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Mandatory OSA treatment for truckers lowers insurance costs
“Among the 1.87 million U.S. commercial drivers estimated by the Bureau of Labor Statistics to be operating non–farm-based heavy trucks (gross weight at least 26,000 pounds), 17%-28%, or 318,00 to 524,000, are expected to have at least mild [obstructive sleep apnea] based on prevalence studies on commercial drivers,” wrote Stephen V. Burks, PhD, of the University of Minnesota, Morris, and colleagues.
“If the larger population of the 4.0 million drivers estimated by the Federal Motor Carrier Safety Administration to be using commercial driver’s licenses in interstate and intrastate transportation is considered, 0.68 to 1.1 million drivers may have OSA. The majority of these drivers are thought to be undiagnosed and untreated. There is thus considerable scope for healthcare cost savings through treatment of OSA among commercial drivers,” they noted.
The study was published in Sleep.
In 2017, after industry complaints about costs, the federal government withdrew its proposal to mandate testing truckers for OSA. Yet some commercial fleets do require testing, and a new study looking at retrospective data from a large fleet’s health insurance program shows that drivers diagnosed and treated for OSA saw medical cost savings, compared with those considered likely to have OSA who had neither diagnosis nor treatment.
Dr. Burks and his colleagues looked at records for 1,516 drivers tested for OSA, of whom 1,224 were positive, and compared these with an equal number of controls flagged through the same screening program as likely to have OSA, but who had never received a diagnosis in a sleep clinic or treatment with auto-adjusting positive airway pressure (APAP). All cases received auto-adjusting positive airway pressure (APAP) treatment. The investigators then looked at insurance costs for diagnosed drivers, compared with screen-positive controls before and after the polysomnogram date, over an 18-month period.
Most of the diagnosed cases in the cohort (n = 932) were deemed compliant with treatment. For every pair of subjects and controls, the researchers looked at per-member insurance costs over 18 months, though not all drivers were observed for a full period of 18 months, mostly because of turnover. Dr. Burks and colleagues found that non-OSA related medical claim costs savings after diagnosis and treatment of every 100 screen-positive controls was $153,042 (95% confidence interval, –$5,352, $330,525, P = .06.) Subjects adhering to treatment with APAP saw mean non-OSA related savings of $441 per member per month (95% CI, –$861, –$21, P = .035).
“Taken together, this is substantial evidence that OSA treatment is associated with savings in non-OSA–program medical insurance claim costs,” the authors wrote, adding that such savings could be expected to help offset expenses related to mandatory OSA programs. The authors acknowledged as a limitation of their study that it did not capture costs of pharmaceutical treatment or those of the OSA program itself. Nor did the findings capture “the value of injuries, lost work time, or disability days associated with untreated OSA, nor the savings from avoided preventable crashes.”
The study received funding from Harvard University and the National Surface Transportation Safety Center for Excellence. Two coauthors disclosed funding from pharmaceutical and device manufacturers and hold patents on sleep therapies. Another coauthor disclosed being an expert witness in trucking-related cases and one received funds from the study’s sponsor, a trucking safety research group.
SOURCE: Burks SV et al. Sleep 2019 Oct 24. doi: 10.1093/sleep/zsz262.
“Among the 1.87 million U.S. commercial drivers estimated by the Bureau of Labor Statistics to be operating non–farm-based heavy trucks (gross weight at least 26,000 pounds), 17%-28%, or 318,00 to 524,000, are expected to have at least mild [obstructive sleep apnea] based on prevalence studies on commercial drivers,” wrote Stephen V. Burks, PhD, of the University of Minnesota, Morris, and colleagues.
“If the larger population of the 4.0 million drivers estimated by the Federal Motor Carrier Safety Administration to be using commercial driver’s licenses in interstate and intrastate transportation is considered, 0.68 to 1.1 million drivers may have OSA. The majority of these drivers are thought to be undiagnosed and untreated. There is thus considerable scope for healthcare cost savings through treatment of OSA among commercial drivers,” they noted.
The study was published in Sleep.
In 2017, after industry complaints about costs, the federal government withdrew its proposal to mandate testing truckers for OSA. Yet some commercial fleets do require testing, and a new study looking at retrospective data from a large fleet’s health insurance program shows that drivers diagnosed and treated for OSA saw medical cost savings, compared with those considered likely to have OSA who had neither diagnosis nor treatment.
Dr. Burks and his colleagues looked at records for 1,516 drivers tested for OSA, of whom 1,224 were positive, and compared these with an equal number of controls flagged through the same screening program as likely to have OSA, but who had never received a diagnosis in a sleep clinic or treatment with auto-adjusting positive airway pressure (APAP). All cases received auto-adjusting positive airway pressure (APAP) treatment. The investigators then looked at insurance costs for diagnosed drivers, compared with screen-positive controls before and after the polysomnogram date, over an 18-month period.
Most of the diagnosed cases in the cohort (n = 932) were deemed compliant with treatment. For every pair of subjects and controls, the researchers looked at per-member insurance costs over 18 months, though not all drivers were observed for a full period of 18 months, mostly because of turnover. Dr. Burks and colleagues found that non-OSA related medical claim costs savings after diagnosis and treatment of every 100 screen-positive controls was $153,042 (95% confidence interval, –$5,352, $330,525, P = .06.) Subjects adhering to treatment with APAP saw mean non-OSA related savings of $441 per member per month (95% CI, –$861, –$21, P = .035).
“Taken together, this is substantial evidence that OSA treatment is associated with savings in non-OSA–program medical insurance claim costs,” the authors wrote, adding that such savings could be expected to help offset expenses related to mandatory OSA programs. The authors acknowledged as a limitation of their study that it did not capture costs of pharmaceutical treatment or those of the OSA program itself. Nor did the findings capture “the value of injuries, lost work time, or disability days associated with untreated OSA, nor the savings from avoided preventable crashes.”
The study received funding from Harvard University and the National Surface Transportation Safety Center for Excellence. Two coauthors disclosed funding from pharmaceutical and device manufacturers and hold patents on sleep therapies. Another coauthor disclosed being an expert witness in trucking-related cases and one received funds from the study’s sponsor, a trucking safety research group.
SOURCE: Burks SV et al. Sleep 2019 Oct 24. doi: 10.1093/sleep/zsz262.
“Among the 1.87 million U.S. commercial drivers estimated by the Bureau of Labor Statistics to be operating non–farm-based heavy trucks (gross weight at least 26,000 pounds), 17%-28%, or 318,00 to 524,000, are expected to have at least mild [obstructive sleep apnea] based on prevalence studies on commercial drivers,” wrote Stephen V. Burks, PhD, of the University of Minnesota, Morris, and colleagues.
“If the larger population of the 4.0 million drivers estimated by the Federal Motor Carrier Safety Administration to be using commercial driver’s licenses in interstate and intrastate transportation is considered, 0.68 to 1.1 million drivers may have OSA. The majority of these drivers are thought to be undiagnosed and untreated. There is thus considerable scope for healthcare cost savings through treatment of OSA among commercial drivers,” they noted.
The study was published in Sleep.
In 2017, after industry complaints about costs, the federal government withdrew its proposal to mandate testing truckers for OSA. Yet some commercial fleets do require testing, and a new study looking at retrospective data from a large fleet’s health insurance program shows that drivers diagnosed and treated for OSA saw medical cost savings, compared with those considered likely to have OSA who had neither diagnosis nor treatment.
Dr. Burks and his colleagues looked at records for 1,516 drivers tested for OSA, of whom 1,224 were positive, and compared these with an equal number of controls flagged through the same screening program as likely to have OSA, but who had never received a diagnosis in a sleep clinic or treatment with auto-adjusting positive airway pressure (APAP). All cases received auto-adjusting positive airway pressure (APAP) treatment. The investigators then looked at insurance costs for diagnosed drivers, compared with screen-positive controls before and after the polysomnogram date, over an 18-month period.
Most of the diagnosed cases in the cohort (n = 932) were deemed compliant with treatment. For every pair of subjects and controls, the researchers looked at per-member insurance costs over 18 months, though not all drivers were observed for a full period of 18 months, mostly because of turnover. Dr. Burks and colleagues found that non-OSA related medical claim costs savings after diagnosis and treatment of every 100 screen-positive controls was $153,042 (95% confidence interval, –$5,352, $330,525, P = .06.) Subjects adhering to treatment with APAP saw mean non-OSA related savings of $441 per member per month (95% CI, –$861, –$21, P = .035).
“Taken together, this is substantial evidence that OSA treatment is associated with savings in non-OSA–program medical insurance claim costs,” the authors wrote, adding that such savings could be expected to help offset expenses related to mandatory OSA programs. The authors acknowledged as a limitation of their study that it did not capture costs of pharmaceutical treatment or those of the OSA program itself. Nor did the findings capture “the value of injuries, lost work time, or disability days associated with untreated OSA, nor the savings from avoided preventable crashes.”
The study received funding from Harvard University and the National Surface Transportation Safety Center for Excellence. Two coauthors disclosed funding from pharmaceutical and device manufacturers and hold patents on sleep therapies. Another coauthor disclosed being an expert witness in trucking-related cases and one received funds from the study’s sponsor, a trucking safety research group.
SOURCE: Burks SV et al. Sleep 2019 Oct 24. doi: 10.1093/sleep/zsz262.
FROM SLEEP
Dupilumab effective in early- and late-onset asthma
NEW ORLEANS – A new analysis suggests
Dupilumab may be more effective in reducing severe asthma exacerbations in patients with late-onset asthma, but the drug’s effect on lung function appeared the same regardless of asthma onset. Nicola Hanania, MD, of Baylor College of Medicine in Houston presented these results at the annual meeting of the American College of Chest Physicians.
Dr. Hanania and colleagues conducted a subanalysis of the LIBERTY ASTHMA QUEST study (NCT02414854). Previous data from this study showed that patients with uncontrolled, moderate to severe asthma who received dupilumab had fewer exacerbations and better lung function than did patients who received placebo (N Engl J Med. 2018;378:2486-96).
In their subanalysis, Dr. Hanania and his colleagues evaluated the efficacy of dupilumab, given at 200 mg or 300 mg every 2 weeks, in patients with early-onset asthma (at 40 years of age or younger) and late-onset asthma (at 41 years or older). The analysis included 919 patients with early-onset asthma who received dupilumab and 450 early-onset patients who received placebo. There were 345 patients with late-onset asthma who received dupilumab and 188 late-onset patients who received placebo.
Exacerbations
Dupilumab significantly reduced the adjusted annualized severe exacerbation rates during the 52-week treatment period. Significant reductions occurred in both early- and late-onset patients, though reductions were greater in the late-onset group.
In early-onset patients, dupilumab reduced severe exacerbations by 38% when given at 200 mg and by 37% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients, dupilumab reduced exacerbations by 64% and 69%, respectively (P less than .001 vs. placebo).
Dr. Hanania said it isn’t clear why late-onset patients appear to derive more benefit with regard to exacerbations. It may be because these patients have more comorbidities or because they aren’t using their inhalers correctly. The researchers are investigating these possibilities.
Dr. Hanania went on to note that reductions in exacerbation rates were greatest in patients with elevated blood eosinophils (150 cells/mcL or greater) or fractional exhaled nitric oxide (FeNO; 25 ppb or greater).
In patients with early-onset asthma and elevated eosinophils, dupilumab reduced severe exacerbations by 50% when given at 200 mg and by 55% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated eosinophils, dupilumab reduced exacerbations by 65% and 73%, respectively (P less than .001 vs. placebo).
In patients with early-onset asthma and elevated FeNO, dupilumab reduced severe exacerbations by 56% when given at 200 mg and by 52% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated FeNO, dupilumab reduced exacerbations by 79% and 71%, respectively (P less than .001 vs. placebo).
Lung function
Dupilumab also improved prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1), compared with placebo, with similar results in early- and late-onset patients.
In early-onset patients, the P values were less than .001 for both doses of dupilumab at weeks 12 and 52. In late-onset patients, the P values were less than .001 for the 300-mg dose at week 12 and the 200-mg dose at week 52, less than .01 for the 200-mg dose at week 12, and less than .05 for the 300-mg dose at week 52.
The effects of dupilumab on pre-BD FEV1 were greatest in patients with elevated eosinophils or FeNO. At week 12, the P value was less than .001 for both doses of dupilumab in early-onset patients with elevated eosinophils or FeNO. The P value was less than .01 for both doses in late-onset patients with elevated eosinophils. And the P value was less than .001 for both doses in late-onset patients with elevated FeNO.
This research was sponsored by Sanofi and Regeneron. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.870.
NEW ORLEANS – A new analysis suggests
Dupilumab may be more effective in reducing severe asthma exacerbations in patients with late-onset asthma, but the drug’s effect on lung function appeared the same regardless of asthma onset. Nicola Hanania, MD, of Baylor College of Medicine in Houston presented these results at the annual meeting of the American College of Chest Physicians.
Dr. Hanania and colleagues conducted a subanalysis of the LIBERTY ASTHMA QUEST study (NCT02414854). Previous data from this study showed that patients with uncontrolled, moderate to severe asthma who received dupilumab had fewer exacerbations and better lung function than did patients who received placebo (N Engl J Med. 2018;378:2486-96).
In their subanalysis, Dr. Hanania and his colleagues evaluated the efficacy of dupilumab, given at 200 mg or 300 mg every 2 weeks, in patients with early-onset asthma (at 40 years of age or younger) and late-onset asthma (at 41 years or older). The analysis included 919 patients with early-onset asthma who received dupilumab and 450 early-onset patients who received placebo. There were 345 patients with late-onset asthma who received dupilumab and 188 late-onset patients who received placebo.
Exacerbations
Dupilumab significantly reduced the adjusted annualized severe exacerbation rates during the 52-week treatment period. Significant reductions occurred in both early- and late-onset patients, though reductions were greater in the late-onset group.
In early-onset patients, dupilumab reduced severe exacerbations by 38% when given at 200 mg and by 37% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients, dupilumab reduced exacerbations by 64% and 69%, respectively (P less than .001 vs. placebo).
Dr. Hanania said it isn’t clear why late-onset patients appear to derive more benefit with regard to exacerbations. It may be because these patients have more comorbidities or because they aren’t using their inhalers correctly. The researchers are investigating these possibilities.
Dr. Hanania went on to note that reductions in exacerbation rates were greatest in patients with elevated blood eosinophils (150 cells/mcL or greater) or fractional exhaled nitric oxide (FeNO; 25 ppb or greater).
In patients with early-onset asthma and elevated eosinophils, dupilumab reduced severe exacerbations by 50% when given at 200 mg and by 55% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated eosinophils, dupilumab reduced exacerbations by 65% and 73%, respectively (P less than .001 vs. placebo).
In patients with early-onset asthma and elevated FeNO, dupilumab reduced severe exacerbations by 56% when given at 200 mg and by 52% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated FeNO, dupilumab reduced exacerbations by 79% and 71%, respectively (P less than .001 vs. placebo).
Lung function
Dupilumab also improved prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1), compared with placebo, with similar results in early- and late-onset patients.
In early-onset patients, the P values were less than .001 for both doses of dupilumab at weeks 12 and 52. In late-onset patients, the P values were less than .001 for the 300-mg dose at week 12 and the 200-mg dose at week 52, less than .01 for the 200-mg dose at week 12, and less than .05 for the 300-mg dose at week 52.
The effects of dupilumab on pre-BD FEV1 were greatest in patients with elevated eosinophils or FeNO. At week 12, the P value was less than .001 for both doses of dupilumab in early-onset patients with elevated eosinophils or FeNO. The P value was less than .01 for both doses in late-onset patients with elevated eosinophils. And the P value was less than .001 for both doses in late-onset patients with elevated FeNO.
This research was sponsored by Sanofi and Regeneron. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.870.
NEW ORLEANS – A new analysis suggests
Dupilumab may be more effective in reducing severe asthma exacerbations in patients with late-onset asthma, but the drug’s effect on lung function appeared the same regardless of asthma onset. Nicola Hanania, MD, of Baylor College of Medicine in Houston presented these results at the annual meeting of the American College of Chest Physicians.
Dr. Hanania and colleagues conducted a subanalysis of the LIBERTY ASTHMA QUEST study (NCT02414854). Previous data from this study showed that patients with uncontrolled, moderate to severe asthma who received dupilumab had fewer exacerbations and better lung function than did patients who received placebo (N Engl J Med. 2018;378:2486-96).
In their subanalysis, Dr. Hanania and his colleagues evaluated the efficacy of dupilumab, given at 200 mg or 300 mg every 2 weeks, in patients with early-onset asthma (at 40 years of age or younger) and late-onset asthma (at 41 years or older). The analysis included 919 patients with early-onset asthma who received dupilumab and 450 early-onset patients who received placebo. There were 345 patients with late-onset asthma who received dupilumab and 188 late-onset patients who received placebo.
Exacerbations
Dupilumab significantly reduced the adjusted annualized severe exacerbation rates during the 52-week treatment period. Significant reductions occurred in both early- and late-onset patients, though reductions were greater in the late-onset group.
In early-onset patients, dupilumab reduced severe exacerbations by 38% when given at 200 mg and by 37% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients, dupilumab reduced exacerbations by 64% and 69%, respectively (P less than .001 vs. placebo).
Dr. Hanania said it isn’t clear why late-onset patients appear to derive more benefit with regard to exacerbations. It may be because these patients have more comorbidities or because they aren’t using their inhalers correctly. The researchers are investigating these possibilities.
Dr. Hanania went on to note that reductions in exacerbation rates were greatest in patients with elevated blood eosinophils (150 cells/mcL or greater) or fractional exhaled nitric oxide (FeNO; 25 ppb or greater).
In patients with early-onset asthma and elevated eosinophils, dupilumab reduced severe exacerbations by 50% when given at 200 mg and by 55% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated eosinophils, dupilumab reduced exacerbations by 65% and 73%, respectively (P less than .001 vs. placebo).
In patients with early-onset asthma and elevated FeNO, dupilumab reduced severe exacerbations by 56% when given at 200 mg and by 52% when given at 300 mg (P less than .001 vs. placebo). In late-onset patients with elevated FeNO, dupilumab reduced exacerbations by 79% and 71%, respectively (P less than .001 vs. placebo).
Lung function
Dupilumab also improved prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1), compared with placebo, with similar results in early- and late-onset patients.
In early-onset patients, the P values were less than .001 for both doses of dupilumab at weeks 12 and 52. In late-onset patients, the P values were less than .001 for the 300-mg dose at week 12 and the 200-mg dose at week 52, less than .01 for the 200-mg dose at week 12, and less than .05 for the 300-mg dose at week 52.
The effects of dupilumab on pre-BD FEV1 were greatest in patients with elevated eosinophils or FeNO. At week 12, the P value was less than .001 for both doses of dupilumab in early-onset patients with elevated eosinophils or FeNO. The P value was less than .01 for both doses in late-onset patients with elevated eosinophils. And the P value was less than .001 for both doses in late-onset patients with elevated FeNO.
This research was sponsored by Sanofi and Regeneron. Dr. Hanania disclosed relationships with Genentech, Novartis, AstraZeneca, Boehringer Ingelheim, GSK, Regeneron, and Sanofi.
SOURCE: Hanania N et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.870.
REPORTING FROM CHEST 2019
Collaborating in the Care of Spinal Muscular Atrophy: A Multidisciplinary Approach to Timely Screening, Diagnosis, and Management
Learn more about spinal muscular atrophy in this supplement to Pediatric News.
Click here to read.
Supplement Faculty
Claudia A. Chiriboga, MD, MPH, FAAN
(Program Chair)
Professor of Neurology and Pediatrics at CUIMC
Division of Pediatric Neurology
Columbia University Irving Medical Center
New York, NY
Diana P. Castro, MD
Assistant Professor
Pediatrics and Neurology
Neurotherapeutics
UT Southwestern Medical Center
Neurologist
Children’s Health
Dallas, TX
Mary Schroth, MD
Chief Medical Officer
Cure SMA
Elk Grove Village, IL
Charlotte J. Sumner, MD
Professor of Neurology and Neuroscience
Johns Hopkins University School of Medicine
Baltimore, MD
Kathryn J. Swoboda, MD
Katherine B. Sims, MD, Endowed Chair in Neurogenetics
Director, Neurogenetics Program
Mass General Hospital for Children
Boston, MA
Learn more about spinal muscular atrophy in this supplement to Pediatric News.
Click here to read.
Supplement Faculty
Claudia A. Chiriboga, MD, MPH, FAAN
(Program Chair)
Professor of Neurology and Pediatrics at CUIMC
Division of Pediatric Neurology
Columbia University Irving Medical Center
New York, NY
Diana P. Castro, MD
Assistant Professor
Pediatrics and Neurology
Neurotherapeutics
UT Southwestern Medical Center
Neurologist
Children’s Health
Dallas, TX
Mary Schroth, MD
Chief Medical Officer
Cure SMA
Elk Grove Village, IL
Charlotte J. Sumner, MD
Professor of Neurology and Neuroscience
Johns Hopkins University School of Medicine
Baltimore, MD
Kathryn J. Swoboda, MD
Katherine B. Sims, MD, Endowed Chair in Neurogenetics
Director, Neurogenetics Program
Mass General Hospital for Children
Boston, MA
Learn more about spinal muscular atrophy in this supplement to Pediatric News.
Click here to read.
Supplement Faculty
Claudia A. Chiriboga, MD, MPH, FAAN
(Program Chair)
Professor of Neurology and Pediatrics at CUIMC
Division of Pediatric Neurology
Columbia University Irving Medical Center
New York, NY
Diana P. Castro, MD
Assistant Professor
Pediatrics and Neurology
Neurotherapeutics
UT Southwestern Medical Center
Neurologist
Children’s Health
Dallas, TX
Mary Schroth, MD
Chief Medical Officer
Cure SMA
Elk Grove Village, IL
Charlotte J. Sumner, MD
Professor of Neurology and Neuroscience
Johns Hopkins University School of Medicine
Baltimore, MD
Kathryn J. Swoboda, MD
Katherine B. Sims, MD, Endowed Chair in Neurogenetics
Director, Neurogenetics Program
Mass General Hospital for Children
Boston, MA
Spanish risk score predicts 30-day mortality in acute HF in ED patients
Background: The MEESSI-AHF (Multiple Estimation of Risk based on the Emergency Department Spanish Score In patients with Acute Heart Failure) score is a risk-stratification tool that includes systolic blood pressure, age, NT-proBNP, potassium, cardiac troponin T, New York Heart Association class 4 disease, respiratory rate, low-output symptoms, oxygen saturation, episode associated with acute coronary syndrome, signs of left ventricular hypertrophy on EKG, creatinine, and Barthel Index Score. Prior research has shown that it accurately risk-stratified ED patients with AHF in Spain. It has not been studied in other populations.
Study design: Prospective multicenter cohort study.
Setting: Adult ED patients with acute dyspnea in four hospitals in Switzerland.
Synopsis: The study included 1,247 nonhemodialysis patients who presented to the ED with acute dyspnea, were found to have all the necessary variables to calculate the MEESSI-AHF score, and were adjudicated to have acute heart failure. The authors calculated a modified MEESSI-AHF score, excluding the Barthel Index for all patients. The authors found that a six-group modified MEESSI-AHF risk-stratification model could predict 30-day mortality with excellent discrimination (C-Statistic, 0.80). Limitations of the study include the exclusion of all hemodynamically unstable patients and those on hemodialysis.
Bottom line: The MEESSI-AHF score effectively predicts 30-day mortality in AHF in Swiss and Spanish ED patients.
Citation: Wussler D et al. External validation of the MEESSI acute heart failure risk score: A cohort study. Ann Intern Med. 2019;170:248-56.
Dr. Radhakrishnan is a hospitalist at Beth Israel Deaconess Medical Center.
Background: The MEESSI-AHF (Multiple Estimation of Risk based on the Emergency Department Spanish Score In patients with Acute Heart Failure) score is a risk-stratification tool that includes systolic blood pressure, age, NT-proBNP, potassium, cardiac troponin T, New York Heart Association class 4 disease, respiratory rate, low-output symptoms, oxygen saturation, episode associated with acute coronary syndrome, signs of left ventricular hypertrophy on EKG, creatinine, and Barthel Index Score. Prior research has shown that it accurately risk-stratified ED patients with AHF in Spain. It has not been studied in other populations.
Study design: Prospective multicenter cohort study.
Setting: Adult ED patients with acute dyspnea in four hospitals in Switzerland.
Synopsis: The study included 1,247 nonhemodialysis patients who presented to the ED with acute dyspnea, were found to have all the necessary variables to calculate the MEESSI-AHF score, and were adjudicated to have acute heart failure. The authors calculated a modified MEESSI-AHF score, excluding the Barthel Index for all patients. The authors found that a six-group modified MEESSI-AHF risk-stratification model could predict 30-day mortality with excellent discrimination (C-Statistic, 0.80). Limitations of the study include the exclusion of all hemodynamically unstable patients and those on hemodialysis.
Bottom line: The MEESSI-AHF score effectively predicts 30-day mortality in AHF in Swiss and Spanish ED patients.
Citation: Wussler D et al. External validation of the MEESSI acute heart failure risk score: A cohort study. Ann Intern Med. 2019;170:248-56.
Dr. Radhakrishnan is a hospitalist at Beth Israel Deaconess Medical Center.
Background: The MEESSI-AHF (Multiple Estimation of Risk based on the Emergency Department Spanish Score In patients with Acute Heart Failure) score is a risk-stratification tool that includes systolic blood pressure, age, NT-proBNP, potassium, cardiac troponin T, New York Heart Association class 4 disease, respiratory rate, low-output symptoms, oxygen saturation, episode associated with acute coronary syndrome, signs of left ventricular hypertrophy on EKG, creatinine, and Barthel Index Score. Prior research has shown that it accurately risk-stratified ED patients with AHF in Spain. It has not been studied in other populations.
Study design: Prospective multicenter cohort study.
Setting: Adult ED patients with acute dyspnea in four hospitals in Switzerland.
Synopsis: The study included 1,247 nonhemodialysis patients who presented to the ED with acute dyspnea, were found to have all the necessary variables to calculate the MEESSI-AHF score, and were adjudicated to have acute heart failure. The authors calculated a modified MEESSI-AHF score, excluding the Barthel Index for all patients. The authors found that a six-group modified MEESSI-AHF risk-stratification model could predict 30-day mortality with excellent discrimination (C-Statistic, 0.80). Limitations of the study include the exclusion of all hemodynamically unstable patients and those on hemodialysis.
Bottom line: The MEESSI-AHF score effectively predicts 30-day mortality in AHF in Swiss and Spanish ED patients.
Citation: Wussler D et al. External validation of the MEESSI acute heart failure risk score: A cohort study. Ann Intern Med. 2019;170:248-56.
Dr. Radhakrishnan is a hospitalist at Beth Israel Deaconess Medical Center.
Study: Pediatricians support alternative MOC assessment
two recent surveys show.
Lead author Laurel K. Leslie, MD, of Tufts University, Boston, and colleagues analyzed the perceptions of 4,238 pediatricians who participated in a pilot MOC program in 2017 and completed a fourth-quarter survey, a voluntary end-of-year survey, or both surveys. The new MOC option was developed by the American Board of Pediatrics between 2015 and 2016 as an alternative to the current proctored, closed-book general pediatrics (GP) MOC examination. The Maintenance of Certification Assessment for Pediatrics (MOCA-Peds) includes timed, multiple-choice questions delivered quarterly through a Web-based interface, provides resources to help answer questions, and yields immediate feedback, rationale, and references pertaining to answers.
Of the pediatricians surveyed, 93% considered the MOCA-Peds to be a feasible and acceptable alternative to the traditional MOC GP examination, and 89% of pediatricians indicated they would chose the MOCA-Peds model over the proctored examination, according to the study, published in Pediatrics. Of doctors who completed the quarter 4 survey, 88% agreed or strongly agreed that assessment questions aligned with the stated learning objectives, 82% agreed the questions assessed clinical judgment, 82% agreed the questions were relevant to the practice of GP, and 59% agreed the questions were relevant to their specific practice setting, according to the study. For most pediatricians surveyed, the time to answer questions was sufficient (78%).
Regarding potential anxiety associated with MOC, 89% of doctors surveyed agreed that they felt less anxiety participating in the MOCA-Peds compared with the proctored examination, and that any anxiety they felt about the MOCA-Peds lessened during the pilot as their comfort with the assessment grew (81%). When asked whether they would partake in MOCA-Peds in the future, 97% of general pediatricians and 95% of subspecialists planned to participate in MOCA-Peds to maintain their GP certification; 95% of subspecialists said they would participate in MOCA-Peds to maintain their subspecialty certification.
In a second analysis of the same study population led by Adam L. Turner, MPH, of the American Board of Pediatrics, participants were asked whether the MOCA-Peds led to any practice or knowledge changes. Nearly all (98%) respondents reported they had “learned, refreshed, or enhanced their medical knowledge” because of the assessment and 62% of pediatricians reported a practice change associated with pilot participation, according to the study, published in Pediatrics. Of those who made a practice change, 70% were general pediatricians and 41% were subspecialists.
Of the 1,727 pediatricians who positively indicated a practice change, 84% reported details about the specific change made. The most common content domains associated with a practice change included ear, nose, and throat; preventive and well-child care; and mental and behavioral health.
Within the content domains, the three most frequently cited instances in which knowledge or a practice change took place included planning the management of a child with otitis media, managing a child with an acute asthma exacerbation, and planning the management of a child with influenza. Of 400 additional responses related to practice changes beyond answers associated with a specific content domain, the three most common subthemes were using evidence-based medicine, expanding review of materials or resource use, and improving differential diagnosis. Pediatricians reported that participation in MOCA-Peds exposed them to new material and encouraged them to review guidelines or standard care protocols and their application. Respondents also reported increased review of materials or resources in practice, updating the types of resources used, and/or an increased effort to stay more updated.
Dr. Turner and associates concluded that the results “support the notion that assessment and learning can be integrated into a single platform and need not be considered mutually exclusive activities, in turn adding value for practicing physicians.”
The studies were funded by the American Board of Pediatrics Foundation. Dr. Leslie, Dr. Linda Althouse, Mr. Andrew Bradford, and Mr. Adam L. Turner are employees of The American Board of Pediatrics. Dr. Victoria Dounoucos, Dr. Murrey G. Olmsted, and Ms. Amanda C. Smith are employees of RTI International, an international nonprofit research firm with whom the board contracted to conduct this evaluation.
SOURCE: Leslie LK et al. Pediatrics. Nov. 2019 Nov. doi: 10.1542/peds.2019-2303; Turner AL et al. Pediatrics. 2019 Nov. doi: 10.1542/peds.2019-2305.
two recent surveys show.
Lead author Laurel K. Leslie, MD, of Tufts University, Boston, and colleagues analyzed the perceptions of 4,238 pediatricians who participated in a pilot MOC program in 2017 and completed a fourth-quarter survey, a voluntary end-of-year survey, or both surveys. The new MOC option was developed by the American Board of Pediatrics between 2015 and 2016 as an alternative to the current proctored, closed-book general pediatrics (GP) MOC examination. The Maintenance of Certification Assessment for Pediatrics (MOCA-Peds) includes timed, multiple-choice questions delivered quarterly through a Web-based interface, provides resources to help answer questions, and yields immediate feedback, rationale, and references pertaining to answers.
Of the pediatricians surveyed, 93% considered the MOCA-Peds to be a feasible and acceptable alternative to the traditional MOC GP examination, and 89% of pediatricians indicated they would chose the MOCA-Peds model over the proctored examination, according to the study, published in Pediatrics. Of doctors who completed the quarter 4 survey, 88% agreed or strongly agreed that assessment questions aligned with the stated learning objectives, 82% agreed the questions assessed clinical judgment, 82% agreed the questions were relevant to the practice of GP, and 59% agreed the questions were relevant to their specific practice setting, according to the study. For most pediatricians surveyed, the time to answer questions was sufficient (78%).
Regarding potential anxiety associated with MOC, 89% of doctors surveyed agreed that they felt less anxiety participating in the MOCA-Peds compared with the proctored examination, and that any anxiety they felt about the MOCA-Peds lessened during the pilot as their comfort with the assessment grew (81%). When asked whether they would partake in MOCA-Peds in the future, 97% of general pediatricians and 95% of subspecialists planned to participate in MOCA-Peds to maintain their GP certification; 95% of subspecialists said they would participate in MOCA-Peds to maintain their subspecialty certification.
In a second analysis of the same study population led by Adam L. Turner, MPH, of the American Board of Pediatrics, participants were asked whether the MOCA-Peds led to any practice or knowledge changes. Nearly all (98%) respondents reported they had “learned, refreshed, or enhanced their medical knowledge” because of the assessment and 62% of pediatricians reported a practice change associated with pilot participation, according to the study, published in Pediatrics. Of those who made a practice change, 70% were general pediatricians and 41% were subspecialists.
Of the 1,727 pediatricians who positively indicated a practice change, 84% reported details about the specific change made. The most common content domains associated with a practice change included ear, nose, and throat; preventive and well-child care; and mental and behavioral health.
Within the content domains, the three most frequently cited instances in which knowledge or a practice change took place included planning the management of a child with otitis media, managing a child with an acute asthma exacerbation, and planning the management of a child with influenza. Of 400 additional responses related to practice changes beyond answers associated with a specific content domain, the three most common subthemes were using evidence-based medicine, expanding review of materials or resource use, and improving differential diagnosis. Pediatricians reported that participation in MOCA-Peds exposed them to new material and encouraged them to review guidelines or standard care protocols and their application. Respondents also reported increased review of materials or resources in practice, updating the types of resources used, and/or an increased effort to stay more updated.
Dr. Turner and associates concluded that the results “support the notion that assessment and learning can be integrated into a single platform and need not be considered mutually exclusive activities, in turn adding value for practicing physicians.”
The studies were funded by the American Board of Pediatrics Foundation. Dr. Leslie, Dr. Linda Althouse, Mr. Andrew Bradford, and Mr. Adam L. Turner are employees of The American Board of Pediatrics. Dr. Victoria Dounoucos, Dr. Murrey G. Olmsted, and Ms. Amanda C. Smith are employees of RTI International, an international nonprofit research firm with whom the board contracted to conduct this evaluation.
SOURCE: Leslie LK et al. Pediatrics. Nov. 2019 Nov. doi: 10.1542/peds.2019-2303; Turner AL et al. Pediatrics. 2019 Nov. doi: 10.1542/peds.2019-2305.
two recent surveys show.
Lead author Laurel K. Leslie, MD, of Tufts University, Boston, and colleagues analyzed the perceptions of 4,238 pediatricians who participated in a pilot MOC program in 2017 and completed a fourth-quarter survey, a voluntary end-of-year survey, or both surveys. The new MOC option was developed by the American Board of Pediatrics between 2015 and 2016 as an alternative to the current proctored, closed-book general pediatrics (GP) MOC examination. The Maintenance of Certification Assessment for Pediatrics (MOCA-Peds) includes timed, multiple-choice questions delivered quarterly through a Web-based interface, provides resources to help answer questions, and yields immediate feedback, rationale, and references pertaining to answers.
Of the pediatricians surveyed, 93% considered the MOCA-Peds to be a feasible and acceptable alternative to the traditional MOC GP examination, and 89% of pediatricians indicated they would chose the MOCA-Peds model over the proctored examination, according to the study, published in Pediatrics. Of doctors who completed the quarter 4 survey, 88% agreed or strongly agreed that assessment questions aligned with the stated learning objectives, 82% agreed the questions assessed clinical judgment, 82% agreed the questions were relevant to the practice of GP, and 59% agreed the questions were relevant to their specific practice setting, according to the study. For most pediatricians surveyed, the time to answer questions was sufficient (78%).
Regarding potential anxiety associated with MOC, 89% of doctors surveyed agreed that they felt less anxiety participating in the MOCA-Peds compared with the proctored examination, and that any anxiety they felt about the MOCA-Peds lessened during the pilot as their comfort with the assessment grew (81%). When asked whether they would partake in MOCA-Peds in the future, 97% of general pediatricians and 95% of subspecialists planned to participate in MOCA-Peds to maintain their GP certification; 95% of subspecialists said they would participate in MOCA-Peds to maintain their subspecialty certification.
In a second analysis of the same study population led by Adam L. Turner, MPH, of the American Board of Pediatrics, participants were asked whether the MOCA-Peds led to any practice or knowledge changes. Nearly all (98%) respondents reported they had “learned, refreshed, or enhanced their medical knowledge” because of the assessment and 62% of pediatricians reported a practice change associated with pilot participation, according to the study, published in Pediatrics. Of those who made a practice change, 70% were general pediatricians and 41% were subspecialists.
Of the 1,727 pediatricians who positively indicated a practice change, 84% reported details about the specific change made. The most common content domains associated with a practice change included ear, nose, and throat; preventive and well-child care; and mental and behavioral health.
Within the content domains, the three most frequently cited instances in which knowledge or a practice change took place included planning the management of a child with otitis media, managing a child with an acute asthma exacerbation, and planning the management of a child with influenza. Of 400 additional responses related to practice changes beyond answers associated with a specific content domain, the three most common subthemes were using evidence-based medicine, expanding review of materials or resource use, and improving differential diagnosis. Pediatricians reported that participation in MOCA-Peds exposed them to new material and encouraged them to review guidelines or standard care protocols and their application. Respondents also reported increased review of materials or resources in practice, updating the types of resources used, and/or an increased effort to stay more updated.
Dr. Turner and associates concluded that the results “support the notion that assessment and learning can be integrated into a single platform and need not be considered mutually exclusive activities, in turn adding value for practicing physicians.”
The studies were funded by the American Board of Pediatrics Foundation. Dr. Leslie, Dr. Linda Althouse, Mr. Andrew Bradford, and Mr. Adam L. Turner are employees of The American Board of Pediatrics. Dr. Victoria Dounoucos, Dr. Murrey G. Olmsted, and Ms. Amanda C. Smith are employees of RTI International, an international nonprofit research firm with whom the board contracted to conduct this evaluation.
SOURCE: Leslie LK et al. Pediatrics. Nov. 2019 Nov. doi: 10.1542/peds.2019-2303; Turner AL et al. Pediatrics. 2019 Nov. doi: 10.1542/peds.2019-2305.
Researchers working to squash recurrence of superficial BCCs
LAS VEGAS – For according to Ervin H. Epstein, MD.
In a noninferiority trial, researchers in the Netherlands randomized 601 patients with superficial BCCs to one of three medical treatments: two treatments of photodynamic therapy (PDT) 1 week apart (group 1), imiquimod 5 days per week for 6 weeks with no occlusion (group 2), and 5-fluorouracil (5-FU) twice per day for 4 weeks with no occlusion (group 3). They followed the patients for 5 years to see which tumors came back (J Invest Dermatol. 2018 Mar;138[3]:527-33). At 5 years, tumor-free survival was 63% in group 1, 81% in group 2, and 70% in group 3. Based on this analysis the authors concluded that imiquimod is the first choice for noninvasive treatment of most primary BCCs.
“Yes, imiquimod is helpful, but it’s not as good as surgery,” Dr. Epstein said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Researchers like Dr. Epstein, a dermatologist at Brown & Toland Physicians in Oakland, Calif., have been exploring ways to reduce the recurrence of BCCs in those at high risk. One approach is to stay out of the sun, but that is not practical for most people, “and the data are not very supportive,” he said. “Very few people can actually avoid sunlight. What about topical 5-FU? Suppose you put on 5-FU and then study people for the next year, to see what the likelihood is of them getting a BCC? Why it has taken us so long to do this kind of study is in some ways shameful.” He mentioned one study in which patients at risk of superficial BCC recurrence applied topical 5-FU twice a day for 2-4 weeks. The regimen led to an 11% decrease in the development of BCCs, a trend that did not reach statistical significance.
Another approach to warding off BCC recurrence is to take oral hedgehog pathway inhibitors, which are highly effective. “The problem is, hedgehog pathway inhibitors have side effects that are not catastrophic, but they’re annoying,” Dr. Epstein said. “Patients can lose their hair, they get muscle cramps, and can lose their taste.”
To date, there have been at least three trials evaluating the feasibility of a topical hedgehog pathway inhibitor in adult subjects. In one of the trials, researchers evaluated the efficacy of LDE225, a selective antagonist of Smoothened, in eight patients with nevoid basal cell carcinoma syndrome. They were instructed to apply LDE225 twice per day for 4 weeks (J Invest Dermatol 2011 Aug;131[8]:1735-44). Of 13 BCCs treated in the patients, 12 had a partial to complete response. In fact, eight BCCs had an average of 56% volume reduction but none had complete histologic clearing.
At PellePharm, a biotechnology that Dr. Epstein cofounded, researchers are developing patidegib topical gel, 2%, for the reduction of disease burden of persistently developing BCCs in subjects with Gorlin syndrome. In a phase 3 trial, which just completed recruitment, adults are instructed to apply the gel twice daily to the face for 12 months. The primary endpoint is a comparison between the two treatment arms of the number of new surgically eligible BCCs that develop over the 12-month period. “We want to see if we can reduce the number of surgically eligible BCCs,” Dr. Epstein said. “We’re very hopeful.”
SDEF and this news organization are owned by the same parent company. Dr. Epstein spoke during a forum on cutaneous malignancies at the meeting.
Dr. Epstein disclosed that he has been a consultant for Genentech, Novartis, Amgen, and Infinity. He is also cofounder/director and stockholder in PellePharm.
LAS VEGAS – For according to Ervin H. Epstein, MD.
In a noninferiority trial, researchers in the Netherlands randomized 601 patients with superficial BCCs to one of three medical treatments: two treatments of photodynamic therapy (PDT) 1 week apart (group 1), imiquimod 5 days per week for 6 weeks with no occlusion (group 2), and 5-fluorouracil (5-FU) twice per day for 4 weeks with no occlusion (group 3). They followed the patients for 5 years to see which tumors came back (J Invest Dermatol. 2018 Mar;138[3]:527-33). At 5 years, tumor-free survival was 63% in group 1, 81% in group 2, and 70% in group 3. Based on this analysis the authors concluded that imiquimod is the first choice for noninvasive treatment of most primary BCCs.
“Yes, imiquimod is helpful, but it’s not as good as surgery,” Dr. Epstein said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Researchers like Dr. Epstein, a dermatologist at Brown & Toland Physicians in Oakland, Calif., have been exploring ways to reduce the recurrence of BCCs in those at high risk. One approach is to stay out of the sun, but that is not practical for most people, “and the data are not very supportive,” he said. “Very few people can actually avoid sunlight. What about topical 5-FU? Suppose you put on 5-FU and then study people for the next year, to see what the likelihood is of them getting a BCC? Why it has taken us so long to do this kind of study is in some ways shameful.” He mentioned one study in which patients at risk of superficial BCC recurrence applied topical 5-FU twice a day for 2-4 weeks. The regimen led to an 11% decrease in the development of BCCs, a trend that did not reach statistical significance.
Another approach to warding off BCC recurrence is to take oral hedgehog pathway inhibitors, which are highly effective. “The problem is, hedgehog pathway inhibitors have side effects that are not catastrophic, but they’re annoying,” Dr. Epstein said. “Patients can lose their hair, they get muscle cramps, and can lose their taste.”
To date, there have been at least three trials evaluating the feasibility of a topical hedgehog pathway inhibitor in adult subjects. In one of the trials, researchers evaluated the efficacy of LDE225, a selective antagonist of Smoothened, in eight patients with nevoid basal cell carcinoma syndrome. They were instructed to apply LDE225 twice per day for 4 weeks (J Invest Dermatol 2011 Aug;131[8]:1735-44). Of 13 BCCs treated in the patients, 12 had a partial to complete response. In fact, eight BCCs had an average of 56% volume reduction but none had complete histologic clearing.
At PellePharm, a biotechnology that Dr. Epstein cofounded, researchers are developing patidegib topical gel, 2%, for the reduction of disease burden of persistently developing BCCs in subjects with Gorlin syndrome. In a phase 3 trial, which just completed recruitment, adults are instructed to apply the gel twice daily to the face for 12 months. The primary endpoint is a comparison between the two treatment arms of the number of new surgically eligible BCCs that develop over the 12-month period. “We want to see if we can reduce the number of surgically eligible BCCs,” Dr. Epstein said. “We’re very hopeful.”
SDEF and this news organization are owned by the same parent company. Dr. Epstein spoke during a forum on cutaneous malignancies at the meeting.
Dr. Epstein disclosed that he has been a consultant for Genentech, Novartis, Amgen, and Infinity. He is also cofounder/director and stockholder in PellePharm.
LAS VEGAS – For according to Ervin H. Epstein, MD.
In a noninferiority trial, researchers in the Netherlands randomized 601 patients with superficial BCCs to one of three medical treatments: two treatments of photodynamic therapy (PDT) 1 week apart (group 1), imiquimod 5 days per week for 6 weeks with no occlusion (group 2), and 5-fluorouracil (5-FU) twice per day for 4 weeks with no occlusion (group 3). They followed the patients for 5 years to see which tumors came back (J Invest Dermatol. 2018 Mar;138[3]:527-33). At 5 years, tumor-free survival was 63% in group 1, 81% in group 2, and 70% in group 3. Based on this analysis the authors concluded that imiquimod is the first choice for noninvasive treatment of most primary BCCs.
“Yes, imiquimod is helpful, but it’s not as good as surgery,” Dr. Epstein said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.
Researchers like Dr. Epstein, a dermatologist at Brown & Toland Physicians in Oakland, Calif., have been exploring ways to reduce the recurrence of BCCs in those at high risk. One approach is to stay out of the sun, but that is not practical for most people, “and the data are not very supportive,” he said. “Very few people can actually avoid sunlight. What about topical 5-FU? Suppose you put on 5-FU and then study people for the next year, to see what the likelihood is of them getting a BCC? Why it has taken us so long to do this kind of study is in some ways shameful.” He mentioned one study in which patients at risk of superficial BCC recurrence applied topical 5-FU twice a day for 2-4 weeks. The regimen led to an 11% decrease in the development of BCCs, a trend that did not reach statistical significance.
Another approach to warding off BCC recurrence is to take oral hedgehog pathway inhibitors, which are highly effective. “The problem is, hedgehog pathway inhibitors have side effects that are not catastrophic, but they’re annoying,” Dr. Epstein said. “Patients can lose their hair, they get muscle cramps, and can lose their taste.”
To date, there have been at least three trials evaluating the feasibility of a topical hedgehog pathway inhibitor in adult subjects. In one of the trials, researchers evaluated the efficacy of LDE225, a selective antagonist of Smoothened, in eight patients with nevoid basal cell carcinoma syndrome. They were instructed to apply LDE225 twice per day for 4 weeks (J Invest Dermatol 2011 Aug;131[8]:1735-44). Of 13 BCCs treated in the patients, 12 had a partial to complete response. In fact, eight BCCs had an average of 56% volume reduction but none had complete histologic clearing.
At PellePharm, a biotechnology that Dr. Epstein cofounded, researchers are developing patidegib topical gel, 2%, for the reduction of disease burden of persistently developing BCCs in subjects with Gorlin syndrome. In a phase 3 trial, which just completed recruitment, adults are instructed to apply the gel twice daily to the face for 12 months. The primary endpoint is a comparison between the two treatment arms of the number of new surgically eligible BCCs that develop over the 12-month period. “We want to see if we can reduce the number of surgically eligible BCCs,” Dr. Epstein said. “We’re very hopeful.”
SDEF and this news organization are owned by the same parent company. Dr. Epstein spoke during a forum on cutaneous malignancies at the meeting.
Dr. Epstein disclosed that he has been a consultant for Genentech, Novartis, Amgen, and Infinity. He is also cofounder/director and stockholder in PellePharm.
EXPERT ANALYSIS FROM THE SDEF LAS VEGAS DERMATOLOGY SEMINAR
Oral JAK1/2 inhibitor promising in alopecia areata
MADRID – In a phase 2, dose-ranging study, 78% of patients with long-standing moderate or severe alopecia areata rated their condition as “much improved” or “very much improved” after 24 weeks on the top dose of an investigational oral selective Janus kinase 1 and 2 (JAK1/2) inhibitor, compared with 21% of placebo-treated controls, James V. Cassella, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The primary study endpoint – at least a 50% reduction in the Severity of Alopecia Tool (SALT) score between baseline and 24 weeks – was achieved in 58% of patients on the JAK1/2 inhibitor (known for now as CTP-543) at 12 mg twice a day, 47% of those on CTP-543 at 8 mg twice a day, 21% on 4 mg twice a day, and in 9% of controls on placebo in the double-blind randomized trial. The 4-mg twice-daily dosing will not move on to phase 3 studies because of its demonstrated lack of efficacy, according to Dr. Cassella, chief development officer at Concert Pharmaceuticals, the study sponsor.
The study included 149 adults whose current episode of alopecia areata was of 3-6 years’ duration, with an average lifetime 15-year history of active disease. Their average baseline score on the 0-100 SALT scale was in the upper 80s, indicative of 80% or greater hair loss.
A SALT 75 response, meaning at least a 75% reduction in SALT score from baseline, was achieved in a dose-dependent fashion: In 42% of patients at the top dose of CTP-543, 29% of those on 8 mg twice a day, 14% with 4 mg twice a day, and in 7% of controls. An even more rigorous SALT 90 response was attained in 36%, 16%, 2%, and no controls, respectively.
The 12-mg twice-daily dosing produced faster onset and greater magnitude of response than did the 8-mg twice-daily dosing, but this dose-ranging study is not the final word on that score, according to Dr. Cassella.
“Week 24 is not a magic number,” he said. “The slope of the efficacy line for 8 mg [twice a day] looked like it was still going up at week 24, and the 12-mg BID curve hadn’t completely plateaued. Those are things we will consider for the future in terms of long-term trials.”
Changes in the eyebrows and lashes weren’t formally assessed in this study, although they will be in future trials. Anecdotally, however, patients with alopecia areata at those sites typically experienced complete or nearly complete regrowth in response to the higher doses of CTP-543, he said.
Safety-wise, there was no trend for increased adverse events with increasing doses of CTP-543. The observed treatment side effects were those typical of JAK inhibitors as a class effect, mainly headache, nasopharyngitis, upper respiratory infections, and new-onset acne. In terms of hematologic findings of special interest, there was one case of reversible neutropenia in the control group and another in the 8-mg twice-daily group, which resolved upon temporary suspension of treatment.
“Nothing surprising to us, and nothing very serious,” Dr. Cassella said.
Most patients in the 12-mg twice daily group have enrolled in an ongoing long-term extension study. In addition, two phase 2 studies are ongoing, with a focus on once-daily versus twice-daily dosing at 8 mg or 12 mg. Phase 3 studies are in the planning stage, he added.
The phase 2 dose-ranging study was sponsored by Concert Pharmaceuticals.
CTP-543 is one of an array of oral JAK inhibitors now in the developmental pipeline for alopecia areata, a severe, psychosocially devastating disease for which at present there is no Food and Drug Administration–approved therapy.
MADRID – In a phase 2, dose-ranging study, 78% of patients with long-standing moderate or severe alopecia areata rated their condition as “much improved” or “very much improved” after 24 weeks on the top dose of an investigational oral selective Janus kinase 1 and 2 (JAK1/2) inhibitor, compared with 21% of placebo-treated controls, James V. Cassella, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The primary study endpoint – at least a 50% reduction in the Severity of Alopecia Tool (SALT) score between baseline and 24 weeks – was achieved in 58% of patients on the JAK1/2 inhibitor (known for now as CTP-543) at 12 mg twice a day, 47% of those on CTP-543 at 8 mg twice a day, 21% on 4 mg twice a day, and in 9% of controls on placebo in the double-blind randomized trial. The 4-mg twice-daily dosing will not move on to phase 3 studies because of its demonstrated lack of efficacy, according to Dr. Cassella, chief development officer at Concert Pharmaceuticals, the study sponsor.
The study included 149 adults whose current episode of alopecia areata was of 3-6 years’ duration, with an average lifetime 15-year history of active disease. Their average baseline score on the 0-100 SALT scale was in the upper 80s, indicative of 80% or greater hair loss.
A SALT 75 response, meaning at least a 75% reduction in SALT score from baseline, was achieved in a dose-dependent fashion: In 42% of patients at the top dose of CTP-543, 29% of those on 8 mg twice a day, 14% with 4 mg twice a day, and in 7% of controls. An even more rigorous SALT 90 response was attained in 36%, 16%, 2%, and no controls, respectively.
The 12-mg twice-daily dosing produced faster onset and greater magnitude of response than did the 8-mg twice-daily dosing, but this dose-ranging study is not the final word on that score, according to Dr. Cassella.
“Week 24 is not a magic number,” he said. “The slope of the efficacy line for 8 mg [twice a day] looked like it was still going up at week 24, and the 12-mg BID curve hadn’t completely plateaued. Those are things we will consider for the future in terms of long-term trials.”
Changes in the eyebrows and lashes weren’t formally assessed in this study, although they will be in future trials. Anecdotally, however, patients with alopecia areata at those sites typically experienced complete or nearly complete regrowth in response to the higher doses of CTP-543, he said.
Safety-wise, there was no trend for increased adverse events with increasing doses of CTP-543. The observed treatment side effects were those typical of JAK inhibitors as a class effect, mainly headache, nasopharyngitis, upper respiratory infections, and new-onset acne. In terms of hematologic findings of special interest, there was one case of reversible neutropenia in the control group and another in the 8-mg twice-daily group, which resolved upon temporary suspension of treatment.
“Nothing surprising to us, and nothing very serious,” Dr. Cassella said.
Most patients in the 12-mg twice daily group have enrolled in an ongoing long-term extension study. In addition, two phase 2 studies are ongoing, with a focus on once-daily versus twice-daily dosing at 8 mg or 12 mg. Phase 3 studies are in the planning stage, he added.
The phase 2 dose-ranging study was sponsored by Concert Pharmaceuticals.
CTP-543 is one of an array of oral JAK inhibitors now in the developmental pipeline for alopecia areata, a severe, psychosocially devastating disease for which at present there is no Food and Drug Administration–approved therapy.
MADRID – In a phase 2, dose-ranging study, 78% of patients with long-standing moderate or severe alopecia areata rated their condition as “much improved” or “very much improved” after 24 weeks on the top dose of an investigational oral selective Janus kinase 1 and 2 (JAK1/2) inhibitor, compared with 21% of placebo-treated controls, James V. Cassella, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The primary study endpoint – at least a 50% reduction in the Severity of Alopecia Tool (SALT) score between baseline and 24 weeks – was achieved in 58% of patients on the JAK1/2 inhibitor (known for now as CTP-543) at 12 mg twice a day, 47% of those on CTP-543 at 8 mg twice a day, 21% on 4 mg twice a day, and in 9% of controls on placebo in the double-blind randomized trial. The 4-mg twice-daily dosing will not move on to phase 3 studies because of its demonstrated lack of efficacy, according to Dr. Cassella, chief development officer at Concert Pharmaceuticals, the study sponsor.
The study included 149 adults whose current episode of alopecia areata was of 3-6 years’ duration, with an average lifetime 15-year history of active disease. Their average baseline score on the 0-100 SALT scale was in the upper 80s, indicative of 80% or greater hair loss.
A SALT 75 response, meaning at least a 75% reduction in SALT score from baseline, was achieved in a dose-dependent fashion: In 42% of patients at the top dose of CTP-543, 29% of those on 8 mg twice a day, 14% with 4 mg twice a day, and in 7% of controls. An even more rigorous SALT 90 response was attained in 36%, 16%, 2%, and no controls, respectively.
The 12-mg twice-daily dosing produced faster onset and greater magnitude of response than did the 8-mg twice-daily dosing, but this dose-ranging study is not the final word on that score, according to Dr. Cassella.
“Week 24 is not a magic number,” he said. “The slope of the efficacy line for 8 mg [twice a day] looked like it was still going up at week 24, and the 12-mg BID curve hadn’t completely plateaued. Those are things we will consider for the future in terms of long-term trials.”
Changes in the eyebrows and lashes weren’t formally assessed in this study, although they will be in future trials. Anecdotally, however, patients with alopecia areata at those sites typically experienced complete or nearly complete regrowth in response to the higher doses of CTP-543, he said.
Safety-wise, there was no trend for increased adverse events with increasing doses of CTP-543. The observed treatment side effects were those typical of JAK inhibitors as a class effect, mainly headache, nasopharyngitis, upper respiratory infections, and new-onset acne. In terms of hematologic findings of special interest, there was one case of reversible neutropenia in the control group and another in the 8-mg twice-daily group, which resolved upon temporary suspension of treatment.
“Nothing surprising to us, and nothing very serious,” Dr. Cassella said.
Most patients in the 12-mg twice daily group have enrolled in an ongoing long-term extension study. In addition, two phase 2 studies are ongoing, with a focus on once-daily versus twice-daily dosing at 8 mg or 12 mg. Phase 3 studies are in the planning stage, he added.
The phase 2 dose-ranging study was sponsored by Concert Pharmaceuticals.
CTP-543 is one of an array of oral JAK inhibitors now in the developmental pipeline for alopecia areata, a severe, psychosocially devastating disease for which at present there is no Food and Drug Administration–approved therapy.
REPORTING FROM THE EADV CONGRESS
Sunitinib for mRCC: Real-world experience differs somewhat
First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.
Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.
The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.
Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.
The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.
Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.
“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.
Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.
At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.
Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.
SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.
First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.
Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.
The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.
Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.
The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.
Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.
“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.
Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.
At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.
Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.
SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.
First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.
Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.
The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.
Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.
The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.
Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.
“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.
Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.
At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.
Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.
SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.
FROM THE JOURNAL OF GLOBAL ONCOLOGY
Supplemental oxygen: More isn’t always better
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
PRACTICE CHANGER
Do not use liberal oxygen therapy (SpO2 > 96%) in acutely ill adults, as it is associated with increased all-cause mortality.1
STRENGTH OF RECOMMENDATION
A: Based on a systematic review and meta-analysis of 25 randomized controlled trials.
Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
45-year-old woman • fever and chills • diffuse abdominal pain • shortness of breath • Dx?
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
