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ECG finding predicts AFib in ibrutinib-treated CLL
NEW YORK – A left atrial abnormality on a pretreatment electrocardiogram (ECG) is a moderately specific and sensitive finding that independently predicts risk for developing atrial fibrillation in chronic lymphocytic leukemia patients starting on ibrutinib, findings from a retrospective cohort study indicate.
ECGs are inexpensive and available in most physician’s offices. Routinely checking for a left atrial abnormality before starting ibrutinib would identify a patient subgroup that would benefit from increased monitoring and allow for proactive intervention strategies to reduce complications should atrial fibrillation develop, Anthony Mato, MD, said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.
Prior studies, including the RESONATE and RESONATE 2 trials, have clearly demonstrated a link between ibrutinib exposure and the development of AFib. Long-term follow-up data suggest an estimated incidence of 9% to 11%.
Dr. Mato and his colleagues used a case-control design within a two-center retrospective cohort study to test the hypothesis that pre-ibrutinib left atrial abnormality, as determined by the ECG, can identify patients at increased risk for AFib during ibrutinib-based therapy.
Of 153 consecutive CLL patients who were treated with ibrutinib 420 mg/day, 11% developed new AFib at a median of 7 months after starting treatment. Discontinuation of ibrutinib because of AFib was low, with less than 2% of the entire cohort discontinuing treatment.
Based on findings in 20 case patients and 24 controls with an available pretreatment ECG, the presence of a left atrial abnormality before ibrutinib therapy was associated with a nine times increased risk of subsequently developing AFib.
“We looked at baseline hypertension, coronary disease, diabetes, age, and sex, and, although hypertension, coronary disease, and age appeared to have some effect, they weren’t as significant as left atrial abnormality” for predicting risk of AFib, Dr. Mato noted.
On multivariate analysis, controlling for hypertension, coronary disease, and age, a left atrial abnormality continued to be a significant predictor of AFib (odds ratio, 6.6).
“We then wanted to make this more practical for clinicians who may potentially perform an ECG to estimate risk,” he said, noting that ECG test characteristics associated with left atrial abnormality were defined: Sensitivity was estimated to be 79%, specificity was 71%, positive and negative likelihood ratios were 2.7 and 0.3, respectively. Positive predictive value was 68%, and negative predictive value was 81%.
The area under the ROC curve for this single predictor was 75%, he said.
The median age of the cohort at CLL diagnosis was 61 years, and the median age at ibrutinib start was 70. Patients had undergone a median of 2 prior lines of therapy, and 87% were treated in the relapsed/refractory setting.
The median follow-up was 17 months, and the median time from CLL diagnosis to the start of ibrutinib was 73 months.
Cardiovascular characteristics prior to treatment included smoking or former smoking in 49%, hypertension in 42%, hyperlipidemia in 39%, diabetes in 17%, coronary artery disease in 12%, and valvular heart disease in 5%.
Controls were matched to cases on baseline characteristics, and only those with no pretreatment history of AFib, a pretreatment ECG, and therapeutic ibrutinib dosing (420 mg/day for at least 4 months) were included.
To minimize bias, all ECGs were reviewed by a cardio-oncologist blinded to clinical outcomes.
The findings need prospective validation, as they are limited by the retrospective study design, lack of balance with respect to cardiovascular characteristics among cases and controls, a small number of atrial fibrillation cases, and variable timing of pre-ibrutinib ECG, he said.
Patients should be educated about the signs and symptoms of AFib. “The development of AFib during ibrutinib treatment should not prevent its continuation. These patients should be managed medically,” he added.
Dr. Mato reported having no disclosures.
NEW YORK – A left atrial abnormality on a pretreatment electrocardiogram (ECG) is a moderately specific and sensitive finding that independently predicts risk for developing atrial fibrillation in chronic lymphocytic leukemia patients starting on ibrutinib, findings from a retrospective cohort study indicate.
ECGs are inexpensive and available in most physician’s offices. Routinely checking for a left atrial abnormality before starting ibrutinib would identify a patient subgroup that would benefit from increased monitoring and allow for proactive intervention strategies to reduce complications should atrial fibrillation develop, Anthony Mato, MD, said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.
Prior studies, including the RESONATE and RESONATE 2 trials, have clearly demonstrated a link between ibrutinib exposure and the development of AFib. Long-term follow-up data suggest an estimated incidence of 9% to 11%.
Dr. Mato and his colleagues used a case-control design within a two-center retrospective cohort study to test the hypothesis that pre-ibrutinib left atrial abnormality, as determined by the ECG, can identify patients at increased risk for AFib during ibrutinib-based therapy.
Of 153 consecutive CLL patients who were treated with ibrutinib 420 mg/day, 11% developed new AFib at a median of 7 months after starting treatment. Discontinuation of ibrutinib because of AFib was low, with less than 2% of the entire cohort discontinuing treatment.
Based on findings in 20 case patients and 24 controls with an available pretreatment ECG, the presence of a left atrial abnormality before ibrutinib therapy was associated with a nine times increased risk of subsequently developing AFib.
“We looked at baseline hypertension, coronary disease, diabetes, age, and sex, and, although hypertension, coronary disease, and age appeared to have some effect, they weren’t as significant as left atrial abnormality” for predicting risk of AFib, Dr. Mato noted.
On multivariate analysis, controlling for hypertension, coronary disease, and age, a left atrial abnormality continued to be a significant predictor of AFib (odds ratio, 6.6).
“We then wanted to make this more practical for clinicians who may potentially perform an ECG to estimate risk,” he said, noting that ECG test characteristics associated with left atrial abnormality were defined: Sensitivity was estimated to be 79%, specificity was 71%, positive and negative likelihood ratios were 2.7 and 0.3, respectively. Positive predictive value was 68%, and negative predictive value was 81%.
The area under the ROC curve for this single predictor was 75%, he said.
The median age of the cohort at CLL diagnosis was 61 years, and the median age at ibrutinib start was 70. Patients had undergone a median of 2 prior lines of therapy, and 87% were treated in the relapsed/refractory setting.
The median follow-up was 17 months, and the median time from CLL diagnosis to the start of ibrutinib was 73 months.
Cardiovascular characteristics prior to treatment included smoking or former smoking in 49%, hypertension in 42%, hyperlipidemia in 39%, diabetes in 17%, coronary artery disease in 12%, and valvular heart disease in 5%.
Controls were matched to cases on baseline characteristics, and only those with no pretreatment history of AFib, a pretreatment ECG, and therapeutic ibrutinib dosing (420 mg/day for at least 4 months) were included.
To minimize bias, all ECGs were reviewed by a cardio-oncologist blinded to clinical outcomes.
The findings need prospective validation, as they are limited by the retrospective study design, lack of balance with respect to cardiovascular characteristics among cases and controls, a small number of atrial fibrillation cases, and variable timing of pre-ibrutinib ECG, he said.
Patients should be educated about the signs and symptoms of AFib. “The development of AFib during ibrutinib treatment should not prevent its continuation. These patients should be managed medically,” he added.
Dr. Mato reported having no disclosures.
NEW YORK – A left atrial abnormality on a pretreatment electrocardiogram (ECG) is a moderately specific and sensitive finding that independently predicts risk for developing atrial fibrillation in chronic lymphocytic leukemia patients starting on ibrutinib, findings from a retrospective cohort study indicate.
ECGs are inexpensive and available in most physician’s offices. Routinely checking for a left atrial abnormality before starting ibrutinib would identify a patient subgroup that would benefit from increased monitoring and allow for proactive intervention strategies to reduce complications should atrial fibrillation develop, Anthony Mato, MD, said at the annual meeting of the International Workshop on Chronic Lymphocytic Leukemia.
Prior studies, including the RESONATE and RESONATE 2 trials, have clearly demonstrated a link between ibrutinib exposure and the development of AFib. Long-term follow-up data suggest an estimated incidence of 9% to 11%.
Dr. Mato and his colleagues used a case-control design within a two-center retrospective cohort study to test the hypothesis that pre-ibrutinib left atrial abnormality, as determined by the ECG, can identify patients at increased risk for AFib during ibrutinib-based therapy.
Of 153 consecutive CLL patients who were treated with ibrutinib 420 mg/day, 11% developed new AFib at a median of 7 months after starting treatment. Discontinuation of ibrutinib because of AFib was low, with less than 2% of the entire cohort discontinuing treatment.
Based on findings in 20 case patients and 24 controls with an available pretreatment ECG, the presence of a left atrial abnormality before ibrutinib therapy was associated with a nine times increased risk of subsequently developing AFib.
“We looked at baseline hypertension, coronary disease, diabetes, age, and sex, and, although hypertension, coronary disease, and age appeared to have some effect, they weren’t as significant as left atrial abnormality” for predicting risk of AFib, Dr. Mato noted.
On multivariate analysis, controlling for hypertension, coronary disease, and age, a left atrial abnormality continued to be a significant predictor of AFib (odds ratio, 6.6).
“We then wanted to make this more practical for clinicians who may potentially perform an ECG to estimate risk,” he said, noting that ECG test characteristics associated with left atrial abnormality were defined: Sensitivity was estimated to be 79%, specificity was 71%, positive and negative likelihood ratios were 2.7 and 0.3, respectively. Positive predictive value was 68%, and negative predictive value was 81%.
The area under the ROC curve for this single predictor was 75%, he said.
The median age of the cohort at CLL diagnosis was 61 years, and the median age at ibrutinib start was 70. Patients had undergone a median of 2 prior lines of therapy, and 87% were treated in the relapsed/refractory setting.
The median follow-up was 17 months, and the median time from CLL diagnosis to the start of ibrutinib was 73 months.
Cardiovascular characteristics prior to treatment included smoking or former smoking in 49%, hypertension in 42%, hyperlipidemia in 39%, diabetes in 17%, coronary artery disease in 12%, and valvular heart disease in 5%.
Controls were matched to cases on baseline characteristics, and only those with no pretreatment history of AFib, a pretreatment ECG, and therapeutic ibrutinib dosing (420 mg/day for at least 4 months) were included.
To minimize bias, all ECGs were reviewed by a cardio-oncologist blinded to clinical outcomes.
The findings need prospective validation, as they are limited by the retrospective study design, lack of balance with respect to cardiovascular characteristics among cases and controls, a small number of atrial fibrillation cases, and variable timing of pre-ibrutinib ECG, he said.
Patients should be educated about the signs and symptoms of AFib. “The development of AFib during ibrutinib treatment should not prevent its continuation. These patients should be managed medically,” he added.
Dr. Mato reported having no disclosures.
AT THE IWCLL MEETING
Key clinical point:
Major finding: Left atrial abnormality as measured using ECG was a significant predictor of AFIB (adjusted odds ratio, 6.6).
Data source: A case-control study of 44 patients within a retrospective cohort.
Disclosures: Dr. Mato reported having no disclosures.
Benefits, safety of dupilumab-steroid combination in adults with AD sustained
Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.
The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).
Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.
In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.
At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).
“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.
Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.
The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.
Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.
The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).
Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.
In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.
At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).
“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.
Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.
The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.
Dupilumab significantly improved symptoms when used in conjunction with topical steroids over one year in a phase III randomized trial of adults with moderate to severe atopic dermatitis (AD) conducted at 161 centers in 14 countries.
The study is “the first large, randomized, double-blinded placebo-controlled study of long-term systemic treatment in patients with moderate-to-severe atopic dermatitis,” wrote Andrew Blauvelt, MD, president of the Oregon Medical Research Center, Portland, and his coauthors. “These results validate the fundamental role for interleukin 4 and interleukin 13 in the pathogenesis of atopic dermatitis,” they added. The findings were published online (Lancet. 2017 May 4. doi: 10.1016/S0140-6736[17]31191-1).
Dupilumab (Dupixent), a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, was approved by the Food and Drug Administration in March for treating moderate-to-severe AD in adults.
In the study, known as LIBERTY AD CHRONOS, 740 patients were enrolled and 1-year data were available for 270 adults who received 300 mg of dupilumab once a week plus topical corticosteroids, 89 patients who received 300 mg of dupilumab every two weeks plus topical corticosteroids, and 264 patients who received a placebo plus topical corticosteroids. The two efficacy endpoints were the percent of patients with Investigator’s Global Assessment (IGA) of 0/1 and a 2-point or higher improvement from baseline and a 75% improvement from baseline on the Eczema Area and Severity Index.
At week 16, significantly more patients who received dupilumab plus topical corticosteroids achieved IGA 0/1 (39% of weekly dupilumab plus topical corticosteroids and 39% of those who received dupilumab every 2 weeks plus topical corticosteroids), compared with 12% of placebo/corticosteroid patients. The percentages of patients in each group who met the EASI-75 endpoint were 64%, 69%, and 23%, respectively (P less than .0001).
“The improvement was sustained over the 52-week treatment period,” and the combination therapy was also associated with improvements in “several other measures of clinical signs and symptoms of atopic dermatitis including pruritus, as well as symptoms of anxiety and depression and health-related quality of life, over the 52-week treatment period,” they wrote.
Adverse events were similar among the groups, with 83%, 88%, and 84% of patients in the weekly dupilumab, biweekly dupilumab, and placebo groups, respectively, reporting at least one adverse event. Nonherpetic skin infections were less common among dupilumab patients than among placebo patients, but conjunctivitis was more common among those on dupilumab (14%-19% vs. 8%). “Dupilumab might be the first targeted immune biologic that is neither immunosuppressive nor associated with increased risk of infection but, rather, restorative of barrier and immune function,” the researchers noted.
The results were limited by several factors including the challenges of determining how much topical medication was actually used by patients across multiple study sites, they wrote. However, the data suggest that “the emerging benefit-to-risk profile in this 52-week study supports the role of dupilumab as a primary targeted biologic therapy for up to 1 year in patients with moderate-to-severe atopic dermatitis who are not controlled with topical medications alone,” they said.
The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Blauvelt and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.
FROM THE LANCET
Key clinical point: One year data on the efficacy and safety of dupilumab, combined with topical steroids, in adults with atopic dermatitis reflected the positive 16-week results, with encouraging safety data.
Major finding: After 16 weeks, 39% of atopic dermatitis patients who received dupilumab in addition to topical steroids met endpoints for improved symptoms, vs. 12% of patients who received topical steroids plus placebo. These benefits were sustained through one year.
Data source: An international phase III randomized trial of adults with moderate to severe atopic dermatitis.
Disclosures: The study was funded by Sanofi and Regeneron Pharmaceuticals. The lead author and coauthors disclosed relationships with companies including Sanofi and Regeneron. Several authors were employees of the two companies.
Infliximab biosimilar noninferior to originator in IBD – NOR-SWITCH
CHICAGO – The biosimilar infliximab CT-P13 is not inferior to the originator infliximab in terms of efficacy, safety, and immunogenicity in the treatment of inflammatory bowel disease (IBD), a phase IV randomized trial showed.
Patient outcomes were not compromised with the use of the biosimilar, and the cost of treatment was much lower, said lead author Kristin K. Jørgensen, MD, PhD, at Digestive Disease Week®.
“Biologics represent a substantial source of IBD expenditure,” said Dr. Jørgensen of Akershus University Hospital, Lørenskog, Norway. “The medication is expensive, patients are treated on a long-term basis, and the incidence of IBD is increasing.”
Biosimilars are biotherapeutic products that are similar in terms of quality, safety, and efficacy to the already licensed reference biologic product. “Use of biosimilars can potentially dramatically decrease costs and may lead to better patient care,” said Dr. Jørgensen. “The patient gets increased access to biologic therapy, and it is easier to intensify dosing if indicated.”
Tumor necrosis factor–inhibitors are commonly used to treat Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, and, while they have altered the treatment paradigm, they are expensive products.
The goal of the NOR-SWITCH was to evaluate switching from originator infliximab to CT-P13, in terms of efficacy, safety, and immunogenicity.
Dr. Jørgensen and her colleagues conducted a randomized phase IV trial that enrolled 482 patients who were randomly assigned to either infliximab originator (n = 241) or CT-P13 (n = 241). The primary endpoint was disease worsening during follow-up.
Of the group, 155 patients (32%) had Crohn’s disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis.
Disease worsening occurred at a similar rate in both groups. In the infliximab originator group, 53 patients (26%) experienced a worsening of their symptoms, compared with 61 patients (30%) in the CT-P13 group. The 95% confidence interval of the adjusted risk difference (−4.4%) was −12.7% to 3.9%, which fell within the prespecified noninferiority margin of 15%.
Therefore, the findings demonstrated that CT-P13 is not inferior to infliximab originator, and the adjusted relative risk of disease worsening for CT-P13 patients was 1.17 (95% CI, 0.82-1.52), compared with the infliximab originator group.
An almost equal number of patients achieved disease remission, 123 patients (61%) in the infliximab originator group and 126 patients (61%) in the CT-P13 group, and the adjusted rate difference was 0.6% (95% CI, –7.5%-8.8%; per-protocol set).
An explorative subgroup analysis that looked at patients with Crohn’s disease and ulcerative colitis showed similar findings between patients treated with either agent.
“Our results support switching from the originator to a biosimilar for nonmedical reasons,” concluded Dr. Jørgensen.
However, she urged caution in generalizing these findings to other biologic agents.
The study was funded by the Norwegian Ministry of Health and Care Services. Dr. Jorgensen reported receiving personal fees from Tillotts, Intercept, and Celltrion. Several coauthors also reported relationships with industry.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – The biosimilar infliximab CT-P13 is not inferior to the originator infliximab in terms of efficacy, safety, and immunogenicity in the treatment of inflammatory bowel disease (IBD), a phase IV randomized trial showed.
Patient outcomes were not compromised with the use of the biosimilar, and the cost of treatment was much lower, said lead author Kristin K. Jørgensen, MD, PhD, at Digestive Disease Week®.
“Biologics represent a substantial source of IBD expenditure,” said Dr. Jørgensen of Akershus University Hospital, Lørenskog, Norway. “The medication is expensive, patients are treated on a long-term basis, and the incidence of IBD is increasing.”
Biosimilars are biotherapeutic products that are similar in terms of quality, safety, and efficacy to the already licensed reference biologic product. “Use of biosimilars can potentially dramatically decrease costs and may lead to better patient care,” said Dr. Jørgensen. “The patient gets increased access to biologic therapy, and it is easier to intensify dosing if indicated.”
Tumor necrosis factor–inhibitors are commonly used to treat Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, and, while they have altered the treatment paradigm, they are expensive products.
The goal of the NOR-SWITCH was to evaluate switching from originator infliximab to CT-P13, in terms of efficacy, safety, and immunogenicity.
Dr. Jørgensen and her colleagues conducted a randomized phase IV trial that enrolled 482 patients who were randomly assigned to either infliximab originator (n = 241) or CT-P13 (n = 241). The primary endpoint was disease worsening during follow-up.
Of the group, 155 patients (32%) had Crohn’s disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis.
Disease worsening occurred at a similar rate in both groups. In the infliximab originator group, 53 patients (26%) experienced a worsening of their symptoms, compared with 61 patients (30%) in the CT-P13 group. The 95% confidence interval of the adjusted risk difference (−4.4%) was −12.7% to 3.9%, which fell within the prespecified noninferiority margin of 15%.
Therefore, the findings demonstrated that CT-P13 is not inferior to infliximab originator, and the adjusted relative risk of disease worsening for CT-P13 patients was 1.17 (95% CI, 0.82-1.52), compared with the infliximab originator group.
An almost equal number of patients achieved disease remission, 123 patients (61%) in the infliximab originator group and 126 patients (61%) in the CT-P13 group, and the adjusted rate difference was 0.6% (95% CI, –7.5%-8.8%; per-protocol set).
An explorative subgroup analysis that looked at patients with Crohn’s disease and ulcerative colitis showed similar findings between patients treated with either agent.
“Our results support switching from the originator to a biosimilar for nonmedical reasons,” concluded Dr. Jørgensen.
However, she urged caution in generalizing these findings to other biologic agents.
The study was funded by the Norwegian Ministry of Health and Care Services. Dr. Jorgensen reported receiving personal fees from Tillotts, Intercept, and Celltrion. Several coauthors also reported relationships with industry.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – The biosimilar infliximab CT-P13 is not inferior to the originator infliximab in terms of efficacy, safety, and immunogenicity in the treatment of inflammatory bowel disease (IBD), a phase IV randomized trial showed.
Patient outcomes were not compromised with the use of the biosimilar, and the cost of treatment was much lower, said lead author Kristin K. Jørgensen, MD, PhD, at Digestive Disease Week®.
“Biologics represent a substantial source of IBD expenditure,” said Dr. Jørgensen of Akershus University Hospital, Lørenskog, Norway. “The medication is expensive, patients are treated on a long-term basis, and the incidence of IBD is increasing.”
Biosimilars are biotherapeutic products that are similar in terms of quality, safety, and efficacy to the already licensed reference biologic product. “Use of biosimilars can potentially dramatically decrease costs and may lead to better patient care,” said Dr. Jørgensen. “The patient gets increased access to biologic therapy, and it is easier to intensify dosing if indicated.”
Tumor necrosis factor–inhibitors are commonly used to treat Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, and, while they have altered the treatment paradigm, they are expensive products.
The goal of the NOR-SWITCH was to evaluate switching from originator infliximab to CT-P13, in terms of efficacy, safety, and immunogenicity.
Dr. Jørgensen and her colleagues conducted a randomized phase IV trial that enrolled 482 patients who were randomly assigned to either infliximab originator (n = 241) or CT-P13 (n = 241). The primary endpoint was disease worsening during follow-up.
Of the group, 155 patients (32%) had Crohn’s disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis.
Disease worsening occurred at a similar rate in both groups. In the infliximab originator group, 53 patients (26%) experienced a worsening of their symptoms, compared with 61 patients (30%) in the CT-P13 group. The 95% confidence interval of the adjusted risk difference (−4.4%) was −12.7% to 3.9%, which fell within the prespecified noninferiority margin of 15%.
Therefore, the findings demonstrated that CT-P13 is not inferior to infliximab originator, and the adjusted relative risk of disease worsening for CT-P13 patients was 1.17 (95% CI, 0.82-1.52), compared with the infliximab originator group.
An almost equal number of patients achieved disease remission, 123 patients (61%) in the infliximab originator group and 126 patients (61%) in the CT-P13 group, and the adjusted rate difference was 0.6% (95% CI, –7.5%-8.8%; per-protocol set).
An explorative subgroup analysis that looked at patients with Crohn’s disease and ulcerative colitis showed similar findings between patients treated with either agent.
“Our results support switching from the originator to a biosimilar for nonmedical reasons,” concluded Dr. Jørgensen.
However, she urged caution in generalizing these findings to other biologic agents.
The study was funded by the Norwegian Ministry of Health and Care Services. Dr. Jorgensen reported receiving personal fees from Tillotts, Intercept, and Celltrion. Several coauthors also reported relationships with industry.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
AT DDW
Key clinical point: An infliximab biosimilar was not inferior to the originator in terms of efficacy, safety, and immunogenicity in the treatment of inflammatory bowel disease (IBD).
Major finding: In the infliximab originator group, 53 patients (26%) experienced disease worsening, vs. 61 patients (30%) in the CT-P13 group, which fell within the prespecified noninferiority margin of 15%.
Data source: A phase IV randomized trial that included 482 patients with inflammatory bowel disease.
Disclosures: The study was funded by the Norwegian Ministry of Health and Care Services. Dr. Jorgensen reported receiving personal fees from Tillotts, Intercept, and Celltrion. Several coauthors also reported relationships with industry.
Experts bust common sports medicine myths
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44). 
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44).
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
SAN DIEGO – Is it okay for pregnant women to attend CrossFit classes? Are patients who run for fun at increased risk for osteoarthritis? Does stretching before exercise provide any benefits to athletes?
Experts discussed these topics during a session titled “Mythbusters in sports medicine” at the annual meeting of the American Medical Society for Sports Medicine.
Does exercise negatively impact pregnancy?
The idea that strenuous exercise during pregnancy can harm a baby’s health is a myth, according to Elizabeth A. Joy, MD.
“Women having healthy, uncomplicated pregnancies should be encouraged to be physically active throughout pregnancy, with a goal of achieving 150 minutes per week of moderate-intensity activity,” she said. “Fit pregnant women who were habitually performing high-intensity exercise before pregnancy can continue to do so during pregnancy, assuming an otherwise healthy, uncomplicated pregnancy.”
Results from more than 600 studies in the medical literature indicate that exercise during pregnancy is safe for moms and babies, noted Dr. Joy, medical director for community health and food and nutrition at Intermountain Healthcare in Salt Lake City, Utah.
In fact, the 2008 Physical Activity Guidelines for Americans state that pregnant women who habitually engage in vigorous-intensity aerobic activity or who are highly active “can continue physical activity during pregnancy and the postpartum period, provided that they remain healthy and discuss with their health care provider how and when activity should be adjusted over time.”
Such advice wasn’t always supported by the medical profession. In fact, 1985 guidelines from the American College of Obstetricians and Gynecologists recommended that women limit exercise to no more than 15 minutes at a time during pregnancy and keep their maternal heart rate less than 140 beats per minute. ACOG also discouraged previously sedentary women from beginning an exercise program during pregnancy.
“Sadly, women are still getting this advice,” said Dr. Joy, who is also president of the American College of Sports Medicine. According to the 2005-2010 National Ambulatory Medical Care Survey, only 18% of pregnant women reported receiving counseling to be physically active during their pregnancies (Matern Child Health J. 2014 Sep;18[7]:1610-18). “That is just unacceptable,” she said.
In a prospective study of the association between vigorous physical activity during pregnancy and length of gestation and birth weight, researchers evaluated 1,647 births among primiparous women (Matern Child Health J. 2012 Jul;16[5]:1031-44).
They conducted telephone interviews with the women between 7-20 weeks gestation and assigned metabolic equivalent of task values to self-reported levels of physical activity. Of the 1,647 births, 7% were preterm.
Slightly more than one-third of the women (35%) performed first-trimester vigorous physical activity. The average total vigorous activity reported was 76 minutes per week, 38% of which was vigorous recreational activity.
Women who performed first-trimester vigorous recreational physical activity tended to have lower odds of preterm birth. They also tended to have lighter-weight babies, but this did not reach statistical significance (P = .08). The authors concluded that first-trimester vigorous physical activity “does not appear to be detrimental to the timing of birth or birth weight.”
In a separate analysis, researchers evaluated acute fetal responses to individually prescribed exercise according to existing physical activity guidelines in active and inactive pregnant women (Obstet Gynecol. 2012 Mar;119[3]:603-10).
Of the 45 study participants, 15 were classified as nonexercisers, 15 were regularly active, and 15 were highly active. The women underwent treadmill assessment between 28 weeks and 33 weeks, while fetal assessment included umbilical artery Doppler, fetal heart tracing and rate, and biophysical profile at rest and immediately post exercise.
The researchers observed no differences between the groups in mode of delivery, birth weight, and Apgar scores. During vigorous-intensity exercise, all umbilical artery indices showed decreases post exercise.
“Although statistically significant, this decrease is likely not clinically significant,” the researchers wrote. “We did not identify any adverse acute fetal responses to current exercise recommendations.” They went on to conclude that the potential health benefits of exercise “are too great for [physicians] to miss the opportunity to effectively counsel pregnant women about this important heath-enhancing behavior.”
In a more recent randomized study, Swedish researchers evaluated the efficacy of moderate-to-vigorous resistance exercise in 92 pregnant women (Acta Obstet Gynecol Scand. 2015 Jan; 94[1]:35-42).
The intervention group received supervised resistance exercise twice per week at moderate-to-vigorous intensity between 14-25 weeks of their pregnancy, while the control group received a generalized home exercise program. Outcome measures included health-related quality of life, physical strength, pain, weight, blood pressure, functional status, activity level, and perinatal data.
The researchers found no significant differences between the two groups and concluded that “supervised regular, moderate-to-vigorous resistance exercise performed twice per week does not adversely impact childbirth outcome, pain, or blood pressure.”
Despite all that’s known about exercise during pregnancy, a few practice and research gaps remain.
For one, Dr. Joy said, the relationship between performing physically demanding work during pregnancy in combination with moderate-to-vigorous exercise remains largely unknown.
“Even within health care, you have residents, nurses, and others working in hospitals,” she said. “That’s demanding work, but we don’t know whether or not moderate-to-vigorous exercise in combination with that kind of work is safe. Also, although women tend to thermoregulate better during pregnancy, we still don’t fully understand the impact of elevated core body temperature, which may occur with regularly performed vigorous-intensity exercise over the course of pregnancy.”
Does running cause knee OA?
During another talk at the meeting, William O. Roberts, MD, characterized the notion that running causes knee osteoarthritis as largely a myth for recreational runners. However, elite runners and athletes who participate in other sports may face an increased risk of developing the condition.
Well-established risk factors for knee OA include post–joint injury proteases and cytokines and injury load stress on articular cartilage. “Other risk factors include overweight and obesity, a family history of OA, exercise, heavy work that involved squatting and kneeling, and being female,” said Dr. Roberts, professor of family medicine and community health at the University of Minnesota, Minneapolis.
He discussed three articles on the topic drawn from medical literature. One was a retrospective cross-sectional analysis of 2,637 Osteoarthritis Initiative participants, 45-79 years of age, who had knee-specific pain or knee x-ray data 4 years into the 10-year–long study (Arthritis Care Res. 2017 Feb;69[2]:183-91).
More than half of the participants (56%) were female, their mean body mass index was 28.5 kg/m2, only 20% reported more than 2,000 bouts of running during their lifetime, and about 5% had run competitively.
Adjusted odds ratios of pain, radiographic OA, and symptomatic OA for those prior runners and current runners, compared with those who never ran, were 0.82 and 0.76 (P for trend = .02), 0.98 and 0.91 (P for trend = .05), and 0.88 and 0.71 (P for trend = .03), respectively.
The authors concluded that running does not appear to be detrimental to the knees, and the strength of recommendation taxonomy was rated as 2B.
In a separate analysis, researchers performed a systematic review and meta-analysis of 11 cohort (6 retrospective) and 4 case-control studies related to running and knee arthritis (Am J Sports Med. 2016 May;45[6]:1447-57). The mean ages of subjects at outcome assessment ranged from 27 years to 69 years, and the sample size ranged from 15 to 1,279 participants. The four case control studies assessed exposure by mailed questionnaire or by personal interview.
The meta-analysis suggests that runners have a 50% reduced odds of requiring a total knee replacement because of OA.
“It contradicts some previous studies, and there were confounders,” Dr. Roberts said of the analysis. “The one that I noticed is that people would delay surgery to keep running. That’s what I find in my practice.”
The researchers were unable to link running to knee OA development. Moderate- to low-quality evidence suggests a positive association with OA diagnosis but a negative association with requirement for a total knee replacement.
Based on published evidence, they concluded there is no clear advice to give regarding the potential effect of running on musculoskeletal health and rated the strength of evidence as 1A.
A third study Dr. Roberts discussed investigated the association between specific sports participation and knee OA (J Athl Train. 2015 Jan. 9. doi: 10.4085/1062-6050-50.2.08). After locating nearly 18,000 articles on the topic, the researchers limited their meta-analysis to 17 published studies.
They found that the overall risk of knee OA prevalence in sports participants was 7.7%, compared with 7.3% among nonexposed controls (odds ratio, 0.9). However, risks for knee OA were elevated among those who participated in the following sports: soccer (OR, 3.5), elite long-distance running (OR, 3.3), competitive weightlifting (OR, 6.9), and wrestling (OR, 3.8). The researchers concluded that athletes who participate in those sports “should be targeted for risk-reduction strategies.”
“So, does running cause knee OA? It depends,” said Dr. Roberts, who is also medical director of Twin Cities in Motion. “There is a potential risk to high-volume, high-intensity, and long-distance runners, but there does not appear to be a risk in fitness or recreational runners. Of course, you can’t erase your genetics.”
He called for more research on the topic, including prospective longitudinal outcomes studies, those that study the role of genetics/epigenetics in runners and nonrunners who develop knee OA and those focused on the knee joint “chemical environment,” referring to recent work that suggests that running appears to decrease knee intra-articular proinflammatory cytokine concentration (Eur J Appl Physiol. 2016 Dec;116[11-12]:2305-14).
“It’s okay to run for fitness, because the health benefits far outweigh the risk of knee OA,” Dr. Roberts said. “If you run hard and long, it could be a problem. We probably should be screening for neuromuscular control to reduce anterior cruciate ligament disruption.”
Does it help to stretch before exercise?
Stretching before engaging in exercise is a common practice often recommended by coaches and clinicians – but it appears to have no role in preventing injuries during exercise itself.
Several decades ago, investigators subscribed to muscle spasm theory, which held that unaccustomed exercise caused muscle spasms.
“The thought was that muscle spasms impeded blood flow to the muscle, causing ischemic pain and further spasm,” Valerie E. Cothran, MD, said during a presentation at the meeting. “Stretching the muscle was thought to restore blood flow to the muscle and interrupt the pain-spasm-pain cycle. This theory has been discredited for 40 years, but the practice of stretching before exercise persists.”
According to Dr. Cothran, of the department of family and community medicine at the University of Maryland, Baltimore, a limited number of randomized, controlled trials exist on the topic – and many are fraught with limitations, such as the evaluation of multiple stretching methods and variable types of sports activities and the inclusion of multiple cointerventions.
One systematic review evaluated 361 randomized, controlled trials and cohort studies of interventions that included stretching and that appeared in the medical literature from 1966 to 2002 (Med Sci Sports Exerc. 2004 Mar;36[3]:371-8). Studies with no controls were excluded from the analysis, as were those in which stretching could not be assessed independently or those that did not include people engaged in sports or fitness activities.
The researchers determined that stretching was not significantly associated with a reduction in total injuries (OR, 0.93). “There is not sufficient evidence to endorse or discontinue routine stretching before or after exercise to prevent injury among competitive or recreational athletes,” they concluded.
The following year, Lawrence Hart, MBBch, of McMaster University, Hamilton, Ont., assessed the same set of data but eliminated some of the confounding factors of the previous analysis, including studies that had limited statistical power (Clin J Sport Med. 2005 Mar;15[2]:113). The final meta-analysis included six studies.
Dr. Hart found that neither stretching of specific leg-muscle groups or multiple muscle groups led to a reduction in total injuries, such as shin splints, tibial stress reaction, or sprains/strains (OR, 0.93). In addition, reduction in injuries was not significantly greater for stretching of specific muscles or multiple muscle groups (OR, 0.80, and OR, 0.96, respectively). “Limited evidence showed stretching had no effects on injuries,” he concluded.
A more recent systematic review analyzed the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury (Res Sports Med. 2008;16[3]:213-31). The researchers reviewed 364 studies published after 1990 but before 2008, and they included seven in the final analysis: four randomized, controlled trials and three controlled trials.
All four randomized, controlled trials concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three controlled trials concluded that static stretching reduced the incidence of exercise-related injury. In addition, three of the seven studies reported significant reductions in musculotendinous and ligament injuries following a static stretching protocol.
“There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates,” the researchers concluded. “There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.”
The final study Dr. Cothran discussed was a systematic review of two randomized, controlled trials and two prospective cohort studies on the effect of stretching in sports injury prevention that appeared in the literature between 1998 and 2008 (J Comm Health Sci. 2008;3[1]:51-8).
One cohort study found that stretching reduced the incidence of exercise-related injuries, while two randomized, controlled trials and one cohort study found that stretching did not produce a practical reduction on the occurrence of injuries. The researchers concluded that stretching exercises “do not give a practical, useful reduction in the risk of injuries.”
Some studies have demonstrated that explosive athletic performance such as sprinting may be compromised by acute stretching, noted Dr. Cothran, who is also program director of the primary care sports medicine fellowship at the University of Maryland, Baltimore. Current practice and research gaps include few recent randomized, controlled trials; few studies isolating stretching alone; and few that compare the different forms of stretching, such as dynamic and static stretching, she added.
“There is moderate to strong evidence that routine stretching before exercise will not reduce injury rates,” she concluded. “There is evidence that stretching before exercise may negatively affect performance. Flexibility training can be beneficial but should take place at alternative times and not before exercise.”
Dr. Joy disclosed that she receives funding from Savvysherpa and Dexcom for a project on the prevention of gestational diabetes. Dr. Roberts and Dr. Cothran reported having no financial disclosures.
AKI doubles risk of death for those with acute pancreatitis
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
[email protected]
On Twitter @alz_gal
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
[email protected]
On Twitter @alz_gal
CHICAGO – Acute kidney injury (AKI) doubles the risk of death among patients hospitalized for acute pancreatitis, Kalpit Devani, MD, reported at the annual Digestive Disease Week®.
This severe complication of acute pancreatitis also significantly increases the length of stay and drives up hospital costs, said Dr. Devani of East Tennessee State University, Johnson City. Fortunately, although the risks associated with it remain high, death from AKI in the setting of acute pancreatitis has decreased significantly, from a high of 17% in 2002 to 6.4% in 2012, Dr. Devani determined in his database review.
“Increasing awareness and prompt diagnosis of AKI could be the reason for the increasing trend of prevalence of AKI in acute pancreatitis patients,” he said in an interview. “Decreasing mortality can be related to adherence to recent advances in the management approach of acute pancreatitis, such as early (within 24 hours) and aggressive intravenous hydration and early enteral feeding.”
Dr. Devani examined these trends in data extracted from the National Inpatient Sample, 2002-2012. During that 10-year period, almost 3.5 million adults were hospitalized for acute pancreatitis. These patients were a mean of 53 years old, and half were women. Their mean length of stay was just over 5 days, at a mean cost of about $12,000. Of these, 273,687 (7.9%) also developed AKI.
There were some significant differences between those who did and did not develop AKI. AKI patients were significantly older (61 vs. 53 years), and less likely to be women (43% vs. 51%). They had a higher Charlson Comorbidity Index score (1.49 vs. 0.84). They were also significantly more likely to develop a number of complications, including systemic inflammatory response syndrome (2% vs. 0.4%), septic shock (6% vs. 0.3%), sepsis (8.7% vs. 1.4%), acute respiratory failure (18% vs. 2%), and electrolyte disorder (72% vs. 30%).
Not surprisingly, their length of stay was significantly longer (10 vs. 5 days), as was hospitalization cost ($25,923 vs. $10,889). Mortality was much higher, at almost 9% vs. 0.7%.
In a propensity matching analysis, Dr. Devani matched 53,000 pairs of acute pancreatitis patients with and without AKI. This determined that those with AKI faced a doubling in the risk of in-hospital mortality.
He also examined temporal trends with regard to the complication. The rate of diagnosed AKI in hospitalized acute pancreatitis cases rose dramatically, from 4% in 2002 to 11.6% in 2012. However, mortality in acute pancreatitis patients decreased among both those with AKI (17%-6%) and those without (1%-0.4%).
The mean length of stay in patients with AKI and pancreatitis likewise fell, from 14.8 to 8.6 days. Not surprisingly, total hospitalization cost for these patients fell as well ($42,975-$20,716).
Among pancreatitis patients without AKI, length of stay and costs declined, although not as dramatically as they did among AKI patients (6-5 days; $13,654-$10,895).
Dr. Devani had no financial disclosures.
[email protected]
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: Mortality among those with AKI was 9% vs. 0.7% among those without. After controlling for confounders, the risk of death was doubled.
Data source: A 10-year National Inpatient Sample database review comprising 3.5 million patients with pancreatitis.
Disclosures: Dr. Devani had no financial disclosures.
Bariatric patients can conquer obesity, but few achieve BMI < 25
Around one-quarter of obese individuals who undergo Roux-en-Y gastric bypass had sustained, long-term remission of obesity, but far fewer achieved body mass index of under 25 kg/m2 or maintained it over 5 years, new research suggests.
Researchers reported on the outcomes of a retrospective cohort study of 219 patients who underwent Roux-en-Y gastric bypass surgery at a single center between 2008 and 2010 and were followed for up to 7 years after the procedure.
Only 16.9% of female patients achieved a BMI of under 25 kg/m2 – during the study period, and only 2.7% reached this BMI by year 2 and sustained it at least to year 5 of follow-up.
Two males in the study achieved BMI of under 25 during follow-up. One was recorded as having maintained this weight at year 1 and the other at year 4, but no further measurements were available for either.
“Given the low number of patients achieving BMI of less than 25 kg/m2, we also wanted to focus on another important clinical goal of obesity remission (BMI less than 30),” wrote Corey J. Lager, MD, of the University of Michigan, Brehm Center for Diabetes, Ann Arbor, and his coauthors. “Taking into account that the mean BMI prior to surgery in our cohort was 47.1 kg/m2, this target is associated with significant estimated health benefits and likely brings a mortality benefit for patients undergoing gastric bypass.”
The authors said that a conservative estimate of the probability of achieving and sustaining BMI 25 or less after Roux-en-Y gastric bypass was just 2.3%. However, they offered a more liberal estimate – based on the number of patients who were at BMI 25 or under at the last available data point – of 6.8%.
Achieving weight loss to a BMI less than 30 was significantly influenced by age. The group who achieved this weight were on average 3 years younger at baseline than those who did not.
Similarly, initial BMI played a role in outcomes. The women who achieved a BMI below 30 had an initial mean BMI of 43.5, compared with 50.4 in the women who did not achieve this weight (P less than .0001). In males, the mean baseline BMI in those who got their weight below 30 was 44.6, compared with 48.1 in those who did not (P = .18).
Roux-en-Y gastric bypass was also associated with significant and sustained decreases in both systolic and diastolic blood pressure that was similar for both sexes. The maximum mean decrease of 14 ± 7 mm Hg was achieved at 1 year after surgery, and, at 5 years, the mean decrease was 11 ± 3 mm Hg.
The authors commented that, despite “excellent” weight loss being achieved by a majority of patients, the findings show the challenge of weight loss and maintenance in patients with a very high BMI. However, they also pointed to the encouragingly low rates of significant weight regain and the fact that fewer than 1% of patients returned to a weight greater than their preoperative weight. Higher preoperative BMI was correlated with greater weight loss but also negatively correlated with achieving BMI under 30.
The authors concluded with two takeaway messages. First, realistic goals should be set for patients undergoing gastric bypass surgery, with an emphasis on remission of obesity and with a reduced expectation of achievement of BMI under 25 over the long run. In addition, because the higher the initial BMI, the less likely that weight loss will not be maintained, “we should also carefully examine the option of pursuing surgery at lower BMI cutoffs, at which point patients have a greater likelihood of obesity remission.”
The study was supported by the University of Michigan Health System, the National Institutes of Health, and the Nutrition Obesity Research Centers. One author declared grant support and advisory positions with pharmaceutical companies and intellectual property unrelated to the study. Another author is an investigator on a sponsored clinical study. No other conflicts of interest were declared.
Around one-quarter of obese individuals who undergo Roux-en-Y gastric bypass had sustained, long-term remission of obesity, but far fewer achieved body mass index of under 25 kg/m2 or maintained it over 5 years, new research suggests.
Researchers reported on the outcomes of a retrospective cohort study of 219 patients who underwent Roux-en-Y gastric bypass surgery at a single center between 2008 and 2010 and were followed for up to 7 years after the procedure.
Only 16.9% of female patients achieved a BMI of under 25 kg/m2 – during the study period, and only 2.7% reached this BMI by year 2 and sustained it at least to year 5 of follow-up.
Two males in the study achieved BMI of under 25 during follow-up. One was recorded as having maintained this weight at year 1 and the other at year 4, but no further measurements were available for either.
“Given the low number of patients achieving BMI of less than 25 kg/m2, we also wanted to focus on another important clinical goal of obesity remission (BMI less than 30),” wrote Corey J. Lager, MD, of the University of Michigan, Brehm Center for Diabetes, Ann Arbor, and his coauthors. “Taking into account that the mean BMI prior to surgery in our cohort was 47.1 kg/m2, this target is associated with significant estimated health benefits and likely brings a mortality benefit for patients undergoing gastric bypass.”
The authors said that a conservative estimate of the probability of achieving and sustaining BMI 25 or less after Roux-en-Y gastric bypass was just 2.3%. However, they offered a more liberal estimate – based on the number of patients who were at BMI 25 or under at the last available data point – of 6.8%.
Achieving weight loss to a BMI less than 30 was significantly influenced by age. The group who achieved this weight were on average 3 years younger at baseline than those who did not.
Similarly, initial BMI played a role in outcomes. The women who achieved a BMI below 30 had an initial mean BMI of 43.5, compared with 50.4 in the women who did not achieve this weight (P less than .0001). In males, the mean baseline BMI in those who got their weight below 30 was 44.6, compared with 48.1 in those who did not (P = .18).
Roux-en-Y gastric bypass was also associated with significant and sustained decreases in both systolic and diastolic blood pressure that was similar for both sexes. The maximum mean decrease of 14 ± 7 mm Hg was achieved at 1 year after surgery, and, at 5 years, the mean decrease was 11 ± 3 mm Hg.
The authors commented that, despite “excellent” weight loss being achieved by a majority of patients, the findings show the challenge of weight loss and maintenance in patients with a very high BMI. However, they also pointed to the encouragingly low rates of significant weight regain and the fact that fewer than 1% of patients returned to a weight greater than their preoperative weight. Higher preoperative BMI was correlated with greater weight loss but also negatively correlated with achieving BMI under 30.
The authors concluded with two takeaway messages. First, realistic goals should be set for patients undergoing gastric bypass surgery, with an emphasis on remission of obesity and with a reduced expectation of achievement of BMI under 25 over the long run. In addition, because the higher the initial BMI, the less likely that weight loss will not be maintained, “we should also carefully examine the option of pursuing surgery at lower BMI cutoffs, at which point patients have a greater likelihood of obesity remission.”
The study was supported by the University of Michigan Health System, the National Institutes of Health, and the Nutrition Obesity Research Centers. One author declared grant support and advisory positions with pharmaceutical companies and intellectual property unrelated to the study. Another author is an investigator on a sponsored clinical study. No other conflicts of interest were declared.
Around one-quarter of obese individuals who undergo Roux-en-Y gastric bypass had sustained, long-term remission of obesity, but far fewer achieved body mass index of under 25 kg/m2 or maintained it over 5 years, new research suggests.
Researchers reported on the outcomes of a retrospective cohort study of 219 patients who underwent Roux-en-Y gastric bypass surgery at a single center between 2008 and 2010 and were followed for up to 7 years after the procedure.
Only 16.9% of female patients achieved a BMI of under 25 kg/m2 – during the study period, and only 2.7% reached this BMI by year 2 and sustained it at least to year 5 of follow-up.
Two males in the study achieved BMI of under 25 during follow-up. One was recorded as having maintained this weight at year 1 and the other at year 4, but no further measurements were available for either.
“Given the low number of patients achieving BMI of less than 25 kg/m2, we also wanted to focus on another important clinical goal of obesity remission (BMI less than 30),” wrote Corey J. Lager, MD, of the University of Michigan, Brehm Center for Diabetes, Ann Arbor, and his coauthors. “Taking into account that the mean BMI prior to surgery in our cohort was 47.1 kg/m2, this target is associated with significant estimated health benefits and likely brings a mortality benefit for patients undergoing gastric bypass.”
The authors said that a conservative estimate of the probability of achieving and sustaining BMI 25 or less after Roux-en-Y gastric bypass was just 2.3%. However, they offered a more liberal estimate – based on the number of patients who were at BMI 25 or under at the last available data point – of 6.8%.
Achieving weight loss to a BMI less than 30 was significantly influenced by age. The group who achieved this weight were on average 3 years younger at baseline than those who did not.
Similarly, initial BMI played a role in outcomes. The women who achieved a BMI below 30 had an initial mean BMI of 43.5, compared with 50.4 in the women who did not achieve this weight (P less than .0001). In males, the mean baseline BMI in those who got their weight below 30 was 44.6, compared with 48.1 in those who did not (P = .18).
Roux-en-Y gastric bypass was also associated with significant and sustained decreases in both systolic and diastolic blood pressure that was similar for both sexes. The maximum mean decrease of 14 ± 7 mm Hg was achieved at 1 year after surgery, and, at 5 years, the mean decrease was 11 ± 3 mm Hg.
The authors commented that, despite “excellent” weight loss being achieved by a majority of patients, the findings show the challenge of weight loss and maintenance in patients with a very high BMI. However, they also pointed to the encouragingly low rates of significant weight regain and the fact that fewer than 1% of patients returned to a weight greater than their preoperative weight. Higher preoperative BMI was correlated with greater weight loss but also negatively correlated with achieving BMI under 30.
The authors concluded with two takeaway messages. First, realistic goals should be set for patients undergoing gastric bypass surgery, with an emphasis on remission of obesity and with a reduced expectation of achievement of BMI under 25 over the long run. In addition, because the higher the initial BMI, the less likely that weight loss will not be maintained, “we should also carefully examine the option of pursuing surgery at lower BMI cutoffs, at which point patients have a greater likelihood of obesity remission.”
The study was supported by the University of Michigan Health System, the National Institutes of Health, and the Nutrition Obesity Research Centers. One author declared grant support and advisory positions with pharmaceutical companies and intellectual property unrelated to the study. Another author is an investigator on a sponsored clinical study. No other conflicts of interest were declared.
FROM OBESITY SURGERY
Key clinical point: Roux-en-Y gastric bypass is associated with sustained, long-term remission of obesity in around one-quarter of patients.
Major finding: Nearly one-quarter of patients who underwent Roux-en-Y gastric bypass achieved a BMI below 30 kg/m2 that was sustained at their last follow-up, but healthy weight was sustained at 5 years’ follow-up in far fewer patients.
Data source: Retrospective cohort study of 219 patients.
Disclosures: The study was supported by the University of Michigan Health System, the National Institutes of Health, and the Nutrition Obesity Research Centers. One author declared grant support and advisory positions with pharmaceutical companies and intellectual property unrelated to the study. Another author is an investigator on a sponsored clinical study. No other conflicts of interest were declared.
Seeing a doctor reduces readmission risk in schizophrenia patients
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
SAN DIEGO – Readmission rates after discharge for patients with schizophrenia are notoriously high, with approximately a quarter of U.S. schizophrenia patients readmitted within 3 months, according to Paul A. Kurdyak, MD, PhD.
In Ontario, Canada, readmission rates for people with schizophrenia are 12.5% within 30 days of discharge. Paradoxically, however, these same patients receive less follow-up than people hospitalized for other psychiatric disorders, Dr. Kurdyak of the Institute for Clinical Evaluative Sciences in Toronto reported at the annual meeting of the American Psychiatric Association.
To explore the relationship between discharge, follow-up, and subsequent readmission in this population, he assessed the impact of physician follow-up in the month after discharge on readmission rates for schizophrenia patients, noting a lack of published evidence on whether or how it helps. “We try and use readmission as a general performance indicator, and we try and use postdischarge follow-up as a general indicator, but there was no evidence to determine whether seeing a physician following discharge has an impact on anything,” Dr. Kurdyak said.
He and his colleagues tracked primary care and outpatient psychiatric visits in the first 30 days after discharge for about 20,000 people who had been hospitalized with schizophrenia in Ontario. “We chose 30 days because we knew the rate of follow-up within 7 days was just so low,” he said.
He said more than one in three of these patients went more than 30 days without seeing any physician at all.
Schizophrenia patients “are individuals with really high needs, whose average length of stay is about 2 weeks,” he said. “It’s hard to stabilize somebody in 2 weeks, so to have so many of them drop off a cliff [after discharge] is not great.”
Another finding was that the patients who saw any doctor – whether their primary care physician or psychiatrist – saw reduced rates of readmission at 30-210 days after discharge.
Where the benefit of seeing a physician was seen in sharpest relief was among the patients deemed, by use of a validated scoring system, to be at highest risk for readmission. These patients, who made up two-thirds of the cohort, saw a 15% reduction in readmission if they’d had a visit with either a primary care physician or psychiatrist and a 19% reduction if they’d seen both types of physician relative to patients who had no physician follow-up post discharge.
“In the high-risk group, you see a very clear separation between those who saw no physician and those who saw any physician,” Dr. Kurdyak said.
Some of the limitations of the study included the fact that little was known about the quality of the follow-up physician visits or about clinical collaboration, the causes for lack of follow-up were not clear, and follow-up by nonphysician health personnel was not captured.
Nonetheless, Dr. Kurdyak said, “the moral of the story is [that] seeing a physician really differentiates from seeing no physician statistically and clinically.”
In Canada, he noted, “we like to feel comfortable with the idea of universal health care, but, when we take a closer look, we often see real inequities and disparities despite universal health care. I think this is one of these situations where, if readmission is an indicator of need, our ability to provide services to those in the greatest need falls short of the ideal.”
Dr. Kurdyak disclosed no conflicts of interest relevant to his research.
AT APA
Key clinical point:
Major finding: Patients at highest risk of readmission saw a 15% reduction in readmission after 30 days if they’d seen a primary care doctor or psychiatrist, compared with those who’d seen neither.
Data source: Records from about 20,000 schizophrenia patients hospitalized in Ontario in 2012, identified in government databases.
Disclosures: The study was conducted at an institute receiving most of its support from the Ontario government.
Parkinsonian symptoms at diagnosis raise synucleinopathy mortality risk
The elevated risk of death for patients with clinically diagnosed synucleinopathies and symptoms of parkinsonism is highest for those with multiple system atrophy with predominant parkinsonism (MSA-p), followed by dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and Parkinson’s disease (PD), according to Rodolfo Savica, MD, PhD, and his associates.
The investigators compared 461 patients who had onset of a clinically presumed synucleinopathy manifesting as parkinsonism from 1991 to 2010 with 452 age- and sex-matched referent participants from the general population who were free of parkinsonism and tremor of any type in the year of onset of the other patients’ synucleinopathies. Of the 461 patients with the presumed synucleinopathies, 316 (68.6%) died during follow-up and 311 had a known cause of death (98.4%). Of the 452 referent participants, 220 (48.7%) died during follow-up and 216 had a known cause of death (98.2%). The highest risk of death was among patients with MSA-p (hazard ratio, 10.51) when compared with referent participants. The remaining patients also had elevated risk of death: DLB (HR, 3.94), PDD (HR, 3.86), and PD (HR, 1.75).
Neurodegenerative disease was the most frequent cause of death among patients for all synucleinopathies (31.5%) and in PD alone (25.6%), and cardiovascular events were the second most common cause of death (15.7%). Among the referent participants, cardiovascular events were the most common cause of death (25.5%).
The results were consistent with the causes of death observed among patients with DLB, PDD, and MSA-p; however, the researchers said the sample size was too limited to observe a sufficient number of events. They also noted that there was no significant interaction with sex and age in predicting survival rates for any type of synucleinopathy.
“Our findings contribute important new evidence about the natural history and survival of people affected by synucleinopathies of various types,” the researchers concluded. “Our results may be helpful to guide clinicians counseling patients and caregivers.”
Find the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2017.0603).
The elevated risk of death for patients with clinically diagnosed synucleinopathies and symptoms of parkinsonism is highest for those with multiple system atrophy with predominant parkinsonism (MSA-p), followed by dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and Parkinson’s disease (PD), according to Rodolfo Savica, MD, PhD, and his associates.
The investigators compared 461 patients who had onset of a clinically presumed synucleinopathy manifesting as parkinsonism from 1991 to 2010 with 452 age- and sex-matched referent participants from the general population who were free of parkinsonism and tremor of any type in the year of onset of the other patients’ synucleinopathies. Of the 461 patients with the presumed synucleinopathies, 316 (68.6%) died during follow-up and 311 had a known cause of death (98.4%). Of the 452 referent participants, 220 (48.7%) died during follow-up and 216 had a known cause of death (98.2%). The highest risk of death was among patients with MSA-p (hazard ratio, 10.51) when compared with referent participants. The remaining patients also had elevated risk of death: DLB (HR, 3.94), PDD (HR, 3.86), and PD (HR, 1.75).
Neurodegenerative disease was the most frequent cause of death among patients for all synucleinopathies (31.5%) and in PD alone (25.6%), and cardiovascular events were the second most common cause of death (15.7%). Among the referent participants, cardiovascular events were the most common cause of death (25.5%).
The results were consistent with the causes of death observed among patients with DLB, PDD, and MSA-p; however, the researchers said the sample size was too limited to observe a sufficient number of events. They also noted that there was no significant interaction with sex and age in predicting survival rates for any type of synucleinopathy.
“Our findings contribute important new evidence about the natural history and survival of people affected by synucleinopathies of various types,” the researchers concluded. “Our results may be helpful to guide clinicians counseling patients and caregivers.”
Find the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2017.0603).
The elevated risk of death for patients with clinically diagnosed synucleinopathies and symptoms of parkinsonism is highest for those with multiple system atrophy with predominant parkinsonism (MSA-p), followed by dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and Parkinson’s disease (PD), according to Rodolfo Savica, MD, PhD, and his associates.
The investigators compared 461 patients who had onset of a clinically presumed synucleinopathy manifesting as parkinsonism from 1991 to 2010 with 452 age- and sex-matched referent participants from the general population who were free of parkinsonism and tremor of any type in the year of onset of the other patients’ synucleinopathies. Of the 461 patients with the presumed synucleinopathies, 316 (68.6%) died during follow-up and 311 had a known cause of death (98.4%). Of the 452 referent participants, 220 (48.7%) died during follow-up and 216 had a known cause of death (98.2%). The highest risk of death was among patients with MSA-p (hazard ratio, 10.51) when compared with referent participants. The remaining patients also had elevated risk of death: DLB (HR, 3.94), PDD (HR, 3.86), and PD (HR, 1.75).
Neurodegenerative disease was the most frequent cause of death among patients for all synucleinopathies (31.5%) and in PD alone (25.6%), and cardiovascular events were the second most common cause of death (15.7%). Among the referent participants, cardiovascular events were the most common cause of death (25.5%).
The results were consistent with the causes of death observed among patients with DLB, PDD, and MSA-p; however, the researchers said the sample size was too limited to observe a sufficient number of events. They also noted that there was no significant interaction with sex and age in predicting survival rates for any type of synucleinopathy.
“Our findings contribute important new evidence about the natural history and survival of people affected by synucleinopathies of various types,” the researchers concluded. “Our results may be helpful to guide clinicians counseling patients and caregivers.”
Find the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2017.0603).
FROM JAMA NEUROLOGY
Microneedle pretreatment shortened ALA incubation time
Pretreatment with microneedles provided a faster, less painful, way to treat facial actinic keratoses (AKs) with photodynamic therapy, with similar clearance rates as would be expected with traditional therapy, in a study of 33 patients.
This approach reduced the incubation time of aminolevulinic acid (ALA) to 20 minutes, with comparable results to one-hour ALA incubation times. “Interestingly, the secondary outcome of pain associated with blue light exposure during photodynamic therapy was nominal and not significantly different from the sham side,” reported Tatyana A. Petukhova, MD, and her associates in the department of dermatology at the University of California, Davis (JAMA Dermatol. 2017 May 17. doi: 10.1001/jamadermatol.2017.0849).
“Pain associated with PDT is the most severe adverse effect and may lead to interruption or discontinuation of treatment, resulting in refusal to repeat the process at a future date owing to unbearable discomfort,” they wrote. Patients also reported little to no swelling or pain after treatment and minimal erythema and peeling.
The randomized, split-face, single-blinded controlled trial enrolled 33 patients, with at least eight AKs on their faces, from a university dermatology outpatient clinic from 2015 to 2016. They were randomized to receive either 10 minutes or 20 minutes incubation time with ALA, and 32 completed the study. Those in the 20-minute group had a mean of 25 grade II facial AKs, and those in the 10-minute group had an average of 31 grade II facial AKs.
Before administration of ALA, each patient received pretreatment with a microneedle roller on one side of their face and a sham roller on the other side. On each half of their faces, the microneedle device (a single-use sterile array of microneedles measuring 200 mcm) or sham roller was rolled forward and backward eight times in four directions.
They were exposed to blue light for 1,000 seconds at an average wavelength of 478 nm, an overall fluence of 10 J/cm2, and advised to avoid sun exposure for 36 hours after treatment.
At follow-up one month later, among the patients with a 20-minute ALA incubation time, the mean AK clearance rate was 76% on the side with microneedle pretreatment, compared with 58% on the sham side (P less than .01). This included three patients with complete clearance. The efficacy of microneedle pretreatment with a 20-minute incubation time is similar to that of 1-hour incubation times with ALA. PDT typically uses 1-4 hours of incubation time.
Among the patients who received a 10-minute ALA incubation time, a mean of 43% of AKs on the microneedle side and 38% on the sham side cleared, a difference that was not statistically significant. Participants did not rate the pain as significantly different between each side of their face and both groups reported low levels of pain overall.
One limitation of the study was the short follow-up time. “Because actinic damage is cumulative, there is potential for thicker AKs to recur or for new lesions to develop during a longer follow-up period,” the authors noted.
The research was partly funded by an author’s University of California, Davis, Medical Student Research Fellowship. The authors reported having no disclosures.
The effectiveness of photodynamic therapy (PDT) as a field therapy option for actinic keratoses (AKs) has been well documented. However, treatment is limited by poor or variable transepidermal absorption owing to the hydrophilic nature of aminolevulinic acid (ALA).
To overcome the problem of transepidermal delivery, patients wait for hours at a time between ALA application and the light treatment. These prolonged incubation times limit usefulness. Petukhova et al. hypothesized that microneedles would enhance penetration and decrease incubation period without compromising safety and efficacy. The results suggest that an effective and safe PDT treatment can be achieved by using microneedles as means to expedite drug penetration. These results also suggest that further reduction of incubation time will not be achieved by better transepidermal penetration.
As envisioned in 1971, microneedles can have an important clinical role and can be an important tool in the dermatologist’s armamentarium. Microneedles are painless when compared with hypodermic needles, do not require specific training, minimize risk of needlestick injuries, can potentially reduce cost, and improve patient compliance and access. Therefore, microneedle-based devices can potentially be used at home by patients in a safe manner. Mostly in preclinical trials, as well as in some clinical trials, microneedles have been successfully used to deliver various drugs and vaccines.
Importantly, dermatologists are uniquely positioned to research this novel drug delivery method because they routinely treat cutaneous disease. This can be leveraged by dermatologists to use microneedles not only for dermal rejuvenation purposes but also to enhance drug delivery for dermatological indications. Therefore, the study by Petukhova et al. not only provides practical information for treatment of AKs with PDT but can also be viewed as a call for action to all dermatologists to lead innovation in the field and revolutionize dermatological drug delivery.
These comments are adapted from an accompanying editorial by Hadar Lev-Tov, MD, of the University of Florida, Miami. He reported having no disclosures.
The effectiveness of photodynamic therapy (PDT) as a field therapy option for actinic keratoses (AKs) has been well documented. However, treatment is limited by poor or variable transepidermal absorption owing to the hydrophilic nature of aminolevulinic acid (ALA).
To overcome the problem of transepidermal delivery, patients wait for hours at a time between ALA application and the light treatment. These prolonged incubation times limit usefulness. Petukhova et al. hypothesized that microneedles would enhance penetration and decrease incubation period without compromising safety and efficacy. The results suggest that an effective and safe PDT treatment can be achieved by using microneedles as means to expedite drug penetration. These results also suggest that further reduction of incubation time will not be achieved by better transepidermal penetration.
As envisioned in 1971, microneedles can have an important clinical role and can be an important tool in the dermatologist’s armamentarium. Microneedles are painless when compared with hypodermic needles, do not require specific training, minimize risk of needlestick injuries, can potentially reduce cost, and improve patient compliance and access. Therefore, microneedle-based devices can potentially be used at home by patients in a safe manner. Mostly in preclinical trials, as well as in some clinical trials, microneedles have been successfully used to deliver various drugs and vaccines.
Importantly, dermatologists are uniquely positioned to research this novel drug delivery method because they routinely treat cutaneous disease. This can be leveraged by dermatologists to use microneedles not only for dermal rejuvenation purposes but also to enhance drug delivery for dermatological indications. Therefore, the study by Petukhova et al. not only provides practical information for treatment of AKs with PDT but can also be viewed as a call for action to all dermatologists to lead innovation in the field and revolutionize dermatological drug delivery.
These comments are adapted from an accompanying editorial by Hadar Lev-Tov, MD, of the University of Florida, Miami. He reported having no disclosures.
The effectiveness of photodynamic therapy (PDT) as a field therapy option for actinic keratoses (AKs) has been well documented. However, treatment is limited by poor or variable transepidermal absorption owing to the hydrophilic nature of aminolevulinic acid (ALA).
To overcome the problem of transepidermal delivery, patients wait for hours at a time between ALA application and the light treatment. These prolonged incubation times limit usefulness. Petukhova et al. hypothesized that microneedles would enhance penetration and decrease incubation period without compromising safety and efficacy. The results suggest that an effective and safe PDT treatment can be achieved by using microneedles as means to expedite drug penetration. These results also suggest that further reduction of incubation time will not be achieved by better transepidermal penetration.
As envisioned in 1971, microneedles can have an important clinical role and can be an important tool in the dermatologist’s armamentarium. Microneedles are painless when compared with hypodermic needles, do not require specific training, minimize risk of needlestick injuries, can potentially reduce cost, and improve patient compliance and access. Therefore, microneedle-based devices can potentially be used at home by patients in a safe manner. Mostly in preclinical trials, as well as in some clinical trials, microneedles have been successfully used to deliver various drugs and vaccines.
Importantly, dermatologists are uniquely positioned to research this novel drug delivery method because they routinely treat cutaneous disease. This can be leveraged by dermatologists to use microneedles not only for dermal rejuvenation purposes but also to enhance drug delivery for dermatological indications. Therefore, the study by Petukhova et al. not only provides practical information for treatment of AKs with PDT but can also be viewed as a call for action to all dermatologists to lead innovation in the field and revolutionize dermatological drug delivery.
These comments are adapted from an accompanying editorial by Hadar Lev-Tov, MD, of the University of Florida, Miami. He reported having no disclosures.
Pretreatment with microneedles provided a faster, less painful, way to treat facial actinic keratoses (AKs) with photodynamic therapy, with similar clearance rates as would be expected with traditional therapy, in a study of 33 patients.
This approach reduced the incubation time of aminolevulinic acid (ALA) to 20 minutes, with comparable results to one-hour ALA incubation times. “Interestingly, the secondary outcome of pain associated with blue light exposure during photodynamic therapy was nominal and not significantly different from the sham side,” reported Tatyana A. Petukhova, MD, and her associates in the department of dermatology at the University of California, Davis (JAMA Dermatol. 2017 May 17. doi: 10.1001/jamadermatol.2017.0849).
“Pain associated with PDT is the most severe adverse effect and may lead to interruption or discontinuation of treatment, resulting in refusal to repeat the process at a future date owing to unbearable discomfort,” they wrote. Patients also reported little to no swelling or pain after treatment and minimal erythema and peeling.
The randomized, split-face, single-blinded controlled trial enrolled 33 patients, with at least eight AKs on their faces, from a university dermatology outpatient clinic from 2015 to 2016. They were randomized to receive either 10 minutes or 20 minutes incubation time with ALA, and 32 completed the study. Those in the 20-minute group had a mean of 25 grade II facial AKs, and those in the 10-minute group had an average of 31 grade II facial AKs.
Before administration of ALA, each patient received pretreatment with a microneedle roller on one side of their face and a sham roller on the other side. On each half of their faces, the microneedle device (a single-use sterile array of microneedles measuring 200 mcm) or sham roller was rolled forward and backward eight times in four directions.
They were exposed to blue light for 1,000 seconds at an average wavelength of 478 nm, an overall fluence of 10 J/cm2, and advised to avoid sun exposure for 36 hours after treatment.
At follow-up one month later, among the patients with a 20-minute ALA incubation time, the mean AK clearance rate was 76% on the side with microneedle pretreatment, compared with 58% on the sham side (P less than .01). This included three patients with complete clearance. The efficacy of microneedle pretreatment with a 20-minute incubation time is similar to that of 1-hour incubation times with ALA. PDT typically uses 1-4 hours of incubation time.
Among the patients who received a 10-minute ALA incubation time, a mean of 43% of AKs on the microneedle side and 38% on the sham side cleared, a difference that was not statistically significant. Participants did not rate the pain as significantly different between each side of their face and both groups reported low levels of pain overall.
One limitation of the study was the short follow-up time. “Because actinic damage is cumulative, there is potential for thicker AKs to recur or for new lesions to develop during a longer follow-up period,” the authors noted.
The research was partly funded by an author’s University of California, Davis, Medical Student Research Fellowship. The authors reported having no disclosures.
Pretreatment with microneedles provided a faster, less painful, way to treat facial actinic keratoses (AKs) with photodynamic therapy, with similar clearance rates as would be expected with traditional therapy, in a study of 33 patients.
This approach reduced the incubation time of aminolevulinic acid (ALA) to 20 minutes, with comparable results to one-hour ALA incubation times. “Interestingly, the secondary outcome of pain associated with blue light exposure during photodynamic therapy was nominal and not significantly different from the sham side,” reported Tatyana A. Petukhova, MD, and her associates in the department of dermatology at the University of California, Davis (JAMA Dermatol. 2017 May 17. doi: 10.1001/jamadermatol.2017.0849).
“Pain associated with PDT is the most severe adverse effect and may lead to interruption or discontinuation of treatment, resulting in refusal to repeat the process at a future date owing to unbearable discomfort,” they wrote. Patients also reported little to no swelling or pain after treatment and minimal erythema and peeling.
The randomized, split-face, single-blinded controlled trial enrolled 33 patients, with at least eight AKs on their faces, from a university dermatology outpatient clinic from 2015 to 2016. They were randomized to receive either 10 minutes or 20 minutes incubation time with ALA, and 32 completed the study. Those in the 20-minute group had a mean of 25 grade II facial AKs, and those in the 10-minute group had an average of 31 grade II facial AKs.
Before administration of ALA, each patient received pretreatment with a microneedle roller on one side of their face and a sham roller on the other side. On each half of their faces, the microneedle device (a single-use sterile array of microneedles measuring 200 mcm) or sham roller was rolled forward and backward eight times in four directions.
They were exposed to blue light for 1,000 seconds at an average wavelength of 478 nm, an overall fluence of 10 J/cm2, and advised to avoid sun exposure for 36 hours after treatment.
At follow-up one month later, among the patients with a 20-minute ALA incubation time, the mean AK clearance rate was 76% on the side with microneedle pretreatment, compared with 58% on the sham side (P less than .01). This included three patients with complete clearance. The efficacy of microneedle pretreatment with a 20-minute incubation time is similar to that of 1-hour incubation times with ALA. PDT typically uses 1-4 hours of incubation time.
Among the patients who received a 10-minute ALA incubation time, a mean of 43% of AKs on the microneedle side and 38% on the sham side cleared, a difference that was not statistically significant. Participants did not rate the pain as significantly different between each side of their face and both groups reported low levels of pain overall.
One limitation of the study was the short follow-up time. “Because actinic damage is cumulative, there is potential for thicker AKs to recur or for new lesions to develop during a longer follow-up period,” the authors noted.
The research was partly funded by an author’s University of California, Davis, Medical Student Research Fellowship. The authors reported having no disclosures.
Key clinical point:
Major finding: The mean facial AK clearance rate one month after microneedle pretreatment and 20 minutes incubation of ALA was 76%.
Data source: The findings are based on a randomized, controlled, single-blinded study of 33 outpatients with actinic keratoses.
Disclosures: The research was partly funded by an author’s University of California, Davis, Medical Student Research Fellowship. The authors reported having no disclosures.
Mindful kids, part 1: Origins and evidence
Open a magazine or turn on the radio and you are likely to hear someone extolling the benefits of mindfulness for any number of purposes, conditions, or age groups. Businesses, schools, and health care organizations are incorporating mindfulness techniques to boost employee, student, and patient well-being and engagement, as well as to help employers, teachers, and providers to thrive. In this two-part series, part 1 will attempt to distill some of the fundamentals with regard to the following questions: 1. What is mindfulness? 2. What is the evidence for mindfulness, particularly in youth? and 3. How would you apply mindfulness techniques in your office setting?
Mindfulness was largely brought into the mainstream health care world by Jon Kabat-Zinn, PhD, of the University of Massachusetts Medical Center, Worcester. Drawing on Buddhist traditions, he created a secularized version of meditative and movement techniques used for thousands of years to promote healthy living. A growing evidence base showed that these practices, combined in a formal curriculum dubbed mindfulness-based stress reduction (MBSR), could alleviate symptoms and distress in conditions as diverse as chronic pain, psoriasis, and anxiety. This has spawned numerous research programs and spin-offs, and remains a foundational approach to utilizing mindfulness in medical care. Dr. Kabat-Zinn’s definition of the term is thus worth noting – mindfulness is “the awareness that arises by paying attention on purpose, in the present moment, and nonjudgmentally.”1 Put simply, mindfulness means having your mind and your body in the same place at the same time. If your mind is wandering to what happened yesterday or planning for what might happen later today, then your mind and body are not in the same time. If your mind is thinking about what is going on at home while you are at work, or what your friends are doing, your mind and body are not in the same place.
A study of a modified version of Dr. Kabat-Zinn’s MBSR in middle schoolers in an inner city environment compared 12 weeks of mindfulness training versus a typical health curriculum discussing adolescence, stress, and puberty. In this inner city environment, students randomized to mindfulness training reported less depression, less hostility, fewer ruminations, and fewer PTSD symptoms as well as fewer physical complaints.10 Regarding clinical populations, mindfulness training in adolescents has shown promise for ADHD, with improvement in both core symptoms and functionality.11 This especially seems pronounced when caregivers are supported in learning mindful parenting techniques alongside their teens’ mindfulness training.12
In a general psychiatry clinic, an 8-week adolescent MBSR program was added to supplement treatment as usual – psychotherapy and medication management. Those randomized to mindfulness showed improvements in sleep and self-esteem, as well as a decline in depressive and anxiety symptoms, perceived stress, and interpersonal problems.13 Perhaps most impressively, half of the MBSR group dropped at least one diagnosis after the 8-week program, whereas none of those in the wait list group, receiving psychiatric specialty care as usual, decreased their diagnosis count.
While the sum of such research in adults and children builds a strong case for the value of mindfulness at both the universal (well-child check) and problem-focused levels, there are limitations to our knowledge base. The number of studies and total number of children and adolescents enrolled in mindfulness research is far fewer than in studies with adults. A variety of mindfulness practices have been incorporated into study interventions such that results are not always comparable and distinguishing the mechanism of action is difficult. Additionally, double-blind and placebo-controlled studies are harder to accomplish with such active interventions, although headway is being made.14
Despite what remains to be discovered, bringing mindfulness into the lives of children and adolescents seems increasingly sensible, given the growing body of scientific support for the benefits of mindfulness practices at the behavioral and functional neuroanatomic levels. As is the case with recommending healthy diets, exercise, and other universal health-promoting behaviors, the knowledge that mindfulness practices are beneficial may not be enough to get patients and their families engaged in these methods. The second article in this series will address some nuts and bolts of prescribing mindfulness in a pediatric health care setting.
Dr. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Robert Larner College of Medicine, Burlington. He said he has no relevant disclosures.
References
1. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness (New York: Bantam Books, Penguin Random House, 2013).
2. J Pers Soc Psychol. 2003 Apr;84(4):822-48.
3. Gen Hosp Psychiatry. 1982 Apr;4(1):33-47.
4. Am J Psychiatry. 1992 Jul;149(7):936-43.
5. Clin Psychol Rev. 2011 Aug;31(6):1041-56.
6. Neuroreport. 2005 Nov 28;16(17):1893-7.
7. Soc Cogn Affect Neurosci. 2010 Mar;5(1):11-7.
8. Neuroimage. 2009 Apr 15;45(3):672-8.
9. Psychiatry Res. 2011 Jan 30;191(1):36-43.
10. Pediatrics. 2016 Jan;137(1):e20152532.
11. J Atten Disord. 2008 May;11(6):737-46.
12. J Child Fam Stud. 2012 Oct;21(5):775-87.
13. J Consult Clin Psychol. 2009 Oct;77(5):855-66.
14. Biol Psychiatry. 2016 Jul 1;80(1):53-61.
Open a magazine or turn on the radio and you are likely to hear someone extolling the benefits of mindfulness for any number of purposes, conditions, or age groups. Businesses, schools, and health care organizations are incorporating mindfulness techniques to boost employee, student, and patient well-being and engagement, as well as to help employers, teachers, and providers to thrive. In this two-part series, part 1 will attempt to distill some of the fundamentals with regard to the following questions: 1. What is mindfulness? 2. What is the evidence for mindfulness, particularly in youth? and 3. How would you apply mindfulness techniques in your office setting?
Mindfulness was largely brought into the mainstream health care world by Jon Kabat-Zinn, PhD, of the University of Massachusetts Medical Center, Worcester. Drawing on Buddhist traditions, he created a secularized version of meditative and movement techniques used for thousands of years to promote healthy living. A growing evidence base showed that these practices, combined in a formal curriculum dubbed mindfulness-based stress reduction (MBSR), could alleviate symptoms and distress in conditions as diverse as chronic pain, psoriasis, and anxiety. This has spawned numerous research programs and spin-offs, and remains a foundational approach to utilizing mindfulness in medical care. Dr. Kabat-Zinn’s definition of the term is thus worth noting – mindfulness is “the awareness that arises by paying attention on purpose, in the present moment, and nonjudgmentally.”1 Put simply, mindfulness means having your mind and your body in the same place at the same time. If your mind is wandering to what happened yesterday or planning for what might happen later today, then your mind and body are not in the same time. If your mind is thinking about what is going on at home while you are at work, or what your friends are doing, your mind and body are not in the same place.
A study of a modified version of Dr. Kabat-Zinn’s MBSR in middle schoolers in an inner city environment compared 12 weeks of mindfulness training versus a typical health curriculum discussing adolescence, stress, and puberty. In this inner city environment, students randomized to mindfulness training reported less depression, less hostility, fewer ruminations, and fewer PTSD symptoms as well as fewer physical complaints.10 Regarding clinical populations, mindfulness training in adolescents has shown promise for ADHD, with improvement in both core symptoms and functionality.11 This especially seems pronounced when caregivers are supported in learning mindful parenting techniques alongside their teens’ mindfulness training.12
In a general psychiatry clinic, an 8-week adolescent MBSR program was added to supplement treatment as usual – psychotherapy and medication management. Those randomized to mindfulness showed improvements in sleep and self-esteem, as well as a decline in depressive and anxiety symptoms, perceived stress, and interpersonal problems.13 Perhaps most impressively, half of the MBSR group dropped at least one diagnosis after the 8-week program, whereas none of those in the wait list group, receiving psychiatric specialty care as usual, decreased their diagnosis count.
While the sum of such research in adults and children builds a strong case for the value of mindfulness at both the universal (well-child check) and problem-focused levels, there are limitations to our knowledge base. The number of studies and total number of children and adolescents enrolled in mindfulness research is far fewer than in studies with adults. A variety of mindfulness practices have been incorporated into study interventions such that results are not always comparable and distinguishing the mechanism of action is difficult. Additionally, double-blind and placebo-controlled studies are harder to accomplish with such active interventions, although headway is being made.14
Despite what remains to be discovered, bringing mindfulness into the lives of children and adolescents seems increasingly sensible, given the growing body of scientific support for the benefits of mindfulness practices at the behavioral and functional neuroanatomic levels. As is the case with recommending healthy diets, exercise, and other universal health-promoting behaviors, the knowledge that mindfulness practices are beneficial may not be enough to get patients and their families engaged in these methods. The second article in this series will address some nuts and bolts of prescribing mindfulness in a pediatric health care setting.
Dr. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Robert Larner College of Medicine, Burlington. He said he has no relevant disclosures.
References
1. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness (New York: Bantam Books, Penguin Random House, 2013).
2. J Pers Soc Psychol. 2003 Apr;84(4):822-48.
3. Gen Hosp Psychiatry. 1982 Apr;4(1):33-47.
4. Am J Psychiatry. 1992 Jul;149(7):936-43.
5. Clin Psychol Rev. 2011 Aug;31(6):1041-56.
6. Neuroreport. 2005 Nov 28;16(17):1893-7.
7. Soc Cogn Affect Neurosci. 2010 Mar;5(1):11-7.
8. Neuroimage. 2009 Apr 15;45(3):672-8.
9. Psychiatry Res. 2011 Jan 30;191(1):36-43.
10. Pediatrics. 2016 Jan;137(1):e20152532.
11. J Atten Disord. 2008 May;11(6):737-46.
12. J Child Fam Stud. 2012 Oct;21(5):775-87.
13. J Consult Clin Psychol. 2009 Oct;77(5):855-66.
14. Biol Psychiatry. 2016 Jul 1;80(1):53-61.
Open a magazine or turn on the radio and you are likely to hear someone extolling the benefits of mindfulness for any number of purposes, conditions, or age groups. Businesses, schools, and health care organizations are incorporating mindfulness techniques to boost employee, student, and patient well-being and engagement, as well as to help employers, teachers, and providers to thrive. In this two-part series, part 1 will attempt to distill some of the fundamentals with regard to the following questions: 1. What is mindfulness? 2. What is the evidence for mindfulness, particularly in youth? and 3. How would you apply mindfulness techniques in your office setting?
Mindfulness was largely brought into the mainstream health care world by Jon Kabat-Zinn, PhD, of the University of Massachusetts Medical Center, Worcester. Drawing on Buddhist traditions, he created a secularized version of meditative and movement techniques used for thousands of years to promote healthy living. A growing evidence base showed that these practices, combined in a formal curriculum dubbed mindfulness-based stress reduction (MBSR), could alleviate symptoms and distress in conditions as diverse as chronic pain, psoriasis, and anxiety. This has spawned numerous research programs and spin-offs, and remains a foundational approach to utilizing mindfulness in medical care. Dr. Kabat-Zinn’s definition of the term is thus worth noting – mindfulness is “the awareness that arises by paying attention on purpose, in the present moment, and nonjudgmentally.”1 Put simply, mindfulness means having your mind and your body in the same place at the same time. If your mind is wandering to what happened yesterday or planning for what might happen later today, then your mind and body are not in the same time. If your mind is thinking about what is going on at home while you are at work, or what your friends are doing, your mind and body are not in the same place.
A study of a modified version of Dr. Kabat-Zinn’s MBSR in middle schoolers in an inner city environment compared 12 weeks of mindfulness training versus a typical health curriculum discussing adolescence, stress, and puberty. In this inner city environment, students randomized to mindfulness training reported less depression, less hostility, fewer ruminations, and fewer PTSD symptoms as well as fewer physical complaints.10 Regarding clinical populations, mindfulness training in adolescents has shown promise for ADHD, with improvement in both core symptoms and functionality.11 This especially seems pronounced when caregivers are supported in learning mindful parenting techniques alongside their teens’ mindfulness training.12
In a general psychiatry clinic, an 8-week adolescent MBSR program was added to supplement treatment as usual – psychotherapy and medication management. Those randomized to mindfulness showed improvements in sleep and self-esteem, as well as a decline in depressive and anxiety symptoms, perceived stress, and interpersonal problems.13 Perhaps most impressively, half of the MBSR group dropped at least one diagnosis after the 8-week program, whereas none of those in the wait list group, receiving psychiatric specialty care as usual, decreased their diagnosis count.
While the sum of such research in adults and children builds a strong case for the value of mindfulness at both the universal (well-child check) and problem-focused levels, there are limitations to our knowledge base. The number of studies and total number of children and adolescents enrolled in mindfulness research is far fewer than in studies with adults. A variety of mindfulness practices have been incorporated into study interventions such that results are not always comparable and distinguishing the mechanism of action is difficult. Additionally, double-blind and placebo-controlled studies are harder to accomplish with such active interventions, although headway is being made.14
Despite what remains to be discovered, bringing mindfulness into the lives of children and adolescents seems increasingly sensible, given the growing body of scientific support for the benefits of mindfulness practices at the behavioral and functional neuroanatomic levels. As is the case with recommending healthy diets, exercise, and other universal health-promoting behaviors, the knowledge that mindfulness practices are beneficial may not be enough to get patients and their families engaged in these methods. The second article in this series will address some nuts and bolts of prescribing mindfulness in a pediatric health care setting.
Dr. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Robert Larner College of Medicine, Burlington. He said he has no relevant disclosures.
References
1. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness (New York: Bantam Books, Penguin Random House, 2013).
2. J Pers Soc Psychol. 2003 Apr;84(4):822-48.
3. Gen Hosp Psychiatry. 1982 Apr;4(1):33-47.
4. Am J Psychiatry. 1992 Jul;149(7):936-43.
5. Clin Psychol Rev. 2011 Aug;31(6):1041-56.
6. Neuroreport. 2005 Nov 28;16(17):1893-7.
7. Soc Cogn Affect Neurosci. 2010 Mar;5(1):11-7.
8. Neuroimage. 2009 Apr 15;45(3):672-8.
9. Psychiatry Res. 2011 Jan 30;191(1):36-43.
10. Pediatrics. 2016 Jan;137(1):e20152532.
11. J Atten Disord. 2008 May;11(6):737-46.
12. J Child Fam Stud. 2012 Oct;21(5):775-87.
13. J Consult Clin Psychol. 2009 Oct;77(5):855-66.
14. Biol Psychiatry. 2016 Jul 1;80(1):53-61.