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Low fish consumption linked to small increased MS risk
Key clinical point: Low fish consumption is associated with an increased risk of developing multiple sclerosis (MS); vitamin D does not mediate this association.
Major finding: Regardless of sun exposure habits, MS risk was higher with low fish consumption, including both lean and fatty fish (odds ratio, 1.2; 95% confidence interval, 1.1-1.4). The mediation analysis revealed that the effect mediated by vitamin D deficiency on this association was very small. A significant interaction was noted between DRB1*15:01 allele and both low sun exposure and low fish consumption.
Study details: The data come from 2 Swedish population-based case-control studies (6,914 patients with MS and 6,590 control participants).
Disclosures: The study was supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Dr Olsson reported receiving grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Brain Foundation. Dr Alfredsson reported receiving grants from the Swedish Research Council, the Swedish
Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation.
Citation: Hedström AK et al. Neurol Neuroimmunol Neuroinflamm. 2020 Apr 10. doi: 10.1212/NXI.0000000000000717.
Key clinical point: Low fish consumption is associated with an increased risk of developing multiple sclerosis (MS); vitamin D does not mediate this association.
Major finding: Regardless of sun exposure habits, MS risk was higher with low fish consumption, including both lean and fatty fish (odds ratio, 1.2; 95% confidence interval, 1.1-1.4). The mediation analysis revealed that the effect mediated by vitamin D deficiency on this association was very small. A significant interaction was noted between DRB1*15:01 allele and both low sun exposure and low fish consumption.
Study details: The data come from 2 Swedish population-based case-control studies (6,914 patients with MS and 6,590 control participants).
Disclosures: The study was supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Dr Olsson reported receiving grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Brain Foundation. Dr Alfredsson reported receiving grants from the Swedish Research Council, the Swedish
Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation.
Citation: Hedström AK et al. Neurol Neuroimmunol Neuroinflamm. 2020 Apr 10. doi: 10.1212/NXI.0000000000000717.
Key clinical point: Low fish consumption is associated with an increased risk of developing multiple sclerosis (MS); vitamin D does not mediate this association.
Major finding: Regardless of sun exposure habits, MS risk was higher with low fish consumption, including both lean and fatty fish (odds ratio, 1.2; 95% confidence interval, 1.1-1.4). The mediation analysis revealed that the effect mediated by vitamin D deficiency on this association was very small. A significant interaction was noted between DRB1*15:01 allele and both low sun exposure and low fish consumption.
Study details: The data come from 2 Swedish population-based case-control studies (6,914 patients with MS and 6,590 control participants).
Disclosures: The study was supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, and the Swedish Society for Medical Research. Dr Olsson reported receiving grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Brain Foundation. Dr Alfredsson reported receiving grants from the Swedish Research Council, the Swedish
Research Council for Health Working Life and Welfare, and the Swedish Brain Foundation.
Citation: Hedström AK et al. Neurol Neuroimmunol Neuroinflamm. 2020 Apr 10. doi: 10.1212/NXI.0000000000000717.
Dental amalgam fillings show no association with MS
Key clinical point: Mercury-containing dental amalgam fillings (AMF) are not associated with the risk of developing multiple sclerosis (MS).
Major finding: The risk of MS with AMF did not differ significantly between patients and control participants (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.648-1.046). MS was not associated with AMF irrespective of gender (women: aOR, 0.743; 95% CI, 0.552-1.000; men: aOR, 1.006; 95% CI, 0.670-1.509).
Study details: The data come from a Taiwanese population-based case-control study of 612 participants with MS and 612 matched participants without MS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Tseng CF et al. Int J Environ Res Public Health. 2020 Apr 12. doi: 10.3390/ijerph17082637.
Key clinical point: Mercury-containing dental amalgam fillings (AMF) are not associated with the risk of developing multiple sclerosis (MS).
Major finding: The risk of MS with AMF did not differ significantly between patients and control participants (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.648-1.046). MS was not associated with AMF irrespective of gender (women: aOR, 0.743; 95% CI, 0.552-1.000; men: aOR, 1.006; 95% CI, 0.670-1.509).
Study details: The data come from a Taiwanese population-based case-control study of 612 participants with MS and 612 matched participants without MS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Tseng CF et al. Int J Environ Res Public Health. 2020 Apr 12. doi: 10.3390/ijerph17082637.
Key clinical point: Mercury-containing dental amalgam fillings (AMF) are not associated with the risk of developing multiple sclerosis (MS).
Major finding: The risk of MS with AMF did not differ significantly between patients and control participants (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.648-1.046). MS was not associated with AMF irrespective of gender (women: aOR, 0.743; 95% CI, 0.552-1.000; men: aOR, 1.006; 95% CI, 0.670-1.509).
Study details: The data come from a Taiwanese population-based case-control study of 612 participants with MS and 612 matched participants without MS.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Citation: Tseng CF et al. Int J Environ Res Public Health. 2020 Apr 12. doi: 10.3390/ijerph17082637.
Medical societies advise on vitamin D in midst of COVID-19
Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.
The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.
They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.
The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”
It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”
The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.
Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
What role for vitamin D in COVID-19?
Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.
During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.
However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.
“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.
Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”
Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.
A version of this article originally appeared on Medscape.com.
Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.
The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.
They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.
The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”
It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”
The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.
Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
What role for vitamin D in COVID-19?
Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.
During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.
However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.
“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.
Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”
Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.
A version of this article originally appeared on Medscape.com.
Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.
The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.
They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.
The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”
It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”
The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.
Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.
What role for vitamin D in COVID-19?
Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.
During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.
However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.
“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.
Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”
Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.
A version of this article originally appeared on Medscape.com.
A Treatment Option for Patients with Metastatic Squamous NSCLC Who Progressed After Platinum-Based Chemotherapy
In this supplement to Federal Practitioner,
Dr. Raja Mudad, MD, discusses:
- The burden of squamous non-small cell lung cancer among active United States military and veterans
- Available treatment options for advanced metastatic squamous NSCLC
- Clinical trial data surrounding a treatment for patients with metastatic squamous NSCLC who have progressed after platinum-based chemotherapy, that can be used as early as second-line
(06/20) PC-US-115598
In this supplement to Federal Practitioner,
Dr. Raja Mudad, MD, discusses:
- The burden of squamous non-small cell lung cancer among active United States military and veterans
- Available treatment options for advanced metastatic squamous NSCLC
- Clinical trial data surrounding a treatment for patients with metastatic squamous NSCLC who have progressed after platinum-based chemotherapy, that can be used as early as second-line
(06/20) PC-US-115598
In this supplement to Federal Practitioner,
Dr. Raja Mudad, MD, discusses:
- The burden of squamous non-small cell lung cancer among active United States military and veterans
- Available treatment options for advanced metastatic squamous NSCLC
- Clinical trial data surrounding a treatment for patients with metastatic squamous NSCLC who have progressed after platinum-based chemotherapy, that can be used as early as second-line
(06/20) PC-US-115598
AI markers can predict progression, survival in prostate cancer
An AI-based Gleason score – derived from 7,267 digitized biopsy slides, pathology reports, and clinical data from patient electronic medical records – was calculated for each of 599 prostate cancer patients.
The AI scores were compared with pathologists’ Gleason scores, which were obtained from pathology reports for each of the patients.
The two scores were “highly correlated,” according to investigators. The area under the curve (AUC) for the 7-year mortality rate was 0.667 for the AI-based scores and 0.659 for the pathologists’ scores.
The investigators also found that markers extracted using AI-based algorithms could predict disease progression in patients with low- and higher-grade disease.
Daphna Laifenfeld, PhD, chief scientific officer of Ibex Medical Analytics in Tel Aviv, reported these results in a poster at the AACR virtual meeting II. Ibex Medical Analytics is the company that developed the AI-based algorithms and Gleason score (the Ibex score).
In addition to comparing the Ibex Gleason scores with pathologists’ scores, Dr. Laifenfeld and colleagues sought to “develop AI markers – computational features extracted from slides using AI-based algorithms – that can predict disease progression in low-, and separately, higher-grade patients.”
Information extracted using the algorithms included Gleason scores; perineural invasion; and other characteristics such as inflammation, high-grade prostatic intraepithelial neoplasia, and atrophy.
“We used data ... to address each aim, analyzing hundreds of patients in each comparison, and employed logistic regression to develop the predictive models,” Dr. Laifenfeld said.
Of the 357 patients evaluated, 180 had low-grade disease, defined by a prebiopsy prostate-specific antigen (PSA) level less than 10 ng/mL (Gleason group 1), and 177 patients had higher-grade disease (Gleason group 2 or higher).
Gleason group 1 patients were considered to have progressed if they developed higher-grade cancer, underwent prostatectomy, or if their cancer had metastasized. Gleason group 2 and above patients were considered to have progressed if their cancer metastasized or if they had a postprostatectomy PSA level greater than 4 ng/ml.
In Gleason group 1 patients, combining multiple features from the pathology report with prebiopsy PSA levels was shown to predict disease progression better than prebiopsy PSA levels alone (AUC, 0.687).
“Importantly, AI markers that combine features automatically extracted by Ibex with prebiopsy PSA levels are even better associated with progression (AUC, 0.748),” Dr. Laifenfeld said.
Similarly, in the Gleason group 2 and above patients, the AI markers that combine Ibex-extracted features with prebiopsy PSA levels were also highly associated with progression (AUC, 0.862 vs. AUC, 0.77 for the non–Ibex-based approach) and can be used for patient stratification, Dr. Laifenfeld said.
“For each patient, we can predict whether or not their disease will progress,” she said. “[T]his type of stratification can then be used to support clinical disease management decisions, and [it can be used] in the course of drug development for patient stratification and trial enrichment strategies.”
Dr. Laifenfeld and some coinvestigators are employed by Ibex Medical Analytics.
SOURCE: Laifenfeld D et al. AACR 2020, Abstract 867.
An AI-based Gleason score – derived from 7,267 digitized biopsy slides, pathology reports, and clinical data from patient electronic medical records – was calculated for each of 599 prostate cancer patients.
The AI scores were compared with pathologists’ Gleason scores, which were obtained from pathology reports for each of the patients.
The two scores were “highly correlated,” according to investigators. The area under the curve (AUC) for the 7-year mortality rate was 0.667 for the AI-based scores and 0.659 for the pathologists’ scores.
The investigators also found that markers extracted using AI-based algorithms could predict disease progression in patients with low- and higher-grade disease.
Daphna Laifenfeld, PhD, chief scientific officer of Ibex Medical Analytics in Tel Aviv, reported these results in a poster at the AACR virtual meeting II. Ibex Medical Analytics is the company that developed the AI-based algorithms and Gleason score (the Ibex score).
In addition to comparing the Ibex Gleason scores with pathologists’ scores, Dr. Laifenfeld and colleagues sought to “develop AI markers – computational features extracted from slides using AI-based algorithms – that can predict disease progression in low-, and separately, higher-grade patients.”
Information extracted using the algorithms included Gleason scores; perineural invasion; and other characteristics such as inflammation, high-grade prostatic intraepithelial neoplasia, and atrophy.
“We used data ... to address each aim, analyzing hundreds of patients in each comparison, and employed logistic regression to develop the predictive models,” Dr. Laifenfeld said.
Of the 357 patients evaluated, 180 had low-grade disease, defined by a prebiopsy prostate-specific antigen (PSA) level less than 10 ng/mL (Gleason group 1), and 177 patients had higher-grade disease (Gleason group 2 or higher).
Gleason group 1 patients were considered to have progressed if they developed higher-grade cancer, underwent prostatectomy, or if their cancer had metastasized. Gleason group 2 and above patients were considered to have progressed if their cancer metastasized or if they had a postprostatectomy PSA level greater than 4 ng/ml.
In Gleason group 1 patients, combining multiple features from the pathology report with prebiopsy PSA levels was shown to predict disease progression better than prebiopsy PSA levels alone (AUC, 0.687).
“Importantly, AI markers that combine features automatically extracted by Ibex with prebiopsy PSA levels are even better associated with progression (AUC, 0.748),” Dr. Laifenfeld said.
Similarly, in the Gleason group 2 and above patients, the AI markers that combine Ibex-extracted features with prebiopsy PSA levels were also highly associated with progression (AUC, 0.862 vs. AUC, 0.77 for the non–Ibex-based approach) and can be used for patient stratification, Dr. Laifenfeld said.
“For each patient, we can predict whether or not their disease will progress,” she said. “[T]his type of stratification can then be used to support clinical disease management decisions, and [it can be used] in the course of drug development for patient stratification and trial enrichment strategies.”
Dr. Laifenfeld and some coinvestigators are employed by Ibex Medical Analytics.
SOURCE: Laifenfeld D et al. AACR 2020, Abstract 867.
An AI-based Gleason score – derived from 7,267 digitized biopsy slides, pathology reports, and clinical data from patient electronic medical records – was calculated for each of 599 prostate cancer patients.
The AI scores were compared with pathologists’ Gleason scores, which were obtained from pathology reports for each of the patients.
The two scores were “highly correlated,” according to investigators. The area under the curve (AUC) for the 7-year mortality rate was 0.667 for the AI-based scores and 0.659 for the pathologists’ scores.
The investigators also found that markers extracted using AI-based algorithms could predict disease progression in patients with low- and higher-grade disease.
Daphna Laifenfeld, PhD, chief scientific officer of Ibex Medical Analytics in Tel Aviv, reported these results in a poster at the AACR virtual meeting II. Ibex Medical Analytics is the company that developed the AI-based algorithms and Gleason score (the Ibex score).
In addition to comparing the Ibex Gleason scores with pathologists’ scores, Dr. Laifenfeld and colleagues sought to “develop AI markers – computational features extracted from slides using AI-based algorithms – that can predict disease progression in low-, and separately, higher-grade patients.”
Information extracted using the algorithms included Gleason scores; perineural invasion; and other characteristics such as inflammation, high-grade prostatic intraepithelial neoplasia, and atrophy.
“We used data ... to address each aim, analyzing hundreds of patients in each comparison, and employed logistic regression to develop the predictive models,” Dr. Laifenfeld said.
Of the 357 patients evaluated, 180 had low-grade disease, defined by a prebiopsy prostate-specific antigen (PSA) level less than 10 ng/mL (Gleason group 1), and 177 patients had higher-grade disease (Gleason group 2 or higher).
Gleason group 1 patients were considered to have progressed if they developed higher-grade cancer, underwent prostatectomy, or if their cancer had metastasized. Gleason group 2 and above patients were considered to have progressed if their cancer metastasized or if they had a postprostatectomy PSA level greater than 4 ng/ml.
In Gleason group 1 patients, combining multiple features from the pathology report with prebiopsy PSA levels was shown to predict disease progression better than prebiopsy PSA levels alone (AUC, 0.687).
“Importantly, AI markers that combine features automatically extracted by Ibex with prebiopsy PSA levels are even better associated with progression (AUC, 0.748),” Dr. Laifenfeld said.
Similarly, in the Gleason group 2 and above patients, the AI markers that combine Ibex-extracted features with prebiopsy PSA levels were also highly associated with progression (AUC, 0.862 vs. AUC, 0.77 for the non–Ibex-based approach) and can be used for patient stratification, Dr. Laifenfeld said.
“For each patient, we can predict whether or not their disease will progress,” she said. “[T]his type of stratification can then be used to support clinical disease management decisions, and [it can be used] in the course of drug development for patient stratification and trial enrichment strategies.”
Dr. Laifenfeld and some coinvestigators are employed by Ibex Medical Analytics.
SOURCE: Laifenfeld D et al. AACR 2020, Abstract 867.
FROM AACR 2020
Hyperglycemia predicts COVID-19 death even without diabetes
new research indicates.
The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.
Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.
Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.
Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.
“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.
“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
Hyperglycemia predicts COVID-19 death, complications
The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.
Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.
“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.
Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications.
The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.
Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.
In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).
Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).
Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.
Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.
Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.
The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.
This article first appeared on Medscape.com.
new research indicates.
The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.
Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.
Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.
Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.
“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.
“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
Hyperglycemia predicts COVID-19 death, complications
The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.
Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.
“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.
Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications.
The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.
Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.
In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).
Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).
Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.
Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.
Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.
The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.
This article first appeared on Medscape.com.
new research indicates.
The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.
Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.
Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.
Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.
“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.
“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
Hyperglycemia predicts COVID-19 death, complications
The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.
Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.
“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.
Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications.
The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.
Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.
In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).
Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).
Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.
Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.
Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.
The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.
This article first appeared on Medscape.com.
Does obesity reduce drug efficacy in breast cancer?
Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.
A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.
That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.
“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.
If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.
The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.
“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
Worse outcomes in patients with high BMI
The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.
It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.
Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.
The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”
The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.
Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”
Experts approached by Medscape Medical News for comment agreed.
“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.
These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.
Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”
Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.
“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.
“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.
Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”
Study details
For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.
The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.
The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.
The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).
“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.
It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.
The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg2.
Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.
The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.
This story first appeared on Medscape.com.
Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.
A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.
That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.
“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.
If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.
The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.
“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
Worse outcomes in patients with high BMI
The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.
It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.
Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.
The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”
The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.
Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”
Experts approached by Medscape Medical News for comment agreed.
“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.
These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.
Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”
Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.
“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.
“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.
Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”
Study details
For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.
The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.
The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.
The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).
“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.
It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.
The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg2.
Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.
The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.
This story first appeared on Medscape.com.
Obesity has been shown to have an impact on the risk of developing breast cancer and on prognosis. A new study suggests that it may also have an effect on treatment.
A high body mass index (BMI) at the time of breast cancer diagnosis could reduce the efficacy of taxane-based adjuvant chemotherapy, worsening survival outcomes, the study suggests.
That study investigated docetaxel (Taxotere), which is a “lipophilic drug, suggesting that fat present in the body could absorb part of the drug before it can reach the tumor,” commented lead author Christine Desmedt, PhD, of the Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.
“These results also make us wonder whether other chemotherapy drugs from the same family, like paclitaxel (Taxol), will show the same effect,” she said in a statement.
If follow-up research confirms that the findings are related solely to the pharmacologic characteristics of docetaxel, the results may also apply to its use in other types of cancer, including prostate cancer and lung cancer, she added.
The finding that taxane chemotherapy was less effective in overweight patients “is a provocative observation,” commented Harold Burstein, MD, PhD, an oncologist and clinical investigator at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts.
“It should be explored in other trials that looked at adding taxanes to standard chemotherapy,” he told Medscape Medical News.
Worse outcomes in patients with high BMI
The study, published online in the Journal of Clinical Oncology, was a retrospective reanalysis of data from the phase 3 BIG 2-98 trial.
It shows that overweight and obese patients treated with a chemotherapy regimen based on docetaxel had significantly worse disease-free survival (DFS) and overall survival (OS) compared with lean patients treated with the same chemotherapy regimen.
Conversely, for patients treated with an adjuvant chemotherapy regimen that did not include docetaxel, there was no difference in DFS, OS, or in the rates of distant metastases in regard to BMI.
The finding “highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer,” say the researchers. “These results now must be confirmed in additional series.”
The findings call into question results from earlier randomized clinical trials that did not evaluate the efficacy of most cancer drugs on the basis of patient adiposity, the researchers say.
Desmedt emphasized that more research is needed “before changes in treatment can be implemented.”
Experts approached by Medscape Medical News for comment agreed.
“It is important to remember that breast cancer patients needing chemotherapy should still receive the usual chemotherapy regimens, including taxanes, regardless of their weight or habitus,” commented Burstein, who is also professor of medicine at Harvard University.
These data highlight a persistent disparity in breast cancer outcomes, he told Medscape Medical News. Previous studies have shown that overweight patients often have less favorable outcomes. “There are many contributors to poor health outcomes in people with higher BMI, including concurrent health issues such as diabetes and/or hypertension, and unfortunately, the clear link between socioeconomic status and obesity,” he added.
Megan Kruse, MD, of the department of hematology and medical oncology at the Cleveland Clinic, said she “would not make changes in my treatment recommendations based on this study alone.”
Kruse was surprised that when the analysis was restricted to patients who received a relative dose intensity ≥85% for docetaxel, the same reduced rates of DFS and OS were seen as in patients with a high BMI.
“One may have suspected, based on the overall results, that patients with inferior survival outcomes actually received less chemotherapy due to [the] tendency to cap doses of chemotherapy in patients with high BMIs,” she explained.
“Since this analysis keeps dose intensity in mind, the association between BMI and survival outcomes is stronger in my mind. It does not, however, rule out that there are other confounding factors,” Kruse told Medscape Medical News.
Whether the results can be replicated in other retrospective clinical trials remains to be seen, she commented. Noting that the investigators plan to develop a prospective pharmacokinetics study across the BMI spectrum, Kruse added: “This will be of great interest as we plan curative-intent chemotherapy trials moving forward.”
Study details
For the current study, the investigators analyzed data from all 2,887 breast cancer patients enrolled in the adjuvant BIG 2-98 trial. They compared the survival outcomes of those who received docetaxel-based chemotherapy with those who received non-docetaxel-based chemotherapy in relation to their BMI. Patients with a BMI of 18.5 to 25 kg/m were classified as lean; patients with a BMI of 25-30 were classified as overweight; and those with a BMI ≥30 were classified as obese.
The researchers also assessed a second-order interaction on the basis of treatment, BMI, and estrogen receptor (ER) status.
The results showed that in the overweight women, compared with lean women, the adjusted hazard ratios (HRs) for DFS and OS were 1.12 (95% CI, 98 – 1.50; P = .21) and 1.27 (95% CI,101 – 1.60; P = .04), respectively. For obese vs lean patients, the HRs for DFS and OS were 1.32 (95% CI, 108 – 162; P = .007) and 1.63 (95% CI, 1.27 – 2.09; P < .001), respectively.
The survival outcomes were similar when only those patients who received a relative dose intensity ≥85% for docetaxel were considered. However, when ER-negative and ER-positive tumors were considered separately, the researchers found evidence of a joint modifying role of BMI and ER status on treatment effect for DFS (adjusted P =.06) and OS (adjusted P = .04).
“[I]t appears that the benefit for docetaxel-based versus nondocetaxel-based treatment could be limited to lean and overweight patients with ER-positive tumors and, possibly, to lean patients with ER-negative tumors…,” Desmedt and colleagues comment.
It may even be possible that docetaxel-based treatment could be detrimental for overweight patients with ER-negative tumors, they note, but warn that these results should be interpreted with caution.
The investigators note that, worldwide, the proportion of women with increased adiposity has been increasing for decades. In Europe, it is estimated that more than 50% of women are overweight and obese. In the United States, almost 64% of women have a BMI >25 kg/mg2.
Previous studies have shown that, in postmenopausal women, a high BMI is associated with a higher risk of developing breast cancer and that, in women who do develop breast cancer, the prognosis is worse. In addition, a recent study demonstrated that increased adiposity can raise the risk for breast cancer in postmenopausal women whose BMI is in the normal range.
The study was funded in part by Fondation Cancer Luxemburg and Associazione Italiana per la Ricerca sul Cancro AIRC. Desmedt has disclosed no relevant financial relationships. A number of study coauthors reported relationships with industry.
This story first appeared on Medscape.com.
FDA expands Dysport use for cerebral palsy–related spasticity
– for patients as young as 2 years and older, according to manufacturer Ipsen Biopharmaceuticals.
When Dysport (abobotulinumtoxinA) initially was approved for treating pediatric lower limb spasticity by the FDA in 2016, Ipsen was granted Orphan Drug exclusivity for children whose lower-limb spasticity was caused by cerebral palsy. In 2019, Dysport was approved by the FDA for treating of upper-limb spasticity in children 2 years older. But if that spasticity was caused by cerebral palsy, Dysport could be used to treat it only through Orphan Drug exclusivity granted to another manufacturer, according to an Ipsen press release.
“The proactive step to resolve the uncertainty created by the previous CP [cerebral palsy] carve out enables us as physicians to prescribe consistent therapy for pediatric patients experiencing both upper- and lower-limb spasticity,” Sarah Helen Evans, MD, division chief of rehabilitation medicine in the department of pediatrics at the Children’s Hospital of Philadelphia, said in the press release.
The most common adverse effects among children with lower-limb spasticity treated with Dysport were nasopharyngitis, cough, and pyrexia. Among children with upper-limb spasticity, the most common effects associated with Dysport treatment were upper respiratory tract infection and pharyngitis.
The press release also included a warning of the distant spread of the botulinum toxin from the area of injection hours to weeks afterward, causing symptoms including blurred vision, generalized muscle weakness, and swallowing and breathing difficulties that can be life threatening; there have been reports of death.
Suspected adverse effects can be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
– for patients as young as 2 years and older, according to manufacturer Ipsen Biopharmaceuticals.
When Dysport (abobotulinumtoxinA) initially was approved for treating pediatric lower limb spasticity by the FDA in 2016, Ipsen was granted Orphan Drug exclusivity for children whose lower-limb spasticity was caused by cerebral palsy. In 2019, Dysport was approved by the FDA for treating of upper-limb spasticity in children 2 years older. But if that spasticity was caused by cerebral palsy, Dysport could be used to treat it only through Orphan Drug exclusivity granted to another manufacturer, according to an Ipsen press release.
“The proactive step to resolve the uncertainty created by the previous CP [cerebral palsy] carve out enables us as physicians to prescribe consistent therapy for pediatric patients experiencing both upper- and lower-limb spasticity,” Sarah Helen Evans, MD, division chief of rehabilitation medicine in the department of pediatrics at the Children’s Hospital of Philadelphia, said in the press release.
The most common adverse effects among children with lower-limb spasticity treated with Dysport were nasopharyngitis, cough, and pyrexia. Among children with upper-limb spasticity, the most common effects associated with Dysport treatment were upper respiratory tract infection and pharyngitis.
The press release also included a warning of the distant spread of the botulinum toxin from the area of injection hours to weeks afterward, causing symptoms including blurred vision, generalized muscle weakness, and swallowing and breathing difficulties that can be life threatening; there have been reports of death.
Suspected adverse effects can be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
– for patients as young as 2 years and older, according to manufacturer Ipsen Biopharmaceuticals.
When Dysport (abobotulinumtoxinA) initially was approved for treating pediatric lower limb spasticity by the FDA in 2016, Ipsen was granted Orphan Drug exclusivity for children whose lower-limb spasticity was caused by cerebral palsy. In 2019, Dysport was approved by the FDA for treating of upper-limb spasticity in children 2 years older. But if that spasticity was caused by cerebral palsy, Dysport could be used to treat it only through Orphan Drug exclusivity granted to another manufacturer, according to an Ipsen press release.
“The proactive step to resolve the uncertainty created by the previous CP [cerebral palsy] carve out enables us as physicians to prescribe consistent therapy for pediatric patients experiencing both upper- and lower-limb spasticity,” Sarah Helen Evans, MD, division chief of rehabilitation medicine in the department of pediatrics at the Children’s Hospital of Philadelphia, said in the press release.
The most common adverse effects among children with lower-limb spasticity treated with Dysport were nasopharyngitis, cough, and pyrexia. Among children with upper-limb spasticity, the most common effects associated with Dysport treatment were upper respiratory tract infection and pharyngitis.
The press release also included a warning of the distant spread of the botulinum toxin from the area of injection hours to weeks afterward, causing symptoms including blurred vision, generalized muscle weakness, and swallowing and breathing difficulties that can be life threatening; there have been reports of death.
Suspected adverse effects can be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Subcutaneous nemolizumab eases itching for atopic dermatitis
of 215 patients in Japan.
Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.
In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.
In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.
At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).
In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.
During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.
Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.
The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.
However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.
“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.
Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”
Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.
One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.
The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.
SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.
of 215 patients in Japan.
Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.
In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.
In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.
At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).
In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.
During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.
Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.
The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.
However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.
“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.
Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”
Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.
One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.
The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.
SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.
of 215 patients in Japan.
Controlling the pruritus associated with atopic dermatitis (AD) can have a significant impact on patients’ quality of life, wrote Kenji Kabashima, MD, PhD, of the department of dermatology at Kyoto University, and coauthors. Frequent scratching can cause not only mechanical skin damage, but also may enhance inflammatory reactions and contribute to sleep problems.
In earlier phase studies, nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A, showed efficacy in reducing pruritus in patients with AD, but has not been well studied in patients who are also using topical agents, they wrote.
In the study published in the New England Journal of Medicine, the researchers randomized 143 patients with AD and moderate to severe pruritus to 60 mg of subcutaneous nemolizumab and 72 patients to a placebo every 4 weeks for 16 weeks. All patients were aged 13 years and older with a confirmed AD diagnosis and a history of inadequate response to or inability to use treatments, including topical glucocorticoids and oral antihistamines. Their average age was 40 years, approximately two-thirds were male, and the average disease duration was approximately 30 years. Topical treatments included a medium potency glucocorticoid in 97% of patients in both groups, and a topical calcineurin inhibitor in 41% of those on nemolizumab, and 40% of those on placebo; almost 90% of the patients in both groups were on oral antihistamines.
At 16 weeks, scores on the visual analog scale for pruritus (the primary outcome) significantly improved from baseline in the nemolizumab group, compared with the placebo group (a mean change of –42.8% and –21.4%, respectively, P < .001).
In addition, more patients in the nemolizumab group, compared with the placebo group (40% vs. 22%) achieved a score of 4 or less on the Dermatology Life Quality Index, with lower scores reflecting less impact of disease on daily life. In addition, more patients in the nemolizumab group, compared with the placebo group (55% vs. 21%) achieved a score of 7 or less on the Insomnia Severity Index.
During the study, 71% of the patients in each group reported adverse events, most were mild or moderate. The most common adverse event was worsening AD, reported by 24% of the nemolizumab patients and 21% of the placebo patients. Reactions related to the injection occurred in 8% of nemolizumab patients and 3% of placebo patients. Cytokine abnormalities, which included an increased level of thymus and activation regulated chemokine, were reported in 10 (7%) of the patients on nemolizumab, none of which occurred in those on placebo. “Most were not accompanied by a worsening of signs of or the extent of atopic dermatitis,” the authors wrote.
Severe adverse events were reported in three patients (2%) in the nemolizumab group, which were Meniere’s disease, acute pancreatitis, and AD in one patient each. No severe adverse events were reported in the placebo group. In addition, three patients in the nemolizumab group experienced four treatment-related adverse events that led them to discontinue treatment: AD, Meniere’s disease, alopecia, and peripheral edema.
The study findings were limited by several factors including the relatively short treatment period, inclusion only of Japanese patients, inclusion of patients aged as young as 13 years, and the inability to draw conclusions from the secondary endpoints such as quality of life and sleep issues, the researchers noted.
However, the results suggest that “nemolizumab plus topical agents may ameliorate both pruritus and signs of eczema and may lessen the severity of atopic dermatitis by disrupting the itch-scratch cycle,” they added.
“Novel therapies [for AD] are needed, as there are still patients who need better disease control despite current therapies, and AD is a heterogeneous disease that may need different treatment approaches,” Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, said in an interview.
Dr. Simpson, who was not an investigator in this study, said that he was somewhat surprised that the itch reduction was lower in the current study, compared with previous studies by the same group. Also surprising was the increase in cytokine abnormalities in the nemolizumab group, which “needs further study.”
Overall, the data “provide support that blockade of the IL-31 receptor improves itch in AD and appears to have some effect on inflammation,” Dr. Simpson said.
One challenge to the clinical use of nemolizumab will be identifying “where this type of drug fits into the treatment paradigm,” and determining whether specific patients whose disease is driven more by this neuroimmune pathway could benefit more than with the traditional IL-4 or IL-13 blockade, he said.
The study was supported by Maruho. Dr. Kabashima disclosed consulting fees from Maruho and two coauthors were Maruho employees. Dr. Simpson had no financial conflicts relevant to this study, but he reported receiving research grants and other financial relationships with manufacturers of AD therapies.
SOURCE: Kabashima K et al. N Engl J Med. 2020 Jul 9. doi: 10.1056/NEJMoa1917006.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Infants around the world with bronchiolitis received excess tests despite guidelines
While guidelines for bronchiolitis aim to reduce gratuitous tests and treatments, one-third of infants presenting at EDs with bronchiolitis receive an unnecessary intervention, according to a new global study.
For infants with symptoms of bronchiolitis, viral testing, blood tests, and chest x-rays are discouraged in most cases. Antibiotics are not recommended as treatment.
In a study published in Pediatrics, Amy Zipursky, MD, of the Hospital for Sick Children and the University of Toronto, and colleagues, reviewed records for 2,359 infants aged 2-11 months diagnosed with bronchiolitis during the year 2013. The data came from a network of 38 EDs in the Australia, Canada, Ireland, New Zealand, Portugal, Spain, the United Kingdom, and the United States.
Dr. Zipursky and colleagues found that, while 8% of infants in the cohort had been treated with antibiotics, 33% had received at least one nonrecommended test, with rates ranging widely across regions. In the United Kingdom and Ireland, for example, only 15% received such a test, compared with 50% in Spain and Portugal.
Of the children given antibiotics, two-thirds had suspected bacterial infections, the researchers found. Antibiotic use was highest in the United States, at 11% of infants seen for bronchiolitis, and lowest in the United Kingdom and Ireland at 4%. Administration of chest x-rays – which occurred in nearly a quarter of the cohort – increased the likelihood of antibiotics being administered (odds ratio, 2.29; 95% confidence interval, 1.62-3.24) independent of fever or severe symptoms.
The most common nonrecommended tests performed in the study were:
- Nasopharyngeal viral testing without admission to hospital (n = 591).
- Chest x-ray without ICU admission (n = 507).
- Complete blood counts (n = 222).
- Blood cultures (n = 129).
- Urinalysis in the absence of fever (n = 86).
- Febrile infants 3 months of age or less had blood cultures (n = 49).
In some treatment centers the rate of nonrecommended tests performed was 6%, while others saw rates of 74%.
“Despite the evidence that laboratory testing rarely impacts bronchiolitis management and that bacterial infections in bronchiolitis are uncommon, our study reveals that these tests continue to be performed frequently in many parts of the world,” Dr. Zipursky and colleagues wrote in their analysis.
“Plausible reasons may include ‘automatic’ blood draws with intravenous placement, uncertainty about institutional policies, perceived need for reassurance about the diagnosis, perception of ‘doing something,’ and parental desire for a viral label,” the authors surmised. “Because parental pressure to provide interventions may be a driver of care in infants with bronchiolitis in some countries, ED clinicians need to have higher confidence in the evidence-based bronchiolitis care and convey this trust to families.”
The researchers listed among the weaknesses of their study its retrospective design, and that results from x-rays and lab tests performed were not available.
In an editorial comment accompanying the study, Joseph J. Zorc, MD, of Children’s Hospital of Philadelphia and the University of Pennsylvania in Philadelphia, noted that some of the regional differences seen in the study may be attributable to different clinical criteria used to diagnose bronchiolitis. In the United Kingdom, for example, national guidelines include the presence of crackles, while in North America guidelines focus on wheeze. “Perhaps clinicians in the United Kingdom accept the presence of crackles as an expected finding in infant with bronchiolitis and are less likely to order imaging,” Dr. Zorc said (Pediatrics. 2020 Jul 13;146[2]:e20193684).
He also pointed out that the coronavirus pandemic caused by SARS-CoV-2 (COVID- 19) could have an impact on global testing and treatment practices for bronchiolitis, as coronaviruses are a known cause of bronchiolitis. The Pediatric Emergency Research Network, comprising the 38 EDs from which Dr. Zipursky and colleagues drew their data, is conducting a prospective study looking at pediatric disease caused by SARS-CoV-2.
The “collaboration of international networks of pediatric emergency providers is an encouraging sign of potential opportunities to come ... [providing] an opportunity to evaluate variation that can lead to innovation,” Dr. Zorc concluded.
Dr. Zipursky and colleagues reported no external funding or relevant financial disclosures. Dr. Zorc reported no relevant conflicts of interest.
SOURCE: Zipursky A et al. Pediatrics. 2020 Jul 13;146(2):e2020002311.
While guidelines for bronchiolitis aim to reduce gratuitous tests and treatments, one-third of infants presenting at EDs with bronchiolitis receive an unnecessary intervention, according to a new global study.
For infants with symptoms of bronchiolitis, viral testing, blood tests, and chest x-rays are discouraged in most cases. Antibiotics are not recommended as treatment.
In a study published in Pediatrics, Amy Zipursky, MD, of the Hospital for Sick Children and the University of Toronto, and colleagues, reviewed records for 2,359 infants aged 2-11 months diagnosed with bronchiolitis during the year 2013. The data came from a network of 38 EDs in the Australia, Canada, Ireland, New Zealand, Portugal, Spain, the United Kingdom, and the United States.
Dr. Zipursky and colleagues found that, while 8% of infants in the cohort had been treated with antibiotics, 33% had received at least one nonrecommended test, with rates ranging widely across regions. In the United Kingdom and Ireland, for example, only 15% received such a test, compared with 50% in Spain and Portugal.
Of the children given antibiotics, two-thirds had suspected bacterial infections, the researchers found. Antibiotic use was highest in the United States, at 11% of infants seen for bronchiolitis, and lowest in the United Kingdom and Ireland at 4%. Administration of chest x-rays – which occurred in nearly a quarter of the cohort – increased the likelihood of antibiotics being administered (odds ratio, 2.29; 95% confidence interval, 1.62-3.24) independent of fever or severe symptoms.
The most common nonrecommended tests performed in the study were:
- Nasopharyngeal viral testing without admission to hospital (n = 591).
- Chest x-ray without ICU admission (n = 507).
- Complete blood counts (n = 222).
- Blood cultures (n = 129).
- Urinalysis in the absence of fever (n = 86).
- Febrile infants 3 months of age or less had blood cultures (n = 49).
In some treatment centers the rate of nonrecommended tests performed was 6%, while others saw rates of 74%.
“Despite the evidence that laboratory testing rarely impacts bronchiolitis management and that bacterial infections in bronchiolitis are uncommon, our study reveals that these tests continue to be performed frequently in many parts of the world,” Dr. Zipursky and colleagues wrote in their analysis.
“Plausible reasons may include ‘automatic’ blood draws with intravenous placement, uncertainty about institutional policies, perceived need for reassurance about the diagnosis, perception of ‘doing something,’ and parental desire for a viral label,” the authors surmised. “Because parental pressure to provide interventions may be a driver of care in infants with bronchiolitis in some countries, ED clinicians need to have higher confidence in the evidence-based bronchiolitis care and convey this trust to families.”
The researchers listed among the weaknesses of their study its retrospective design, and that results from x-rays and lab tests performed were not available.
In an editorial comment accompanying the study, Joseph J. Zorc, MD, of Children’s Hospital of Philadelphia and the University of Pennsylvania in Philadelphia, noted that some of the regional differences seen in the study may be attributable to different clinical criteria used to diagnose bronchiolitis. In the United Kingdom, for example, national guidelines include the presence of crackles, while in North America guidelines focus on wheeze. “Perhaps clinicians in the United Kingdom accept the presence of crackles as an expected finding in infant with bronchiolitis and are less likely to order imaging,” Dr. Zorc said (Pediatrics. 2020 Jul 13;146[2]:e20193684).
He also pointed out that the coronavirus pandemic caused by SARS-CoV-2 (COVID- 19) could have an impact on global testing and treatment practices for bronchiolitis, as coronaviruses are a known cause of bronchiolitis. The Pediatric Emergency Research Network, comprising the 38 EDs from which Dr. Zipursky and colleagues drew their data, is conducting a prospective study looking at pediatric disease caused by SARS-CoV-2.
The “collaboration of international networks of pediatric emergency providers is an encouraging sign of potential opportunities to come ... [providing] an opportunity to evaluate variation that can lead to innovation,” Dr. Zorc concluded.
Dr. Zipursky and colleagues reported no external funding or relevant financial disclosures. Dr. Zorc reported no relevant conflicts of interest.
SOURCE: Zipursky A et al. Pediatrics. 2020 Jul 13;146(2):e2020002311.
While guidelines for bronchiolitis aim to reduce gratuitous tests and treatments, one-third of infants presenting at EDs with bronchiolitis receive an unnecessary intervention, according to a new global study.
For infants with symptoms of bronchiolitis, viral testing, blood tests, and chest x-rays are discouraged in most cases. Antibiotics are not recommended as treatment.
In a study published in Pediatrics, Amy Zipursky, MD, of the Hospital for Sick Children and the University of Toronto, and colleagues, reviewed records for 2,359 infants aged 2-11 months diagnosed with bronchiolitis during the year 2013. The data came from a network of 38 EDs in the Australia, Canada, Ireland, New Zealand, Portugal, Spain, the United Kingdom, and the United States.
Dr. Zipursky and colleagues found that, while 8% of infants in the cohort had been treated with antibiotics, 33% had received at least one nonrecommended test, with rates ranging widely across regions. In the United Kingdom and Ireland, for example, only 15% received such a test, compared with 50% in Spain and Portugal.
Of the children given antibiotics, two-thirds had suspected bacterial infections, the researchers found. Antibiotic use was highest in the United States, at 11% of infants seen for bronchiolitis, and lowest in the United Kingdom and Ireland at 4%. Administration of chest x-rays – which occurred in nearly a quarter of the cohort – increased the likelihood of antibiotics being administered (odds ratio, 2.29; 95% confidence interval, 1.62-3.24) independent of fever or severe symptoms.
The most common nonrecommended tests performed in the study were:
- Nasopharyngeal viral testing without admission to hospital (n = 591).
- Chest x-ray without ICU admission (n = 507).
- Complete blood counts (n = 222).
- Blood cultures (n = 129).
- Urinalysis in the absence of fever (n = 86).
- Febrile infants 3 months of age or less had blood cultures (n = 49).
In some treatment centers the rate of nonrecommended tests performed was 6%, while others saw rates of 74%.
“Despite the evidence that laboratory testing rarely impacts bronchiolitis management and that bacterial infections in bronchiolitis are uncommon, our study reveals that these tests continue to be performed frequently in many parts of the world,” Dr. Zipursky and colleagues wrote in their analysis.
“Plausible reasons may include ‘automatic’ blood draws with intravenous placement, uncertainty about institutional policies, perceived need for reassurance about the diagnosis, perception of ‘doing something,’ and parental desire for a viral label,” the authors surmised. “Because parental pressure to provide interventions may be a driver of care in infants with bronchiolitis in some countries, ED clinicians need to have higher confidence in the evidence-based bronchiolitis care and convey this trust to families.”
The researchers listed among the weaknesses of their study its retrospective design, and that results from x-rays and lab tests performed were not available.
In an editorial comment accompanying the study, Joseph J. Zorc, MD, of Children’s Hospital of Philadelphia and the University of Pennsylvania in Philadelphia, noted that some of the regional differences seen in the study may be attributable to different clinical criteria used to diagnose bronchiolitis. In the United Kingdom, for example, national guidelines include the presence of crackles, while in North America guidelines focus on wheeze. “Perhaps clinicians in the United Kingdom accept the presence of crackles as an expected finding in infant with bronchiolitis and are less likely to order imaging,” Dr. Zorc said (Pediatrics. 2020 Jul 13;146[2]:e20193684).
He also pointed out that the coronavirus pandemic caused by SARS-CoV-2 (COVID- 19) could have an impact on global testing and treatment practices for bronchiolitis, as coronaviruses are a known cause of bronchiolitis. The Pediatric Emergency Research Network, comprising the 38 EDs from which Dr. Zipursky and colleagues drew their data, is conducting a prospective study looking at pediatric disease caused by SARS-CoV-2.
The “collaboration of international networks of pediatric emergency providers is an encouraging sign of potential opportunities to come ... [providing] an opportunity to evaluate variation that can lead to innovation,” Dr. Zorc concluded.
Dr. Zipursky and colleagues reported no external funding or relevant financial disclosures. Dr. Zorc reported no relevant conflicts of interest.
SOURCE: Zipursky A et al. Pediatrics. 2020 Jul 13;146(2):e2020002311.
FROM PEDIATRICS
Key clinical point:
Major finding: In a global cohort, 33% of infants received at least one nonrecommended test, most commonly viral tests, chest x-rays, and blood cultures.
Study details: A retrospective cohort of 2,359 infants aged 2-11 months seen in 38 EDs in developed countries.
Disclosures: Dr. Zipursky and colleagues reported no external funding or relevant financial disclosures.
Source: Zipursky A et al. Pediatrics. 2020 Jul 13;146(2):e2020002311.