A red blood cell–based platform delivered a potent antibiotic targeted to Escherichia coli in a preclinical trial.

Over several years, “we developed experimental and computational techniques to study how proteins and drugs interact with membranes,” Hannah Krivić, a graduate student, and Maikel C. Rheinstädter, PhD, a professor of physics, both at McMaster University in Hamilton, Ont., told this news organization.

In earlier work, these researchers investigated how antibiotics target bacterial membranes and how those membranes enable the development of antibiotic resistance. Then, they said, “we started to ... manipulate membranes by tuning their properties [with] synthetic lipid molecules to create ‘hybrid’ membranes – that is, functionalized biological membranes with optimized properties.

“We are now using this approach to functionalize red blood cells by using them as drug carriers. We optimize these cells to carry certain loads, such as drug molecules, and anchor proteins in their membranes that target receptors in bacteria to selectively and efficiently deliver that load.”

The strategy, they said, “has become a universal red blood cell–based delivery platform that we call ‘smart blood’ ... that can safely and selectively deliver antibiotics to certain bacterial targets.”

The platform currently is being tested in vitro, and in vivo testing is slated to begin in early 2023. Their study was published online in ACS Infectious Diseases.
 

Optimizing dosing

Polymyxin B (PmB) is one of a few potent antibiotics with promising efficacy against drug-resistant bacteria such as E. coli. PmB, however, is widely considered a treatment of last resort because of its toxic side effects (which include nephrotoxicity, neurotoxicity, and neuromuscular blockade) particularly at higher doses.

The researchers hypothesized that targeted delivery of PmB might lead to optimized dosing and potentially reduce the need for higher or repeated doses. In the current study, they tested the ability of the smart blood platform to deliver PmB to E. coli.

Creating “erythro-PmBs” involves removing the inner components of red blood cells, loading the cells with PmB, and coating the cell membranes (liposomes) with antibacterial (in this case, anti–E. coli) antibodies.

The in vitro experiments showed that the cells could be loaded with PmB and retain and selectively deliver the drug to E. coli, with no apparent hemolytic activity or nephrotoxicity. Specifically, the erythro-PmBs had a loading efficiency of approximately 90% and delivered PmB to E. coli with values for the minimum inhibitory concentration that were comparable with those of free PmB.

“In contrast to drug-delivery systems based on synthetic carriers, our erythrocytes have a high biocompatibility and can stay in circulation in the body for several weeks to provide a sustained and targeted release of the drug,” said Ms. Krivić and Dr. Rheinstädter. “This [profile] can make existing drugs safer by, for instance, increasing their efficacy while at the same time lowering the required dosage, thereby reducing side effects.”

The researchers are now exploring the ability of the smart blood platform to deliver neurotrophic factors across the blood-brain barrier to potentially treat neurodegenerative diseases. Their approach is identical to that used in the current study, they said, except in this case, the red blood cell membranes are designed to deliver neurotrophic factors specifically to the blood-brain barrier.
 

‘Certainly promising’

David W. Deamer, PhD, research professor of biomolecular engineering at the University of California, Santa Cruz, said in a comment: “This is certainly promising. The erythro-PmBs have a greater loading capacity and longer circulation time than ordinary liposomes used for drug delivery. They can also be prepared with specific antibodies so that the antibiotic is delivered more directly when they bind to bacterial pathogens.”

The effect on bacterial growth, however, was tested in a model system, not in an actual infection, he said, adding that an important next step will be to perform animal testing. “One of the simplest tests is induced sepsis in mice, which mimics a burst appendix. If the erythro-PmBs can treat sepsis effectively, it will be an encouraging sign that they have potential therapeutic value. It will also be interesting to see whether the antigens responsible for ABO blood groups are retained on the surfaces of the erythro-PmBs. If they are, it might be necessary to match donor blood to that of the recipient.

“Getting a product ready for clinical use will require partnership with a major pharmaceutical firm, several years of animal testing, and then several more years carrying out phase 1, 2, and 3 clinical trials in human patients,” Dr. Deamer concluded. 

No commercial funding was disclosed. Ms. Krivić, Dr. Rheinstädter, and Dr. Deamer reported no conflicts of interest.

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

Men across the nation took matters into their own hands by signing up for vasectomies in the days after the Supreme Court ruling in June that delegated abortion regulation to the states.

One physician has made it his mission to help. 

Charles W. Monteith Jr., MD, medical director of his own practice in Raleigh, N.C., said that before the Court’s decision in Dobbs v. Jackson , he was booked “2-3 weeks” in advance for vasectomies. 

“Now I am booked out 3 months,” he said.

In September, Dr. Monteith launched a training program for physicians interested in providing vasectomies in their offices. The course, which Dr. Monteith conceived in 2021 before the Supreme Court’s latest ruling, offers one-on-one training and mentorship for physicians who want to learn to perform minimally invasive vasectomies under local anesthesia. 

In addition to training, Dr. Monteith provides all the necessary equipment, including eye loupes, exam room surgical furniture, and instrument sterilization system. The program can be completed over 4 weekends and costs $38,000; participants typically perform 40 vasectomy procedures during the training period. 

Dr. Monteith, who trained in obstetrics and gynecology, said that he has performed over 7,000 no-scalpel vasectomies since 2008. 

Requests for vasectomy consultations at the end of June – when the Dobbs decision was announced – came from men of all ages but particularly from younger men with fewer than two children, Dr. Monteith said. 

Prior to the ruling, men with no children accounted for 10% of his patient roster; now, he added, “some days, it is 80%.”

With the increase in demand came a unique opportunity for more doctors to offer the service. The majority of vasectomies in the United States, around 75%, are performed by urologists, but 25% are performed by specialists in family medicine or general surgery.

Some research shows that urologists are typically unwilling to train family physicians on the procedure, citing concerns over competition and not enough cases to go around. But Doug Stein, MD, a urologist and director of Vasectomy and Reversal Centers of Florida in Tampa, offers a similar training for physicians, most of whom are family physicians. Opening the door for more men to get a vasectomy may be a net good, according to Dr. Stein. 

“There’s a lot of trust required for vasectomy,” Dr. Stein noted. “Men are probably more likely to go to their family medicine doctor,” that they have a rapport with than a specialist they’ve never met.

Alex Shteynshlyuger, MD, director of urology at New York Urology Specialists, said that he supports family physicians performing vasectomies. However, he cautioned that like any other procedure, complications can arise, and thorough training is essential.

“While complications are not common, they do occur, including pain, bleeding, infection, granuloma formation, and fistula tract,” Dr. Shteynshlyuger said. Family physicians must also know when to refer patients to a specialist.

Dr. Monteith said that safety considerations are why he designed his training program for clinicians who want to offer 10-20 vasectomies per week.

Dr. Monteith sees his work in teaching family care physicians on how to perform vasectomies similar to his previous role as medical director of Planned Parenthood of Central North Carolina. There, he helped provide family planning options, mostly to women. Now, he offers the options to men. 

“Most of our public health efforts seem to be focused on female reproduction,” Dr. Monteith said. “It is never a good idea to let specialists be the main providers of a preventive healthcare treatment or service, kind of like only allowing patients to go to a cardiologist to get a prescription for cholesterol medication. I needed to do what I could do to increase the number of providers offering easier access to vasectomy.”

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

Men across the nation took matters into their own hands by signing up for vasectomies in the days after the Supreme Court ruling in June that delegated abortion regulation to the states.

One physician has made it his mission to help. 

Charles W. Monteith Jr., MD, medical director of his own practice in Raleigh, N.C., said that before the Court’s decision in Dobbs v. Jackson , he was booked “2-3 weeks” in advance for vasectomies. 

“Now I am booked out 3 months,” he said.

In September, Dr. Monteith launched a training program for physicians interested in providing vasectomies in their offices. The course, which Dr. Monteith conceived in 2021 before the Supreme Court’s latest ruling, offers one-on-one training and mentorship for physicians who want to learn to perform minimally invasive vasectomies under local anesthesia. 

In addition to training, Dr. Monteith provides all the necessary equipment, including eye loupes, exam room surgical furniture, and instrument sterilization system. The program can be completed over 4 weekends and costs $38,000; participants typically perform 40 vasectomy procedures during the training period. 

Dr. Monteith, who trained in obstetrics and gynecology, said that he has performed over 7,000 no-scalpel vasectomies since 2008. 

Requests for vasectomy consultations at the end of June – when the Dobbs decision was announced – came from men of all ages but particularly from younger men with fewer than two children, Dr. Monteith said. 

Prior to the ruling, men with no children accounted for 10% of his patient roster; now, he added, “some days, it is 80%.”

With the increase in demand came a unique opportunity for more doctors to offer the service. The majority of vasectomies in the United States, around 75%, are performed by urologists, but 25% are performed by specialists in family medicine or general surgery.

Some research shows that urologists are typically unwilling to train family physicians on the procedure, citing concerns over competition and not enough cases to go around. But Doug Stein, MD, a urologist and director of Vasectomy and Reversal Centers of Florida in Tampa, offers a similar training for physicians, most of whom are family physicians. Opening the door for more men to get a vasectomy may be a net good, according to Dr. Stein. 

“There’s a lot of trust required for vasectomy,” Dr. Stein noted. “Men are probably more likely to go to their family medicine doctor,” that they have a rapport with than a specialist they’ve never met.

Alex Shteynshlyuger, MD, director of urology at New York Urology Specialists, said that he supports family physicians performing vasectomies. However, he cautioned that like any other procedure, complications can arise, and thorough training is essential.

“While complications are not common, they do occur, including pain, bleeding, infection, granuloma formation, and fistula tract,” Dr. Shteynshlyuger said. Family physicians must also know when to refer patients to a specialist.

Dr. Monteith said that safety considerations are why he designed his training program for clinicians who want to offer 10-20 vasectomies per week.

Dr. Monteith sees his work in teaching family care physicians on how to perform vasectomies similar to his previous role as medical director of Planned Parenthood of Central North Carolina. There, he helped provide family planning options, mostly to women. Now, he offers the options to men. 

“Most of our public health efforts seem to be focused on female reproduction,” Dr. Monteith said. “It is never a good idea to let specialists be the main providers of a preventive healthcare treatment or service, kind of like only allowing patients to go to a cardiologist to get a prescription for cholesterol medication. I needed to do what I could do to increase the number of providers offering easier access to vasectomy.”

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

Men across the nation took matters into their own hands by signing up for vasectomies in the days after the Supreme Court ruling in June that delegated abortion regulation to the states.

One physician has made it his mission to help. 

Charles W. Monteith Jr., MD, medical director of his own practice in Raleigh, N.C., said that before the Court’s decision in Dobbs v. Jackson , he was booked “2-3 weeks” in advance for vasectomies. 

“Now I am booked out 3 months,” he said.

In September, Dr. Monteith launched a training program for physicians interested in providing vasectomies in their offices. The course, which Dr. Monteith conceived in 2021 before the Supreme Court’s latest ruling, offers one-on-one training and mentorship for physicians who want to learn to perform minimally invasive vasectomies under local anesthesia. 

In addition to training, Dr. Monteith provides all the necessary equipment, including eye loupes, exam room surgical furniture, and instrument sterilization system. The program can be completed over 4 weekends and costs $38,000; participants typically perform 40 vasectomy procedures during the training period. 

Dr. Monteith, who trained in obstetrics and gynecology, said that he has performed over 7,000 no-scalpel vasectomies since 2008. 

Requests for vasectomy consultations at the end of June – when the Dobbs decision was announced – came from men of all ages but particularly from younger men with fewer than two children, Dr. Monteith said. 

Prior to the ruling, men with no children accounted for 10% of his patient roster; now, he added, “some days, it is 80%.”

With the increase in demand came a unique opportunity for more doctors to offer the service. The majority of vasectomies in the United States, around 75%, are performed by urologists, but 25% are performed by specialists in family medicine or general surgery.

Some research shows that urologists are typically unwilling to train family physicians on the procedure, citing concerns over competition and not enough cases to go around. But Doug Stein, MD, a urologist and director of Vasectomy and Reversal Centers of Florida in Tampa, offers a similar training for physicians, most of whom are family physicians. Opening the door for more men to get a vasectomy may be a net good, according to Dr. Stein. 

“There’s a lot of trust required for vasectomy,” Dr. Stein noted. “Men are probably more likely to go to their family medicine doctor,” that they have a rapport with than a specialist they’ve never met.

Alex Shteynshlyuger, MD, director of urology at New York Urology Specialists, said that he supports family physicians performing vasectomies. However, he cautioned that like any other procedure, complications can arise, and thorough training is essential.

“While complications are not common, they do occur, including pain, bleeding, infection, granuloma formation, and fistula tract,” Dr. Shteynshlyuger said. Family physicians must also know when to refer patients to a specialist.

Dr. Monteith said that safety considerations are why he designed his training program for clinicians who want to offer 10-20 vasectomies per week.

Dr. Monteith sees his work in teaching family care physicians on how to perform vasectomies similar to his previous role as medical director of Planned Parenthood of Central North Carolina. There, he helped provide family planning options, mostly to women. Now, he offers the options to men. 

“Most of our public health efforts seem to be focused on female reproduction,” Dr. Monteith said. “It is never a good idea to let specialists be the main providers of a preventive healthcare treatment or service, kind of like only allowing patients to go to a cardiologist to get a prescription for cholesterol medication. I needed to do what I could do to increase the number of providers offering easier access to vasectomy.”

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

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

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

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

Brain wave recordings obtained during cardiopulmonary resuscitation (CPR) offer support to near-death experiences subjectively reported by some people who survive cardiac arrest, according to a novel new study.

“These recalled experiences and brain wave changes may be the first signs of the so-called ‘near-death’ experience, and we have captured them for the first time in a large study,” lead investigator Sam Parnia, MD, PhD, with NYU Langone Health, said in a news release.

Identifying measurable electrical signs of lucid and heightened brain activity during CPR, coupled with stories of recalled near-death experiences, suggests that the human sense of self and consciousness, much like other biological body functions, may not stop completely around the time of death, Dr. Parnia added.

He presented the findings Nov. 6 at a resuscitation science symposium at the American Heart Association scientific sessions.
 

The AWARE II study

“For years, some people in cardiac arrest have reported being lucid, often with a heightened sense of consciousness, while seemingly unconscious and on the brink of death,” Dr. Parnia noted in an interview.

“Yet, no one’s ever be able to prove it and a lot of people have dismissed these experiences, thinking it’s all just a trick on the brain,” Dr. Parnia said.

In a first-of-its-kind study, Dr. Parnia and colleagues examined consciousness and its underlying electrocortical biomarkers during CPR for in-hospital cardiac arrest (IHCA).

They incorporated independent audiovisual testing of awareness with continuous real-time EEG and cerebral oxygenation (rSO₂) monitoring into CPR.

Only 53 of the 567 IHCA patients survived (9.3%). Among the 28 (52.8%) IHCA survivors who completed interviews, 11 (39.3%) reported unique, lucid experiences during resuscitation.

These experiences included a perception of separation from one’s body, observing events without pain or distress, and an awareness and meaningful evaluation of life, including of their actions, intentions, and thoughts toward others.

“These lucid experiences of death are not hallucinations or delusions. They cannot be considered a trick of a disordered or dying brain, but rather a unique human experience that emerges on the brink of death,” Dr. Parnia said. 

And what’s “fascinating,” he added, is that despite marked cerebral ischemia (mean regional oxygen saturation [rSO₂]  43%), near-normal/physiologic EEG activity (gamma, delta, theta, alpha, and beta rhythms) consistent with consciousness and a possible resumption of a network-level of cognitive and neuronal activity emerged for as long as 35-60 minutes into CPR.

Some of these brain waves normally occur when people are conscious and performing higher mental functions, including thinking, memory retrieval, and conscious perception, he said.
 

‘Seismic shift’ in understanding of death

This is the first time such biomarkers of consciousness have been identified during cardiac arrest and CPR, Dr. Parnia said.

He said further study is needed to more precisely define biomarkers of what is considered to be clinical consciousness and the recalled experience of death, and to monitor the long-term psychological effects of resuscitation after cardiac arrest.

“Our understanding of death has gone through a seismic shift in the last few years,” he said.

“The biological discoveries around death and the postmortem period are completely different to the social conventions that we have about death. That is, we perceive of death as being the end, but actually what we’re finding is that brain cells don’t die immediately. They die very slowly over many hours of time,” Dr. Parnia noted.

Reached for comment, Ajmal Zemmar, MD, PhD, of University of Louisville (Ky.), noted that several studies, including this one, “challenge the traditional way that we think of death – that when the heart stops beating that’s when we die.”

The observation that during cardiac arrest and CPR, the brain waves are still normal for up to an hour is “fairly remarkable,” Dr. Zemmar told this news organization.

“However, whether there is conscious perception or not is very hard to answer,” he cautioned. 

“This type of research tries to bridge the objective EEG recordings with the subjective description you get from the patient, but it’s hard to know when conscious perception stops,” he said.

Funding and support for the study were provided by NYU Langone Health, The John Templeton Foundation, and the UK Resuscitation Council, and National Institutes for Health Research. Dr. Parnia and Dr. Zemmar reported no relevant financial relationships.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sacral nerve stimulation (SNS) is a therapeutic procedure that could be used to help women with sexual dysfunction. However, the benefits of this method in this indication should still be reviewed in high-quality studies with sexual function as the primary endpoint, Erik Allemeyer, MD, PhD, a proctologist at the Niels Stensen Clinics in Georgsmarienhütte, Germany, and colleagues wrote in a recent journal article.

The World Health Organization defines sexual health as physical, emotional, mental, and social well-being in relation to sexuality. There are extensive investigations that verify the considerable importance of sexual function on a person’s quality of life. It therefore follows that therapy may be required if an individual is experiencing sexual dysfunction.

According to the authors, there are diverse data on the frequency of sexual dysfunction in women, in part because of heterogeneous definitions. The prevalence ranges between 26% and 91%. The estimated prevalence of orgasm difficulties in particular ranges from 16% to 25%. Sexual dysfunction can therefore be said to be a clinically significant problem.

It was recently discovered that SNS, which has only been used for other conditions so far, could also be an option for women with sexual dysfunction. According to Dr. Allemeyer and coauthors, SNS was first described in 1988 as a therapeutic alternative for patients with neurogenic bladder and has been approved in Europe since 1994. As a minimally invasive therapy for urge incontinence, idiopathic pelvic pain, and for nonobstructive urinary retention, SNS can now be used to treat a wide spectrum of conditions in urology and urogynecology. After the successful stimulation treatment of fecal incontinence was first described in 1995, the procedure has also been used in coloproctology.
 

Tested before implantation

In SNS, sacral nerve roots (S3 and S4) are permanently stimulated via a percutaneously implanted electrode. At first, the effect is reviewed using a test electrode and an external impulse generator over a period of a few weeks. Only if the test stimulation significantly alleviates symptoms can the indication for full implantation be issued, wrote the authors.

The positive effects on sexual function could be seen, even in the early years of stimulation therapy, when it was used for urinary and fecal incontinence as well as for idiopathic pelvic pain, they added. They have now summarized and discussed the current state of research on the potential effects of SNS on women’s sexual function in a literature review.
 

Systematic study analysis

To do this, they analyzed 16 studies, which included a total of 662 women, that reviewed the effect of SNS on sexual function when the treatment was being used in other indications. The overwhelming majority of data relates to urologic indications for SNS (such as overactive bladder, chronic retention, and idiopathic pelvic pain). In contrast, the SNS indication was rarely issued for fecal incontinence (9.1% of SNS indications or 61 patients). The most often used tool to assess the effect is the validated Female Sexual Function Index. The indicators covered in this index are “desire,” “arousal,” “lubrication,” “orgasm,” and “satisfaction.”

According to Dr. Allemeyer and coauthors, the analysis revealed evidence of significantly improved sexual function. It was unclear, however, whether this improvement was a primary or secondary effect of the SNS. All the original works and reviews expressly indicated that there was no proof of a primary effect of SNS on sexual function.

The mode of action of SNS and the immediate anatomic and physiologic link between the functions of urination, urinary incontinence, pelvic pain, fecal incontinence, and sexual function suggest a possible primary effect of SNS on sexual function, wrote the authors. However, no investigations use sexual function as the primary outcome parameter of SNS. This outcome should be reviewed in high-quality studies with sexual function as the primary endpoint.
 

An experimental therapy

According to Dr. Allemeyer and colleagues, two practical conclusions can be drawn from the study data available to date:

A possible primary effect of SNS on sexual function should be reviewed in high-quality, prospective studies that include detailed analyses of the different aspects of sexual dysfunction in both sexes.

An offer for trial-based SNS for sexual dysfunction should be made only at experienced sites with a multidisciplinary team of sex therapists and medical specialists and only after available therapy options have been exhausted and initially only within systematic studies.

This article was translated from Univadis Germany and a version appeared on Medscape.com.

Sacral nerve stimulation (SNS) is a therapeutic procedure that could be used to help women with sexual dysfunction. However, the benefits of this method in this indication should still be reviewed in high-quality studies with sexual function as the primary endpoint, Erik Allemeyer, MD, PhD, a proctologist at the Niels Stensen Clinics in Georgsmarienhütte, Germany, and colleagues wrote in a recent journal article.

The World Health Organization defines sexual health as physical, emotional, mental, and social well-being in relation to sexuality. There are extensive investigations that verify the considerable importance of sexual function on a person’s quality of life. It therefore follows that therapy may be required if an individual is experiencing sexual dysfunction.

According to the authors, there are diverse data on the frequency of sexual dysfunction in women, in part because of heterogeneous definitions. The prevalence ranges between 26% and 91%. The estimated prevalence of orgasm difficulties in particular ranges from 16% to 25%. Sexual dysfunction can therefore be said to be a clinically significant problem.

It was recently discovered that SNS, which has only been used for other conditions so far, could also be an option for women with sexual dysfunction. According to Dr. Allemeyer and coauthors, SNS was first described in 1988 as a therapeutic alternative for patients with neurogenic bladder and has been approved in Europe since 1994. As a minimally invasive therapy for urge incontinence, idiopathic pelvic pain, and for nonobstructive urinary retention, SNS can now be used to treat a wide spectrum of conditions in urology and urogynecology. After the successful stimulation treatment of fecal incontinence was first described in 1995, the procedure has also been used in coloproctology.
 

Tested before implantation

In SNS, sacral nerve roots (S3 and S4) are permanently stimulated via a percutaneously implanted electrode. At first, the effect is reviewed using a test electrode and an external impulse generator over a period of a few weeks. Only if the test stimulation significantly alleviates symptoms can the indication for full implantation be issued, wrote the authors.

The positive effects on sexual function could be seen, even in the early years of stimulation therapy, when it was used for urinary and fecal incontinence as well as for idiopathic pelvic pain, they added. They have now summarized and discussed the current state of research on the potential effects of SNS on women’s sexual function in a literature review.
 

Systematic study analysis

To do this, they analyzed 16 studies, which included a total of 662 women, that reviewed the effect of SNS on sexual function when the treatment was being used in other indications. The overwhelming majority of data relates to urologic indications for SNS (such as overactive bladder, chronic retention, and idiopathic pelvic pain). In contrast, the SNS indication was rarely issued for fecal incontinence (9.1% of SNS indications or 61 patients). The most often used tool to assess the effect is the validated Female Sexual Function Index. The indicators covered in this index are “desire,” “arousal,” “lubrication,” “orgasm,” and “satisfaction.”

According to Dr. Allemeyer and coauthors, the analysis revealed evidence of significantly improved sexual function. It was unclear, however, whether this improvement was a primary or secondary effect of the SNS. All the original works and reviews expressly indicated that there was no proof of a primary effect of SNS on sexual function.

The mode of action of SNS and the immediate anatomic and physiologic link between the functions of urination, urinary incontinence, pelvic pain, fecal incontinence, and sexual function suggest a possible primary effect of SNS on sexual function, wrote the authors. However, no investigations use sexual function as the primary outcome parameter of SNS. This outcome should be reviewed in high-quality studies with sexual function as the primary endpoint.
 

An experimental therapy

According to Dr. Allemeyer and colleagues, two practical conclusions can be drawn from the study data available to date:

A possible primary effect of SNS on sexual function should be reviewed in high-quality, prospective studies that include detailed analyses of the different aspects of sexual dysfunction in both sexes.

An offer for trial-based SNS for sexual dysfunction should be made only at experienced sites with a multidisciplinary team of sex therapists and medical specialists and only after available therapy options have been exhausted and initially only within systematic studies.

This article was translated from Univadis Germany and a version appeared on Medscape.com.

Sacral nerve stimulation (SNS) is a therapeutic procedure that could be used to help women with sexual dysfunction. However, the benefits of this method in this indication should still be reviewed in high-quality studies with sexual function as the primary endpoint, Erik Allemeyer, MD, PhD, a proctologist at the Niels Stensen Clinics in Georgsmarienhütte, Germany, and colleagues wrote in a recent journal article.

The World Health Organization defines sexual health as physical, emotional, mental, and social well-being in relation to sexuality. There are extensive investigations that verify the considerable importance of sexual function on a person’s quality of life. It therefore follows that therapy may be required if an individual is experiencing sexual dysfunction.

According to the authors, there are diverse data on the frequency of sexual dysfunction in women, in part because of heterogeneous definitions. The prevalence ranges between 26% and 91%. The estimated prevalence of orgasm difficulties in particular ranges from 16% to 25%. Sexual dysfunction can therefore be said to be a clinically significant problem.

It was recently discovered that SNS, which has only been used for other conditions so far, could also be an option for women with sexual dysfunction. According to Dr. Allemeyer and coauthors, SNS was first described in 1988 as a therapeutic alternative for patients with neurogenic bladder and has been approved in Europe since 1994. As a minimally invasive therapy for urge incontinence, idiopathic pelvic pain, and for nonobstructive urinary retention, SNS can now be used to treat a wide spectrum of conditions in urology and urogynecology. After the successful stimulation treatment of fecal incontinence was first described in 1995, the procedure has also been used in coloproctology.
 

Tested before implantation

In SNS, sacral nerve roots (S3 and S4) are permanently stimulated via a percutaneously implanted electrode. At first, the effect is reviewed using a test electrode and an external impulse generator over a period of a few weeks. Only if the test stimulation significantly alleviates symptoms can the indication for full implantation be issued, wrote the authors.

The positive effects on sexual function could be seen, even in the early years of stimulation therapy, when it was used for urinary and fecal incontinence as well as for idiopathic pelvic pain, they added. They have now summarized and discussed the current state of research on the potential effects of SNS on women’s sexual function in a literature review.
 

Systematic study analysis

To do this, they analyzed 16 studies, which included a total of 662 women, that reviewed the effect of SNS on sexual function when the treatment was being used in other indications. The overwhelming majority of data relates to urologic indications for SNS (such as overactive bladder, chronic retention, and idiopathic pelvic pain). In contrast, the SNS indication was rarely issued for fecal incontinence (9.1% of SNS indications or 61 patients). The most often used tool to assess the effect is the validated Female Sexual Function Index. The indicators covered in this index are “desire,” “arousal,” “lubrication,” “orgasm,” and “satisfaction.”

According to Dr. Allemeyer and coauthors, the analysis revealed evidence of significantly improved sexual function. It was unclear, however, whether this improvement was a primary or secondary effect of the SNS. All the original works and reviews expressly indicated that there was no proof of a primary effect of SNS on sexual function.

The mode of action of SNS and the immediate anatomic and physiologic link between the functions of urination, urinary incontinence, pelvic pain, fecal incontinence, and sexual function suggest a possible primary effect of SNS on sexual function, wrote the authors. However, no investigations use sexual function as the primary outcome parameter of SNS. This outcome should be reviewed in high-quality studies with sexual function as the primary endpoint.
 

An experimental therapy

According to Dr. Allemeyer and colleagues, two practical conclusions can be drawn from the study data available to date:

A possible primary effect of SNS on sexual function should be reviewed in high-quality, prospective studies that include detailed analyses of the different aspects of sexual dysfunction in both sexes.

An offer for trial-based SNS for sexual dysfunction should be made only at experienced sites with a multidisciplinary team of sex therapists and medical specialists and only after available therapy options have been exhausted and initially only within systematic studies.

This article was translated from Univadis Germany and a version appeared on Medscape.com.

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

A new antibiotic for urinary tract infections is heading toward government approval.

It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.

Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.

There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.

“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.

However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.

The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.

“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.

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

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

The effectiveness of the human papillomavirus (HPV) vaccine against HPV types 16 and 18 is highly dependent on the age at which it is given. Prevalence rates have been shown to be significantly lower among girls who are vaccinated at the recommended ages of 9-12 years, compared with those who are vaccinated after their sexual debut, data from the National Health and Nutrition Examination Survey (NHANES) indicate.

“HPV vaccination does not have any therapeutic effect on HPV infections already acquired, which is more likely to explain the difference in prevalence between predebut versus postdebut recipients than a lower immune response [among older recipients],” lead study author Didem Egemen, PhD, National Cancer Institute, Rockville, Md., told this news organization in an email.

“Still, among older females, the immune response of the vaccine is likely to still be quite strong, and we would encourage vaccination [of female patients] if unvaccinated, as our paper showed that vaccination post debut will still reduce HPV 16/18 prevalence by half,” she added.

The research letter was published online in JAMA Network Open.
 

National sample evaluated

Using data from NHANES, a biennial, cross-sectional sample (cycles 2011 through 2018), the researchers identified female persons who were aged 26 years or younger in 2006, when HPV vaccination was introduced, and who were eligible for routine vaccination or “catch-up” vaccination (given between the ages of 13 and 26 years), as per recommendations from the Advisory Committee on Immunization Practices. The investigators then compared the prevalence of HPV types 16 and 18 among unvaccinated female patients, female patients who had been vaccinated prior to their sexual debut (predebut group), and those who had been vaccinated after their sexual debut (postdebut group).

They also estimated vaccine uptake among those who were eligible for routine vaccination, as well as the proportion of vaccinated female patients with respect to racial and ethnic subgroups.

In the overall cohort, the prevalence of HPV types 16 and 18 decreased by 6% (95% confidence interval, 4%-7%) in the unvaccinated group to 3% (95% CI, 1%-6%) in the postdebut group and to less than 1% (95% CI, <1%-1%) in the predebut group, Dr. Egemen and colleagues report.

In real percentages, the prevalence of HPV 16 and 18 was 89% lower in the predebut group (P < .001) but only 41% lower in the postdebut group (P = .29) compared with unvaccinated female patients. And compared with female patients who were vaccinated after their sexual debut, the prevalence of HPV 16 and 18 was reduced by 82% among those who had received the vaccine at the recommended ages of 9-12 years (P = .08).

In the current study, Dr. Egeman acknowledged that only 38% of ever-eligible female patients received the vaccine, although the prevalence increased to 56% when only female patients who were eligible for routine vaccination were taken into account. On the other hand, only 21% (95% CI, 14%-28%) of female patients eligible for routine vaccination received their first dose by age 12 years.

Indeed, the mean age on receipt of the first vaccination dose was 14.5 years (95% CI, 14.1-14.8 years), the authors note, and only 59% of girls received their first dose prior to their sexual debut. Additionally, among routine vaccination–eligible girls aged 12 years or younger in 2006, 33% were vaccinated before and 23% after their sexual debut, and the rest were not vaccinated.

Interestingly, differences in the age at which the HPV vaccine was received by race and ethnicity were negligible, the investigators point out.
 

Vaccination rates increasing

Asked to comment on the findings, Rebecca Perkins, MD, professor of obstetrics and gynecology at Boston University, Boston Medical Center, pointed out that the investigators evaluated data from 2011 to 2018. “We know that HPV vaccination rates have increased over that period and continue to increase,” she emphasized in an email to this news organization.

Physicians also know that more persons are being vaccinated between the ages of 9 and 12 than was the case at the beginning of this study. “This is good news,” she said, “as it means that more adolescents now in 2022 are benefiting fully from vaccination than they were in 2011,” she added.

At the same time, Dr. Perkins acknowledged that many persons are still missing out on the chance to receive the vaccine on time – which means they are missing out on the chance to prevent cancer.

“Making sure that all adolescents receive vaccination between the ages of 9 to 12 has the potential to prevent up to 40,000 cancers every year in the U.S., [including] the most common HPV-related cancers, such as cervical cancer in women and tongue and tonsillar cancer in men,” Dr. Perkins noted.

“Thus, it’s critical that doctors and parents get the message that you can’t vaccinate too early, only too late,” she emphasized.

Dr. Edgman and Dr. Perkins report no relevant financial relationships.

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

Birth control options have improved over the decades. Oral contraceptives are now safer, with fewer side effects. Intrauterine devices can prevent pregnancy 99.6% of the time. But no prescription drug or medical device works flawlessly, and people’s use of contraception is inexact.

“No one walks into my office and says, ‘I plan on missing a pill,’ ” said obstetrician-gynecologist Mitchell Creinin, MD.

“There is no such thing as perfect use; we are all real-life users,” said Dr. Creinin, a professor at the University of California, Davis, who wrote a widely used textbook that details contraceptive failure rates.

Even when the odds of contraception failure are small, the number of incidents can add up quickly. More than 47 million women of reproductive age in the United States use contraception, and, depending on the birth control method, hundreds of thousands of unplanned pregnancies can occur each year. With most abortions outlawed in at least 13 states and legal battles underway in others, contraceptive failures now carry bigger stakes for tens of millions of Americans.

Researchers distinguish between the perfect use of birth control, when a method is used consistently and correctly every time, and typical use, when a method is used in real-life circumstances. No birth control, short of a complete female sterilization, has a 0.00% failure rate.

The failure rate for typical use of birth control pills is 7%. For every million women taking pills, 70,000 unplanned pregnancies could occur in a year. According to the most recent data available, more than 6.5 million women ages 15 to 49 use oral contraceptives, leading to about 460,000 unplanned pregnancies.

Even seemingly minuscule failure rates of IUDs and birth control implants can lead to surprises.

An intrauterine device releases a hormone that thickens the mucus on the cervix. Sperm hit the brick wall of mucus and are unable to pass through the barrier. Implants are matchstick-sized plastic rods placed under the skin, which send a steady, low dose of hormone into the body that also thickens the cervical mucus and prevents the ovaries from releasing an egg. But not always. The hormonal IUD and implants fail to prevent pregnancy 0.1%-0.4% of the time.

Some 4.8 million women use IUDs or implants in the U.S., leading to as many as 5,000 to 20,000 unplanned pregnancies a year.

“We’ve had women come through here for abortions who had an IUD, and they were the one in a thousand,” said Gordon Low, a nurse practitioner at the Planned Parenthood in Little Rock.

Abortion has been outlawed in Arkansas since the Supreme Court’s ruling on Dobbs v. Jackson Women’s Health Organization in late June. The only exception is when a patient’s death is considered imminent.

Those stakes are the new backdrop for couples making decisions about which form of contraception to choose or calculating the chances of pregnancy.

Another complication is the belief among many that contraceptives should work all the time, every time.

“In medicine, there is never anything that is 100%,” said Régine Sitruk-Ware, MD, a reproductive endocrinologist at the Population Council, a nonprofit research organization.

All sorts of factors interfere with contraceptive efficacy, said Dr. Sitruk-Ware. Certain medications for HIV and tuberculosis and the herbal supplement St. John’s wort can disrupt the liver’s processing of birth control pills. A medical provider might insert an IUD imprecisely into the uterus. Emergency contraception, including Plan B, is less effective in women weighing more than 165 pounds because the hormone in the medication is weight-dependent.

And life is hectic.

“You may have a delay in taking your next pill,” said Dr. Sitruk-Ware, or getting to the doctor to insert “your next vaginal ring.”

Using contraception consistently and correctly lessens the chance for a failure but Alina Salganicoff, KFF’s director of women’s health policy, said that for many people access to birth control is anything but dependable. Birth control pills are needed month after month, year after year, but “the vast majority of women can only get a one- to two-month supply,” she said.

Even vasectomies can fail.

During a vasectomy, the surgeon cuts the tube that carries sperm to the semen.

The procedure is one of the most effective methods of birth control – the failure rate is 0.15% – and avoids the side effects of hormonal birth control. But even after the vas deferens is cut, cells in the body can heal themselves, including after a vasectomy.

“If you get a cut on your finger, the skin covers it back up,” said Dr. Creinin. “Depending on how big the gap is and how the procedure is done, that tube may grow back together, and that’s one of the ways in which it fails.”

Researchers are testing reversible birth control methods for men, including a hormonal gel applied to the shoulders that suppresses sperm production. Among the 350 participants in the trial and their partners, so far zero pregnancies have occurred. It’s expected to take years for the new methods to reach the market and be available to consumers. Meanwhile, vasectomies and condoms remain the only contraception available for men, who remain fertile for much of their lives.

At 13%, the typical-use failure rate of condoms is among the highest of birth control methods. Condoms play a vital role in stopping the spread of HIV and other sexually transmitted infections, but they are often misused or tear. The typical-use failure rate means that for 1 million couples using condoms, 130,000 unplanned pregnancies could occur in one year.

Navigating the failure rates of birth control medicines and medical devices is just one aspect of preventing pregnancy. Ensuring a male sexual partner uses a condom can require negotiation or persuasion skills that can be difficult to navigate, said Jennifer Evans, an assistant teaching professor and health education specialist at Northeastern University.

Historically, women have had little to no say in whether to engage in sexual intercourse and limited autonomy over their bodies, complicating sexual-negotiation skills today, said Ms. Evans.

Part of Ms. Evans’ research focuses on men who coerce women into sex without a condom. One tactic, known as “stealthing,” is when a man puts on a condom but then removes it either before or during sexual intercourse without the other person’s knowledge or consent.

“In a lot of these stealthing cases women don’t necessarily know the condom has been used improperly,” said Ms. Evans. “It means they can’t engage in any kind of preventative behaviors like taking a Plan B or even going and getting an abortion in a timely manner.”

Ms. Evans has found that heterosexual men who engage in stealthing often have hostile attitudes toward women. They report that sex without a condom feels better or say they do it “for the thrill of engaging in a behavior they know is not OK,” she said. Ms. Evans cautions women who suspect a sexual partner will not use a condom correctly to not have sex with that person.

“The consequences were already severe before,” said Ms. Evans, “but now that Roe v. Wade has been overturned, they’re even more right now.”

This story is a collaboration between KHN and Science Friday. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Birth control options have improved over the decades. Oral contraceptives are now safer, with fewer side effects. Intrauterine devices can prevent pregnancy 99.6% of the time. But no prescription drug or medical device works flawlessly, and people’s use of contraception is inexact.

“No one walks into my office and says, ‘I plan on missing a pill,’ ” said obstetrician-gynecologist Mitchell Creinin, MD.

“There is no such thing as perfect use; we are all real-life users,” said Dr. Creinin, a professor at the University of California, Davis, who wrote a widely used textbook that details contraceptive failure rates.

Even when the odds of contraception failure are small, the number of incidents can add up quickly. More than 47 million women of reproductive age in the United States use contraception, and, depending on the birth control method, hundreds of thousands of unplanned pregnancies can occur each year. With most abortions outlawed in at least 13 states and legal battles underway in others, contraceptive failures now carry bigger stakes for tens of millions of Americans.

Researchers distinguish between the perfect use of birth control, when a method is used consistently and correctly every time, and typical use, when a method is used in real-life circumstances. No birth control, short of a complete female sterilization, has a 0.00% failure rate.

The failure rate for typical use of birth control pills is 7%. For every million women taking pills, 70,000 unplanned pregnancies could occur in a year. According to the most recent data available, more than 6.5 million women ages 15 to 49 use oral contraceptives, leading to about 460,000 unplanned pregnancies.

Even seemingly minuscule failure rates of IUDs and birth control implants can lead to surprises.

An intrauterine device releases a hormone that thickens the mucus on the cervix. Sperm hit the brick wall of mucus and are unable to pass through the barrier. Implants are matchstick-sized plastic rods placed under the skin, which send a steady, low dose of hormone into the body that also thickens the cervical mucus and prevents the ovaries from releasing an egg. But not always. The hormonal IUD and implants fail to prevent pregnancy 0.1%-0.4% of the time.

Some 4.8 million women use IUDs or implants in the U.S., leading to as many as 5,000 to 20,000 unplanned pregnancies a year.

“We’ve had women come through here for abortions who had an IUD, and they were the one in a thousand,” said Gordon Low, a nurse practitioner at the Planned Parenthood in Little Rock.

Abortion has been outlawed in Arkansas since the Supreme Court’s ruling on Dobbs v. Jackson Women’s Health Organization in late June. The only exception is when a patient’s death is considered imminent.

Those stakes are the new backdrop for couples making decisions about which form of contraception to choose or calculating the chances of pregnancy.

Another complication is the belief among many that contraceptives should work all the time, every time.

“In medicine, there is never anything that is 100%,” said Régine Sitruk-Ware, MD, a reproductive endocrinologist at the Population Council, a nonprofit research organization.

All sorts of factors interfere with contraceptive efficacy, said Dr. Sitruk-Ware. Certain medications for HIV and tuberculosis and the herbal supplement St. John’s wort can disrupt the liver’s processing of birth control pills. A medical provider might insert an IUD imprecisely into the uterus. Emergency contraception, including Plan B, is less effective in women weighing more than 165 pounds because the hormone in the medication is weight-dependent.

And life is hectic.

“You may have a delay in taking your next pill,” said Dr. Sitruk-Ware, or getting to the doctor to insert “your next vaginal ring.”

Using contraception consistently and correctly lessens the chance for a failure but Alina Salganicoff, KFF’s director of women’s health policy, said that for many people access to birth control is anything but dependable. Birth control pills are needed month after month, year after year, but “the vast majority of women can only get a one- to two-month supply,” she said.

Even vasectomies can fail.

During a vasectomy, the surgeon cuts the tube that carries sperm to the semen.

The procedure is one of the most effective methods of birth control – the failure rate is 0.15% – and avoids the side effects of hormonal birth control. But even after the vas deferens is cut, cells in the body can heal themselves, including after a vasectomy.

“If you get a cut on your finger, the skin covers it back up,” said Dr. Creinin. “Depending on how big the gap is and how the procedure is done, that tube may grow back together, and that’s one of the ways in which it fails.”

Researchers are testing reversible birth control methods for men, including a hormonal gel applied to the shoulders that suppresses sperm production. Among the 350 participants in the trial and their partners, so far zero pregnancies have occurred. It’s expected to take years for the new methods to reach the market and be available to consumers. Meanwhile, vasectomies and condoms remain the only contraception available for men, who remain fertile for much of their lives.

At 13%, the typical-use failure rate of condoms is among the highest of birth control methods. Condoms play a vital role in stopping the spread of HIV and other sexually transmitted infections, but they are often misused or tear. The typical-use failure rate means that for 1 million couples using condoms, 130,000 unplanned pregnancies could occur in one year.

Navigating the failure rates of birth control medicines and medical devices is just one aspect of preventing pregnancy. Ensuring a male sexual partner uses a condom can require negotiation or persuasion skills that can be difficult to navigate, said Jennifer Evans, an assistant teaching professor and health education specialist at Northeastern University.

Historically, women have had little to no say in whether to engage in sexual intercourse and limited autonomy over their bodies, complicating sexual-negotiation skills today, said Ms. Evans.

Part of Ms. Evans’ research focuses on men who coerce women into sex without a condom. One tactic, known as “stealthing,” is when a man puts on a condom but then removes it either before or during sexual intercourse without the other person’s knowledge or consent.

“In a lot of these stealthing cases women don’t necessarily know the condom has been used improperly,” said Ms. Evans. “It means they can’t engage in any kind of preventative behaviors like taking a Plan B or even going and getting an abortion in a timely manner.”

Ms. Evans has found that heterosexual men who engage in stealthing often have hostile attitudes toward women. They report that sex without a condom feels better or say they do it “for the thrill of engaging in a behavior they know is not OK,” she said. Ms. Evans cautions women who suspect a sexual partner will not use a condom correctly to not have sex with that person.

“The consequences were already severe before,” said Ms. Evans, “but now that Roe v. Wade has been overturned, they’re even more right now.”

This story is a collaboration between KHN and Science Friday. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Birth control options have improved over the decades. Oral contraceptives are now safer, with fewer side effects. Intrauterine devices can prevent pregnancy 99.6% of the time. But no prescription drug or medical device works flawlessly, and people’s use of contraception is inexact.

“No one walks into my office and says, ‘I plan on missing a pill,’ ” said obstetrician-gynecologist Mitchell Creinin, MD.

“There is no such thing as perfect use; we are all real-life users,” said Dr. Creinin, a professor at the University of California, Davis, who wrote a widely used textbook that details contraceptive failure rates.

Even when the odds of contraception failure are small, the number of incidents can add up quickly. More than 47 million women of reproductive age in the United States use contraception, and, depending on the birth control method, hundreds of thousands of unplanned pregnancies can occur each year. With most abortions outlawed in at least 13 states and legal battles underway in others, contraceptive failures now carry bigger stakes for tens of millions of Americans.

Researchers distinguish between the perfect use of birth control, when a method is used consistently and correctly every time, and typical use, when a method is used in real-life circumstances. No birth control, short of a complete female sterilization, has a 0.00% failure rate.

The failure rate for typical use of birth control pills is 7%. For every million women taking pills, 70,000 unplanned pregnancies could occur in a year. According to the most recent data available, more than 6.5 million women ages 15 to 49 use oral contraceptives, leading to about 460,000 unplanned pregnancies.

Even seemingly minuscule failure rates of IUDs and birth control implants can lead to surprises.

An intrauterine device releases a hormone that thickens the mucus on the cervix. Sperm hit the brick wall of mucus and are unable to pass through the barrier. Implants are matchstick-sized plastic rods placed under the skin, which send a steady, low dose of hormone into the body that also thickens the cervical mucus and prevents the ovaries from releasing an egg. But not always. The hormonal IUD and implants fail to prevent pregnancy 0.1%-0.4% of the time.

Some 4.8 million women use IUDs or implants in the U.S., leading to as many as 5,000 to 20,000 unplanned pregnancies a year.

“We’ve had women come through here for abortions who had an IUD, and they were the one in a thousand,” said Gordon Low, a nurse practitioner at the Planned Parenthood in Little Rock.

Abortion has been outlawed in Arkansas since the Supreme Court’s ruling on Dobbs v. Jackson Women’s Health Organization in late June. The only exception is when a patient’s death is considered imminent.

Those stakes are the new backdrop for couples making decisions about which form of contraception to choose or calculating the chances of pregnancy.

Another complication is the belief among many that contraceptives should work all the time, every time.

“In medicine, there is never anything that is 100%,” said Régine Sitruk-Ware, MD, a reproductive endocrinologist at the Population Council, a nonprofit research organization.

All sorts of factors interfere with contraceptive efficacy, said Dr. Sitruk-Ware. Certain medications for HIV and tuberculosis and the herbal supplement St. John’s wort can disrupt the liver’s processing of birth control pills. A medical provider might insert an IUD imprecisely into the uterus. Emergency contraception, including Plan B, is less effective in women weighing more than 165 pounds because the hormone in the medication is weight-dependent.

And life is hectic.

“You may have a delay in taking your next pill,” said Dr. Sitruk-Ware, or getting to the doctor to insert “your next vaginal ring.”

Using contraception consistently and correctly lessens the chance for a failure but Alina Salganicoff, KFF’s director of women’s health policy, said that for many people access to birth control is anything but dependable. Birth control pills are needed month after month, year after year, but “the vast majority of women can only get a one- to two-month supply,” she said.

Even vasectomies can fail.

During a vasectomy, the surgeon cuts the tube that carries sperm to the semen.

The procedure is one of the most effective methods of birth control – the failure rate is 0.15% – and avoids the side effects of hormonal birth control. But even after the vas deferens is cut, cells in the body can heal themselves, including after a vasectomy.

“If you get a cut on your finger, the skin covers it back up,” said Dr. Creinin. “Depending on how big the gap is and how the procedure is done, that tube may grow back together, and that’s one of the ways in which it fails.”

Researchers are testing reversible birth control methods for men, including a hormonal gel applied to the shoulders that suppresses sperm production. Among the 350 participants in the trial and their partners, so far zero pregnancies have occurred. It’s expected to take years for the new methods to reach the market and be available to consumers. Meanwhile, vasectomies and condoms remain the only contraception available for men, who remain fertile for much of their lives.

At 13%, the typical-use failure rate of condoms is among the highest of birth control methods. Condoms play a vital role in stopping the spread of HIV and other sexually transmitted infections, but they are often misused or tear. The typical-use failure rate means that for 1 million couples using condoms, 130,000 unplanned pregnancies could occur in one year.

Navigating the failure rates of birth control medicines and medical devices is just one aspect of preventing pregnancy. Ensuring a male sexual partner uses a condom can require negotiation or persuasion skills that can be difficult to navigate, said Jennifer Evans, an assistant teaching professor and health education specialist at Northeastern University.

Historically, women have had little to no say in whether to engage in sexual intercourse and limited autonomy over their bodies, complicating sexual-negotiation skills today, said Ms. Evans.

Part of Ms. Evans’ research focuses on men who coerce women into sex without a condom. One tactic, known as “stealthing,” is when a man puts on a condom but then removes it either before or during sexual intercourse without the other person’s knowledge or consent.

“In a lot of these stealthing cases women don’t necessarily know the condom has been used improperly,” said Ms. Evans. “It means they can’t engage in any kind of preventative behaviors like taking a Plan B or even going and getting an abortion in a timely manner.”

Ms. Evans has found that heterosexual men who engage in stealthing often have hostile attitudes toward women. They report that sex without a condom feels better or say they do it “for the thrill of engaging in a behavior they know is not OK,” she said. Ms. Evans cautions women who suspect a sexual partner will not use a condom correctly to not have sex with that person.

“The consequences were already severe before,” said Ms. Evans, “but now that Roe v. Wade has been overturned, they’re even more right now.”

This story is a collaboration between KHN and Science Friday. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.