Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Risk for severe infections significantly increased in patients who were newly diagnosed with rheumatoid arthritis (RA) after initiating biologic disease-modifying antirheumatic drugs (bDMARD).

Major finding: Over a period of 8 years, severe infection rates significantly increased in patients who were newly diagnosed with RA after initiating bDMARD (adjusted difference between pre- and post-bDMARD rates [Δ] 1.85; P  =  .001), whereas no significant change was observed in control individuals from the general population (Δ 0.12; P  =  .29).

Study details: Findings are from a population-based retrospective cohort study including 60,226 patients with newly diagnosed RA and 588,499 age- and sex-matched control individuals without any inflammatory arthritis from the general population who initiated bDMARD.

Disclosures: This study was supported by the Canadian Institute of Health Research and other sources. The authors declared no conflicts of interest.

Source: Zhou VY et al. Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: A population-based interrupted time-series analysis. Rheumatology (Oxford). 2023 (Apr 4). Doi: 10.1093/rheumatology/kead158

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Patients with rheumatoid arthritis (RA) treated with tofacitinib had a 69% lower risk of developing interstitial lung disease (ILD) than those treated with adalimumab.

Major finding: Compared with adalimumab, tofacitinib resulted in the lowest incidence of ILD (incidence rate ratio 0.43; 95% CI 0.18-1.05), followed by abatacept, tocilizumab, and rituximab. Tofacitinib was associated with a significant 69% reduced risk of developing ILD compared with adalimumab (adjusted hazard ratio 0.31; P  =  .009).

Study details: Findings are from a retrospective cohort study including 28,559 patients with RA without preexisting ILD who were newly administered adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib, of which 276 patients were diagnosed with incident ILD.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors did not report conflicts of interest.

Source: Baker MC et al. Incidence of interstitial lung disease in patients with rheumatoid arthritis treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. JAMA Netw Open. 2023;6(3):e233640 (Mar 20). Doi: 10.1001/jamanetworkopen.2023.3640

Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

Key clinical point: Continuation of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) was not superior to withdrawal in patients with rheumatoid arthritis (RA) in sustained remission with half-dose csDMARD, suggesting withdrawal of half-dose csDMARD is feasible in some patients.

Major finding: Although discontinuing vs continuing half-dose csDMARD led to a numerically higher risk for flares within 12 months (risk difference 21.5%; 95% CI −3.4% to 49.7%), more patients discontinuing vs continuing half-dose csDMARD showed no radiographic joint damage progression (risk difference 13.9%; 95% CI −10.6% to 38.3%) and regained Disease Activity Score-based remission (80.0% [95% CI 44.4%-97.5%] vs 66.7% [95% CI 9.5%-99.2%]) at the first visit after flare.

Study details: This open-label trial, a part of the ARCTIC REWIND project, included 56 patients with RA who were in sustained remission for ≥12 months with half-dose csDMARD and were randomly assigned to discontinue or continue half-dose csDMARD.

Disclosures: This study was funded by the Research Council of Norway and other sources. Several authors declared receiving research grants or personal fees from various sources.

Source: Lillegraven S et al. Discontinuation of conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis and excellent disease control. JAMA. 2023;329(12):1024-1026 (Mar 28). Doi: 10.1001/jama.2023.0492

Key clinical point: Preexisting rheumatoid arthritis (RA) did not increase the risk for mortality or severe immune-related adverse events (AE) in patients initiating immune checkpoint inhibitors for cancer treatment and thus, should not be considered as a contraindication for initiating immune checkpoint inhibitors.

Major finding: Among patients initiating immune checkpoint inhibitors for cancer treatment, those with and without preexisting RA had comparable risks for mortality (adjusted hazard ratio [aHR] 1.16; P  =  .30) and severe grade ≥3 immune-related AE (aHR 1.06; P  =  .83).

Study details: Findings are from a retrospective, comparative, cohort study including 11,901 patients who initiated immune checkpoint inhibitors for cancer treatment, of which 87 patients with preexisting RA were matched to 203 patients without preexisting autoimmune diseases (comparator group).

Disclosures: This study did not receive any specific funding. Several authors declared being employed and owning stock options or receiving partial salary support, honoraria, consulting fees, research grants, or royalties from different sources.

Source: McCarter KR et al. Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: A retrospective, comparative, cohort study. Lancet Rheumatol. 2023 (Mar 27). Doi: 10.1016/S2665-9913(23)00064-4

Key clinical point: Preexisting rheumatoid arthritis (RA) did not increase the risk for mortality or severe immune-related adverse events (AE) in patients initiating immune checkpoint inhibitors for cancer treatment and thus, should not be considered as a contraindication for initiating immune checkpoint inhibitors.

Major finding: Among patients initiating immune checkpoint inhibitors for cancer treatment, those with and without preexisting RA had comparable risks for mortality (adjusted hazard ratio [aHR] 1.16; P  =  .30) and severe grade ≥3 immune-related AE (aHR 1.06; P  =  .83).

Study details: Findings are from a retrospective, comparative, cohort study including 11,901 patients who initiated immune checkpoint inhibitors for cancer treatment, of which 87 patients with preexisting RA were matched to 203 patients without preexisting autoimmune diseases (comparator group).

Disclosures: This study did not receive any specific funding. Several authors declared being employed and owning stock options or receiving partial salary support, honoraria, consulting fees, research grants, or royalties from different sources.

Source: McCarter KR et al. Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: A retrospective, comparative, cohort study. Lancet Rheumatol. 2023 (Mar 27). Doi: 10.1016/S2665-9913(23)00064-4

Key clinical point: Preexisting rheumatoid arthritis (RA) did not increase the risk for mortality or severe immune-related adverse events (AE) in patients initiating immune checkpoint inhibitors for cancer treatment and thus, should not be considered as a contraindication for initiating immune checkpoint inhibitors.

Major finding: Among patients initiating immune checkpoint inhibitors for cancer treatment, those with and without preexisting RA had comparable risks for mortality (adjusted hazard ratio [aHR] 1.16; P  =  .30) and severe grade ≥3 immune-related AE (aHR 1.06; P  =  .83).

Study details: Findings are from a retrospective, comparative, cohort study including 11,901 patients who initiated immune checkpoint inhibitors for cancer treatment, of which 87 patients with preexisting RA were matched to 203 patients without preexisting autoimmune diseases (comparator group).

Disclosures: This study did not receive any specific funding. Several authors declared being employed and owning stock options or receiving partial salary support, honoraria, consulting fees, research grants, or royalties from different sources.

Source: McCarter KR et al. Mortality and immune-related adverse events after immune checkpoint inhibitor initiation for cancer among patients with pre-existing rheumatoid arthritis: A retrospective, comparative, cohort study. Lancet Rheumatol. 2023 (Mar 27). Doi: 10.1016/S2665-9913(23)00064-4

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – Noninvasive tests performed in midlife may help identify people who are at risk of late-onset epilepsy, a new study suggests. New data from the Framingham Heart Study show those who scored better on a neurocognitive test that measures executive function were 75% less likely to develop late-onset epilepsy.

An analysis of MRI revealed that those with higher cortical volumes also had a lower risk of epilepsy later in life, while those with higher white matter hyperintensities had an increased risk.

The study could help identify at-risk individuals years before symptoms of epilepsy appear.

“We present possible markers that could potentially identify patients at risk for developing late-onset epilepsy, even in the preclinical phase and before the clinical manifestation of conditions like stroke and dementia that are known now to be linked with the condition,” said lead investigator Maria Stefanidou, MD, assistant professor of neurology at Boston University.

The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
 

Protection against late-onset epilepsy?

Hypertension and stroke are known risk factors for late-onset epilepsy. Dementia is also a known risk factor. But in about 30% of cases, the cause of epilepsy in older individuals is unknown.

For this study, investigators analyzed data from the offspring cohort of the Framingham Heart Study. Participants were at least 45 years old; underwent neuropsychological evaluation and brain MRI; and had no prior history of stroke, dementia, or epilepsy. Cognitive measures included Visual Reproductions Delayed Recall, Logical Memory Delayed Recall, Similarities, Trail Making B-A (TrB-TrA), and the Hooper Visual Organization Test.

Participants also underwent an MRI to measure total cerebral brain volume, cortical gray matter volume, white matter hyperintensities, and hippocampal volume.

After a mean follow-up of 13.5 years, late-onset epilepsy was diagnosed in 31 of participants who underwent neuropsychological testing (n = 2,349) and in 27 of those who underwent MRI (n = 2,056).

Better performance on the TrB-TrA test (a measure of executive function, processing speed, and occult vascular injury) was associated with a reduced risk of late-onset epilepsy (adjusted hazard ratio, 0.25; P = .011).

The findings held even after adjusting for age, sex, educational level, and known risk factors for late-onset epilepsy, such as hypertension (aHR, 0.30; P = .0401).

Higher white matter hyperintensities, a measure of occult vascular injury, was associated with increased epilepsy risk (aHR, 1.5; P = .042) when adjusted only for age, sex, and education, but was no longer significant after adjusting for hypertension and other risk factors (aHR, 1.47; P = .065).

The analysis also revealed that participants with a higher cortical gray matter volume had a lower risk for late-onset epilepsy (aHR, 0.73; P = .001).

“There is increasing literature supporting that late-onset epilepsy may be secondary to accumulative occult cerebrovascular and neurodegenerative processes that occur during aging,” Dr. Stefanidou said. “Our findings likely reflect that a lesser degree of occult vascular brain injury in midlife may be protective against late-onset epilepsy.”

However, the epidemiological study points to association, not causation, Dr. Stefanidou cautions.

“Further studies will be needed to study our observations in the clinical setting,” she said.
 

‘Intriguing’ findings

Commenting on the findings, Joseph Sirven, MD, a neurologist at the Mayo Clinic in Jacksonville, Fla., said the findings are “intriguing,” but also raise some questions. “Late-onset epilepsy remains an issue for many and it’s common,” said Dr. Sirven, who has patients with late-onset epilepsy.

Dr. Sirven was particularly interested in the findings on white matter hyperintensities. “Hippocampal volumes have been used but not so much cortical volumes,” he said. “I would like to know more about how white matter changes suggest pathology that would explain epilepsy.”

Study funding was not disclosed. Dr. Stefanidou and Dr. Sirven report no relevant financial relationships.

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

BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.

The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
 

Phase 1 study

Early phase studies are largely focused on safety, but the 6-month interim data of a 12-month study showed rapid reductions in multiple biomarkers of muscle injury, reductions in anti-inflammatory markers, proteomic changes consistent with sustained effects, and a trend for functional improvement in muscle dystrophies.

Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.

In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.

The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.

For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.

“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
 

Proof of concept

In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.

In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.

At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.

The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.

On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.

As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
 

Findings deemed ‘a big deal’

These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.

“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.

“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.

Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
 

BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.

The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
 

Phase 1 study

Early phase studies are largely focused on safety, but the 6-month interim data of a 12-month study showed rapid reductions in multiple biomarkers of muscle injury, reductions in anti-inflammatory markers, proteomic changes consistent with sustained effects, and a trend for functional improvement in muscle dystrophies.

Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.

In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.

The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.

For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.

“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
 

Proof of concept

In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.

In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.

At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.

The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.

On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.

As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
 

Findings deemed ‘a big deal’

These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.

“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.

“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.

Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
 

BOSTON – Becker (BMD) and Duchenne muscle dystrophy (DMD) progress largely from irreversible contraction-induced injury of skeletal muscles, making the very positive interim results of an early-phase trial with a drug that prevents these injuries worth attention.

The phase 1b data in BMD, presented at the 2023 annual meeting of the American Academy of Neurology, were sufficiently promising that controlled phase 2 trials in both BMD and DMD are already enrolling, reported Joanne Donovan, MD, PhD, an adjunct professor at Boston University and chief medical officer of Edgewise Therapeutics, the company developing the drug.
 

Phase 1 study

Early phase studies are largely focused on safety, but the 6-month interim data of a 12-month study showed rapid reductions in multiple biomarkers of muscle injury, reductions in anti-inflammatory markers, proteomic changes consistent with sustained effects, and a trend for functional improvement in muscle dystrophies.

Moreover, the evidence of a clinical effect was achieved in adult patients with a North Star Ambulatory Assessment (NSAA) score of 15, signifying advanced disease. Only 12 patients were enrolled and there were no controls, but objective evidence of a favorable effect was generated by highly significant reductions in creatine kinase (CK) and fast skeletal muscle (TNNI2) troponin, which are both biomarkers commonly used to track muscular dystrophy progression.

In patients with BMD or DMD, a lack of dystrophin is a key pathogenic feature, according to Dr. Donovan. She explained that dystrophin in muscles connects contractile proteins to membranes and surrounding matrix. In the presence of dystrophin, muscle fibers support each other, but when this protein is absent, contraction causes injury.

The drug in development, currently identified as EDG-5506, is a selective fast myosin inhibitor. This agent was shown to prevent the muscle injury caused by lack of dystrophin in animal models of muscular dystrophy and is now showing the same effect in humans. Preservation of muscle is critical to preventing BMD and DMD progression according to several sets of data, according to Dr. Donovan.

For one, it has been shown that BMD or DMD patients with relatively preserved function as defined by a NSAA score above 32 have minimal muscle damage. As NSAA scores fall below 32 points, muscle mass diminishes and fat accumulates. In natural history studies of BMD, there is a 1.2-point decline in NSAA score over 5 years, and this tracks with muscle loss and not with other variables, such as patient age.

“Progression depends on the degree of muscle loss,” Dr. Donovan stated, providing the rationale for moving forward with EDG-5506.
 

Proof of concept

In experimental studies, modulation of fast myelin provided complete protection against muscle injury while preserving its contractile function, and this translated into protection against loss of function. Phase 1 studies in BMD patients and healthy controls have already provided evidence that EDG-5506 is well tolerated and safe, but the new phase 1b provides a proof of concept for its ability to inhibit muscle injury in BMD patients.

In this study, called ARCH, 12 adults 18 years of age or older with a dystrophin mutation and a BMD phenotype who could complete a 100-meter timed test were enrolled. The median age at entry was 32 years. Several patients had participated in a previous phase 1 safety study. The daily starting dose of 10 mg was increased from 10 mg to 15 mg at 2 months. The dose was increased again to 20 mg at 6 months, but the data presented by Dr. Donovan were restricted to the first 6 months.

At the interim 6-month analysis, creatine kinase was reduced by 40% and TINN2 was reduced by 84% (both P < 0.001). The significant reductions in these biomarkers and others, such as myoglobin, were mostly achieved within the first month, although further reductions were observed for some biomarkers subsequently.

The NSAA score at 6 months improved on average by about 1 point on treatment. Natural history studies of BMD predict a 1-point reduction in NSAA score over this period of time. The modest improvements from baseline in pain scores at 1 month were sustained at 6 months.

On the basis of a proteomic analysis, 125 proteins mostly associated with metabolic pathways consistent with muscle injury were found to be altered in BMD patients relative to healthy controls. The majority of these proteins, whether assessed collectively or individually, normalized after 1 to 2 months of treatment with EDG-5506 and have remained stable during follow-up to date, according to Dr. Donovan.

As in previous studies, the drug was well tolerated. The three most common treatment-emergent events were dizziness, somnolence, and headache. Each was reported by about 25% of patients, but no patient discontinued therapy as a result of adverse events.
 

Findings deemed ‘a big deal’

These data, despite the small number of patients in the study and the limited follow-up, “are a big deal,” according to Nicholas E. Johnson, MD, division chief, neuromuscular disorders, Virginia Commonwealth University, Richmond. He pointed out that there are no effective treatments currently for BMD, and the mechanism of action is plausible.

“I am excited about the potential of this treatment, although we clearly need longer follow-up and more patients evaluated on this treatment,” Dr. Johnson said. He said that clinicians with BMD patients should be aware of the phase 2 trial that is now recruiting adult subjects.

“Becker muscular dystrophy is highly disabling. As disease advances, most patients have very limited function,” said Dr. Johnson, emphasizing the urgent unmet need for an effective therapy.

Dr. Donovan is a full time employee of Edgewise Therapeutics, which funded this study. Dr. Johnson has financial relationships with Acceleron, Arthex, AveXis, Avidity, Biogen, Dyne Therapeutics, Entrada, Juvena, ML Bio, Sarepta Therapeutics, Triplet Therapeutics, and Vertex Pharma.
 

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

Taking a swing against arthritis

Osteoarthritis is a tough disease to manage. Exercise helps ease the stiffness and pain of the joints, but at the same time, the disease makes it difficult to do that beneficial exercise. Even a relatively simple activity like jogging can hurt more than it helps. If only there were a low-impact exercise that was incredibly popular among the generally older population who are likely to have arthritis.

We love a good golf study here at LOTME, and a group of Australian and U.K. researchers have provided. Osteoarthritis affects 2 million people in the land down under, making it the most common source of disability there. In that population, only 64% reported their physical health to be good, very good, or excellent. Among the 459 golfers with OA that the study authors surveyed, however, the percentage reporting good health rose to more than 90%.

jacoblund/Getty Images

A similar story emerged when they looked at mental health. Nearly a quarter of nongolfers with OA reported high or very high levels of psychological distress, compared with just 8% of golfers. This pattern of improved physical and mental health remained when the researchers looked at the general, non-OA population.

This isn’t the first time golf’s been connected with improved health, and previous studies have shown golf to reduce the risks of cardiovascular disease, diabetes, and obesity, among other things. Just walking one 18-hole round significantly exceeds the CDC’s recommended 150 minutes of physical activity per week. Go out multiple times a week – leaving the cart and beer at home, American golfers – and you’ll be fit for a lifetime.

The golfers on our staff, however, are still waiting for those mental health benefits to kick in. Because when we’re adding up our scorecard after that string of four double bogeys to end the round, we’re most definitely thinking: “Yes, this sport is reducing my psychological distress. I am having fun right now.”
 

Battle of the sexes’ intestines

There are, we’re sure you’ve noticed, some differences between males and females. Females, for one thing, have longer small intestines than males. Everybody knows that, right? You didn’t know? Really? … Really?

Afif Ramdhasuma/Unsplash

Well, then, we’re guessing you haven’t read “Hidden diversity: Comparative functional morphology of humans and other species” by Erin A. McKenney, PhD, of North Carolina State University, Raleigh, and associates, which just appeared in PeerJ. We couldn’t put it down, even in the shower – a real page-turner/scroller. (It’s a great way to clean a phone, for those who also like to scroll, text, or talk on the toilet.)

The researchers got out their rulers, calipers, and string and took many measurements of the digestive systems of 45 human cadavers (21 female and 24 male), which were compared with data from 10 rats, 10 pigs, and 10 bullfrogs, which had been collected (the measurements, not the animals) by undergraduate students enrolled in a comparative anatomy laboratory course at the university.

There was little intestinal-length variation among the four-legged subjects, but when it comes to humans, females have “consistently and significantly longer small intestines than males,” the investigators noted.

The women’s small intestines, almost 14 feet long on average, were about a foot longer than the men’s, which suggests that women are better able to extract nutrients from food and “supports the canalization hypothesis, which posits that women are better able to survive during periods of stress,” coauthor Amanda Hale said in a written statement from the school. The way to a man’s heart may be through his stomach, but the way to a woman’s heart is through her duodenum, it seems.

Fascinating stuff, to be sure, but the thing that really caught our eye in the PeerJ article was the authors’ suggestion “that organs behave independently of one another, both within and across species.” Organs behaving independently? A somewhat ominous concept, no doubt, but it does explain a lot of the sounds we hear coming from our guts, which can get pretty frightening, especially on chili night.
 

Dog walking is dangerous business

Yes, you did read that right. A lot of strange things can send you to the emergency department. Go ahead and add dog walking onto that list.

Investigators from Johns Hopkins University estimate that over 422,000 adults presented to U.S. emergency departments with leash-dependent dog walking-related injuries between 2001 and 2020.

freestocks/Unsplash

With almost 53% of U.S. households owning at least one dog in 2021-2022 in the wake of the COVID pet boom, this kind of occurrence is becoming more common than you think. The annual number of dog-walking injuries more than quadrupled from 7,300 to 32,000 over the course of the study, and the researchers link that spike to the promotion of dog walking for fitness, along with the boost of ownership itself.

The most common injuries listed in the National Electronic Injury Surveillance System database were finger fracture, traumatic brain injury, and shoulder sprain or strain. These mostly involved falls from being pulled, tripped, or tangled up in the leash while walking. For those aged 65 years and older, traumatic brain injury and hip fracture were the most common.

Women were 50% more likely to sustain a fracture than were men, and dog owners aged 65 and older were three times as likely to fall, twice as likely to get a fracture, and 60% more likely to have brain injury than were younger people. Now, that’s not to say younger people don’t also get hurt. After all, dogs aren’t ageists. The researchers have that data but it’s coming out later.

Meanwhile, the pitfalls involved with just trying to get our daily steps in while letting Muffin do her business have us on the lookout for random squirrels.

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

PHOENIX – When Kathy Givens walked onstage during a plenary session at the annual conference of the American Society for Laser Medicine and Surgery to reflect on her 9-month ordeal being sex trafficked in Texas more than 20 years ago, you could hear a pin drop.

“One of the scariest things about the life of sex trafficking is not knowing who’s going to be on the other side,” said Ms. Givens, who now lives in Houston. “There was some violence. There were some horrible things that happened. But you know what was really scary? When I got out. People may ask, ‘How’s that so? You escaped your trafficker. The past is behind you. Why were you afraid?’ I was afraid because I didn’t know that I had community. I didn’t know that community or that society would care about someone like me.”

Doug Brunk/MDedge News

She said that she found herself immobilized by fear of being shamed in society and labeled a sex trafficking victim, and wondered if she could overcome that fear and if anyone would view her as human again. Once free from her trafficker, she began a “healing journey,” which included getting married, raising four children, and re-enrolling in college with hopes of becoming a social worker. In 2020, she and her husband founded Twelve 11 Partners, an organization committed to supporting human trafficking survivors.

“I was working in the anti-trafficking field helping other survivors ... who have experienced this horrific crime,” she said. “I thought I was on my way.” But one “stain” from her sex trafficking past remained: The name of her trafficker was tattooed on her skin, “a reminder of what I’d gone through.”

Ms. Givens was eventually introduced to Paul M. Friedman, MD, the current ASLMS president and one of the nearly 90 physicians in the United States and Canada who perform tattoo removal free of charge for trafficking survivors as part of the New Beginnings: Tattoo Removal Program, a partnership between the ASLMS and the National Trafficking Sheltered Alliance (NTSA) that was formed in 2022. According to a survey that Dr. Friedman and colleagues presented at the 2022 annual ASLMS conference, an estimated 1 in 2 sex trafficking survivors have branding tattoos, and at least 1,000 survivors a year could benefit from removal of those tattoos.

“To date, 87 physicians in the U.S. and one in Canada have stepped forward to volunteer their services to be part of this program,” Dr. Friedman, who directs the Dermatology and Laser Surgery Center in Houston, said at this year’s meeting. “My goal is to double this number by the next annual conference,” he added, noting that trauma-informed training is part of the program, “to support the survivor experience during the treatment process.”

ASLMS is also working on this issue in partnership with the American Academy of Dermatology (AAD) Ad Hoc Task Force on Dermatological Resources for the Intervention and Prevention of Human Trafficking, which is headed by Boston dermatologist Shadi Kourosh, MD.

“Dermatologists are uniquely positioned to aid in efforts to assist those experiences in trafficking with our training to recognize and diagnose relevant signs on the skin and to assist patients with certain aspects of care and recovery including the treatment of the disease of scars and tattoos,” Dr. Friedman said. “Ultimately, we hope to create a database together to improve recognition of branding tattoos to aid in identifying sex trafficking victims.”

Ms. Givens, who sits on the U.S. Advisory Council on Human Trafficking, said that she was able to truly close the door on her sex trafficking past thanks to the tattoo removal Dr. Friedman performed as part of New Beginnings. “It means the world to me to know that I can now be an advocate for other individuals who have experienced human trafficking,” she told meeting attendees.

“Again, one of the scariest things is not knowing that you have community. I was scared of losing hope, but I’m standing here today. I have all the hope that I need. You have the power to change lives.”

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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

Exposure to four or more CT scans before age 18 years is associated with more than double the risk for certain cancers into early adulthood, data indicate.
 

In a population-based case-control study that included more than 85,000 participants, researchers found a ninefold increased risk of intracranial tumors among children who received four or more CT scans.

The results “indicate that judicious CT usage and radiation-reducing techniques should be advocated,” Yu-Hsuan Joni Shao, PhD, professor of biomedical informatics at Taipei (Taiwan) Medical University, and colleagues wrote.

The study was published in the Canadian Medical Association Journal.
 

Dose-response relationship

The investigators used the National Health Insurance Research Database in Taiwan to identify 7,807 patients under age 25 years with intracranial tumors (grades I-IV), leukemia, non-Hodgkin lymphomas, or Hodgkin lymphomas that had been diagnosed in a 14-year span between the years 2000 and 2013. They matched each case with 10 control participants without cancer by sex, date of birth, and date of entry into the cohort.

Radiation exposure was calculated for each patient according to number and type of CT scans received and an estimated organ-specific cumulative dose based on previously published models. The investigators excluded patients from the analysis if they had a diagnosis of any malignant disease before the study period or if they had any cancer-predisposing conditions, such as Down syndrome (which entails an increased risk of leukemia) or immunodeficiency (which may require multiple CT scans).

Compared with no exposure, exposure to a single pediatric CT scan was not associated with increased cancer risk. Exposure to two to three CT scans, however, was associated with an increased risk for intracranial tumour (adjusted odds ratio, 2.36), but not for leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma.  Exposure to four or more CT scans was associated with increased risk for intracranial tumor (aOR, 9.01), leukemia (aOR, 4.80), and non-Hodgkin lymphoma (aOR, 6.76), but not for Hodgkin lymphoma.

The researchers also found a dose-response relationship. Participants in the top quintile of cumulative brain radiation dose had a significantly higher risk for intracranial tumor, compared with nonexposed participants (aOR, 3.61), although this relationship was not seen with the other cancers.

Age at exposure was also a significant factor. Children exposed to four or more CT scans at or before age 6 years had the highest risk for cancer (aOR, 22.95), followed by the same number of scans in those aged 7-12 years (aOR, 5.69) and those aged 13-18 years (aOR, 3.20).

The authors noted that, although these cancers are uncommon in children, “our work reinforces the importance of radiation protection strategies, addressed by the International Atomic Energy Agency. Unnecessary CT scans should be avoided, and special attention should be paid to patients who require repeated CT scans. Parents and pediatric patients should be well informed on risks and benefits before radiological procedures and encouraged to participate in decision-making around imaging.”
 

True risks underestimated?  

Commenting on the findings, Rebecca Smith-Bindman, MD, a radiologist at the University of California, San Francisco, and an expert on the impact of CT scans on patient outcomes, said that she trusts the authors’ overall findings. But “because of the direction of their biases,” the study design “doesn’t let me accept their conclusion that one CT does not elevate the risk.

“It’s an interesting study that found the risk of brain cancer is more than doubled in children who undergo two or more CT scans, but in many ways, their assumptions will underestimate the true risk,” said Dr. Smith-Bindman, who is a professor of epidemiology and biostatistics at UCSF. She said reasons for this include the fact that the investigators used estimated, rather than actual radiation doses; that their estimates “reflect doses far lower than we have found actually occur in clinical practice”; that they do not differentiate between a low-dose or a high-dose CT; and that that they include a long, 3-year lag during which leukemia can develop after a CT scan.

“They did a lot of really well-done adjustments to ensure that they were not overestimating risk,” said Dr. Smith-Bindman. “They made sure to delete children who had cancer susceptibility syndrome, they included a lag of 3 years, assuming that there could be hidden cancers for up to 3 years after the first imaging study when they might have had a preexisting cancer. These are decisions that ensure that any cancer risk they find is real, but it also means that the risks that are estimated are almost certainly an underestimate of the true risks.”

The study was conducted without external funding. The authors declared no relevant financial relationships. Dr. Smith-Bindman is a cofounder of Alara Imaging, a company focused on collecting and reporting radiation dose information associated with CT.

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