Pulmonology

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

A 39-year-old woman presented to the emergency department with a 2-day history of exertional dyspnea, left-sided chest pain with pleuritic characteristics, and cough without fever or chills. She had a history of severe postprandial nausea and vomiting, weight loss, and malnutrition, which had necessitated placement of a peripherally inserted central catheter in her right arm for total parenteral nutrition.

On physical examination, the patient was afebrile but tachycardic and tachypneic. Her oxygen saturation on room air by pulse oximetry was 91%, though she was not in significant distress. Breath sounds were equal bilaterally and clear, with symmetrical chest wall expansion.

Her white blood cell count was 18.5 × 10⁹/L (reference range 3.5–10.5), with 19.3% eosinophils (reference range 1%–7%); her D-dimer level was also elevated.

Conditions to consider in a patient with these imaging findings in the setting of leukocytosis and eosinophilia include mycobacterial infection, hypersensitivity reaction, diffuse fungal infiltrates, and possibly metastatic disease such as thyroid carcinoma or melanoma. The patient reported having had a purified protein derivative test that was positive for tuberculosis, but she denied having had active disease.

She underwent bronchosocopy. Bronchoalveolar lavage specimen study showed an elevated eosinophil count of 17%. Acid-fast staining detected no organisms. Transbronchial biopsy study revealed foreign-body granulomas from microcrystalline cellulose microemboli deposited in the microvasculature of the patient’s lungs. Upon further questioning the patient admitted she had crushed oral tablets of prescribed opioids and injected them intravenously.

A COMPLICATION OF INJECTING ORAL TABLETS

Oral tablets typically contain talc, cellulose, cornstarch, or combinations of these substances as binding agents. When pulverized, the powder can be combined with water to form an injectable solution with higher and more rapid bioavailability.^1,2 The binders, however, are insoluble and accumulate in various tissues.

Intravenous injection of microcellulose has been shown to produce pulmonary and peripheral eosinophilia in birds. In humans, the immune response in foreign body granulomatosis can vary, and case reports have not mentioned eosinophils in the lungs or serum.^3,4

Deposition of these particles in pulmonary vessels is common and can trigger a potentially fatal reaction, presenting as acute onset of cough, chest pain, dyspnea, fever, and pulmonary hypertension. The severity of these clinical findings is relative to the degree of pulmonary hypertension created by the arteriolar involvement of these emboli.^2,5

Our patient’s exertional dyspnea and hypoxemia resolved during 1 week of hospitalization with conservative management and supplemental oxygen. She was referred to our pain rehabilitation clinic, where she was successfully weaned from narcotics. Her pulmonary findings on computed tomography were still present 3 years after her initial images, though less prominent.

A 39-year-old woman presented to the emergency department with a 2-day history of exertional dyspnea, left-sided chest pain with pleuritic characteristics, and cough without fever or chills. She had a history of severe postprandial nausea and vomiting, weight loss, and malnutrition, which had necessitated placement of a peripherally inserted central catheter in her right arm for total parenteral nutrition.

On physical examination, the patient was afebrile but tachycardic and tachypneic. Her oxygen saturation on room air by pulse oximetry was 91%, though she was not in significant distress. Breath sounds were equal bilaterally and clear, with symmetrical chest wall expansion.

Her white blood cell count was 18.5 × 10⁹/L (reference range 3.5–10.5), with 19.3% eosinophils (reference range 1%–7%); her D-dimer level was also elevated.

Conditions to consider in a patient with these imaging findings in the setting of leukocytosis and eosinophilia include mycobacterial infection, hypersensitivity reaction, diffuse fungal infiltrates, and possibly metastatic disease such as thyroid carcinoma or melanoma. The patient reported having had a purified protein derivative test that was positive for tuberculosis, but she denied having had active disease.

She underwent bronchosocopy. Bronchoalveolar lavage specimen study showed an elevated eosinophil count of 17%. Acid-fast staining detected no organisms. Transbronchial biopsy study revealed foreign-body granulomas from microcrystalline cellulose microemboli deposited in the microvasculature of the patient’s lungs. Upon further questioning the patient admitted she had crushed oral tablets of prescribed opioids and injected them intravenously.

A COMPLICATION OF INJECTING ORAL TABLETS

Oral tablets typically contain talc, cellulose, cornstarch, or combinations of these substances as binding agents. When pulverized, the powder can be combined with water to form an injectable solution with higher and more rapid bioavailability.^1,2 The binders, however, are insoluble and accumulate in various tissues.

Intravenous injection of microcellulose has been shown to produce pulmonary and peripheral eosinophilia in birds. In humans, the immune response in foreign body granulomatosis can vary, and case reports have not mentioned eosinophils in the lungs or serum.^3,4

Deposition of these particles in pulmonary vessels is common and can trigger a potentially fatal reaction, presenting as acute onset of cough, chest pain, dyspnea, fever, and pulmonary hypertension. The severity of these clinical findings is relative to the degree of pulmonary hypertension created by the arteriolar involvement of these emboli.^2,5

Our patient’s exertional dyspnea and hypoxemia resolved during 1 week of hospitalization with conservative management and supplemental oxygen. She was referred to our pain rehabilitation clinic, where she was successfully weaned from narcotics. Her pulmonary findings on computed tomography were still present 3 years after her initial images, though less prominent.

A 39-year-old woman presented to the emergency department with a 2-day history of exertional dyspnea, left-sided chest pain with pleuritic characteristics, and cough without fever or chills. She had a history of severe postprandial nausea and vomiting, weight loss, and malnutrition, which had necessitated placement of a peripherally inserted central catheter in her right arm for total parenteral nutrition.

On physical examination, the patient was afebrile but tachycardic and tachypneic. Her oxygen saturation on room air by pulse oximetry was 91%, though she was not in significant distress. Breath sounds were equal bilaterally and clear, with symmetrical chest wall expansion.

Her white blood cell count was 18.5 × 10⁹/L (reference range 3.5–10.5), with 19.3% eosinophils (reference range 1%–7%); her D-dimer level was also elevated.

Conditions to consider in a patient with these imaging findings in the setting of leukocytosis and eosinophilia include mycobacterial infection, hypersensitivity reaction, diffuse fungal infiltrates, and possibly metastatic disease such as thyroid carcinoma or melanoma. The patient reported having had a purified protein derivative test that was positive for tuberculosis, but she denied having had active disease.

She underwent bronchosocopy. Bronchoalveolar lavage specimen study showed an elevated eosinophil count of 17%. Acid-fast staining detected no organisms. Transbronchial biopsy study revealed foreign-body granulomas from microcrystalline cellulose microemboli deposited in the microvasculature of the patient’s lungs. Upon further questioning the patient admitted she had crushed oral tablets of prescribed opioids and injected them intravenously.

A COMPLICATION OF INJECTING ORAL TABLETS

Oral tablets typically contain talc, cellulose, cornstarch, or combinations of these substances as binding agents. When pulverized, the powder can be combined with water to form an injectable solution with higher and more rapid bioavailability.^1,2 The binders, however, are insoluble and accumulate in various tissues.

Intravenous injection of microcellulose has been shown to produce pulmonary and peripheral eosinophilia in birds. In humans, the immune response in foreign body granulomatosis can vary, and case reports have not mentioned eosinophils in the lungs or serum.^3,4

Deposition of these particles in pulmonary vessels is common and can trigger a potentially fatal reaction, presenting as acute onset of cough, chest pain, dyspnea, fever, and pulmonary hypertension. The severity of these clinical findings is relative to the degree of pulmonary hypertension created by the arteriolar involvement of these emboli.^2,5

Our patient’s exertional dyspnea and hypoxemia resolved during 1 week of hospitalization with conservative management and supplemental oxygen. She was referred to our pain rehabilitation clinic, where she was successfully weaned from narcotics. Her pulmonary findings on computed tomography were still present 3 years after her initial images, though less prominent.

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

In the Clinical Inquiry, “Does prophylactic azithromycin reduce the number of COPD exacerbations or hospitalizations?” (J Fam Pract. 2018;67:384-385), Lyon et al state that azithromycin “doesn’t benefit patients ≤65 years, patients with GOLD [Global Initiative for Obstructive Lung Disease] stage IV COPD [chronic obstructive pulmonary disease], current smokers, or patients not using oxygen (strength of recommendation [SOR]: B, randomized controlled trials [RCTs]).” These categorical statements are misleading, and clinicians should ignore most of them when considering azithromycin for their patients with severe COPD.

It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years.

The authors cited groups that were identified in a posthoc analysis¹ of the only large trial involving azithromycin for the treatment of COPD to date.²P values for the interaction of azithromycin with GOLD stage (P=.04), smoking (P=.03), and age (P=.02) were significant, but the mean effects (hazard ratios [HRs]) for GOLD stage IV, smoking, and age ≤65 were .84, .99, and .84, respectively. It would be more accurate to say that there may be a diminished efficacy of azithromycin for patients with GOLD IV COPD and age ≤65 years. Only smokers appear to show no response, although the lower end of the 95% confidence interval was 0.71. The P value for the interaction of azithromycin with no long-term oxygen use (P=.23) was not significant, and it is incorrect to infer that oxygen use or nonuse predicts response.

The authors correctly state that the “significance of the results is limited because the study was not originally powered for this level of subgroup analysis,” but this statement is buried later in the article.

David L. Hahn, MD, MS
Madison, Wis

1. Han MK, Tayob N, Murray S, et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am J Respir Crit Care Med. 2014;189:1503-1508.

2. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.

Continue to: Author's response...

Author’s response:

Your statement that the evidence-based answer regarding the lack of benefit of azithromycin in patients ≤65 years of age, with stage IV COPD, current smokers, and patients not using oxygen is “misleading” is a bit of an overstatement.

It is fair to say, however, that our statement regarding lack of efficacy among these subgroups of patients should be softened a bit since the data are from subgroup analyses, which should never be the source of definitive conclusions. And you point out that the 95% confidence intervals [CIs] of the HRs for these subgroups of patients do not include a potentially significant effect (0.68, 0.71, 0.61, and 0.65, respectively), so it is possible there is a Type II error, which would lead one to conclude there is no effect for these subgroups when there is one.

Regarding oxygen therapy, in this Clinical Inquiry, we presented data from the direct subgroup analysis, which revealed no difference in COPD exacerbations between the azithromycin and placebo groups for patients not receiving long-term supplemental oxygen (HR=0.80; 95% CI, 0.62-1.03); however, you are correct to point out that the oxygen use subgroup interaction (patients on oxygen vs patients not on oxygen), which we did not include in this Clinical Inquiry, did not reach significance (P=.23), casting some doubt on the authors’ conclusion of no effect for patients not on oxygen.

On the whole, I feel this Clinical Inquiry accurately summarized the existing evidence and that additional research is needed to better define the utility of azithromycin in these subgroups of patients.

Corey Lyon, DO
Denver, Colo

ILLUSTRATIVE CASE

A 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

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 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

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 63-year-old woman with a history of hypertension presents to the emergency department (ED) with acute onset shortness of breath and pleuritic chest pain after traveling across the country for a work conference. She has no history of cancer, liver disease, or renal disease. Her blood pressure is 140/80 mm Hg, and her heart rate is 90 bpm. You diagnose an acute PE in this patient and start anticoagulation. Should you admit her to the hospital to decrease morbidity and mortality?

According to the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects approximately 900,000 people each year, and approximately 60,000 to 100,000 of these patients die annually.² Pulmonary embolism is the third leading cause of death from cardiovascular disease, following heart attacks and strokes.³ Prompt diagnosis and treatment with systemic anticoagulation improves patient outcomes and decreases the risk of long-term complications.

The 2016 American College of Chest Physicians (CHEST) guideline on antithrombotic therapy for VTE disease recommends home treatment or early discharge over standard discharge (after the first 5 days of treatment) for patients who meet the following clinical criteria: “clinically stable with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal or liver disease, or severe thrombocytopenia (ie, <70,000/mm³); expected to be compliant with treatment; and the patient feels well enough to be treated at home.”³

The guideline states that various clinical decision tools, such as the Pulmonary Embolism Severity Index (PESI), can aid in identifying low-risk patients to be considered for treatment at home. The PESI uses age, gender, vital signs, mental status, and a history of cancer, lung, and cardiac disease to stratify patients by risk.⁴

A systematic review of 1 randomized controlled trial (RCT) and 7 observational studies found that in low-risk patients, outpatient treatment was as safe as inpatient treatment.⁵ This more recent study determines the net clinical benefit of hospitalized vs outpatient management in a wider range of patients with acute PE, regardless of initial risk.¹

STUDY SUMMARY

Hospitalization confers no benefit to stable patients with acute PE

This retrospective, propensity-matched cohort study compared rates of adverse events in 1127 patients with acute PE managed in the hospital vs outpatient setting.¹ Patients were classified as outpatients if they were discharged from the ED or discharged from the hospital within 48 hours of admission. Patients were included if a symptomatic acute PE was diagnosed via computed tomography scan or high-probability ventilation-perfusion scan and excluded if they were <19 years of age, diagnosed with a PE during hospitalization, had chronic PE, or were hemodynamically unstable, among other factors. The investigators calculated PESI scores for all patients.

This trial supports guideline recommendations to manage hemodynamically stable patients with acute PE as outpatients.

Propensity scores matched patients on 28 patient characteristics and known risk factors for adverse events to ensure the groups were similar. The primary outcome was rate of adverse events, including recurrent VTE, major bleeding, or death at 14 days. The secondary outcome was rates of the above during the 3-month follow-up period.

Continue to: Of the 1127 eligible patients...

Of the 1127 eligible patients, 1081 were included in the matched cohort, with 576 (53%) treated as hospitalized patients and 505 (47%) treated as outpatients. The mean age of the matched cohorts was 63.2 years for the inpatient group and 63.6 years for the outpatient group. Overall, the cohorts were well matched.

The 14-day rate of adverse events was higher in hospitalized patients than in outpatients (13% vs 3.3%; odds ratio [OR] = 5.07; 95% confidence interval [CI], 1.68-15.28), with each of the adverse events that made up the primary outcome occurring more frequently in the hospitalized group (TABLE). The rate of adverse events at 3 months was also greater for hospitalized patients compared with outpatients (21.7% vs 6.9%; OR = 4.9; 95% CI, 2.62-9.17). The results remained similar for high-risk patients (Class III-V) based on their PESI score.

WHAT’S NEW

A higher rate of AEs in those treated as inpatients vs outpatients

This trial supports the CHEST guideline recommendations³ to manage hemodynamically stable patients with acute PE as outpatients. It adds to the conversation by demonstrating higher rates of adverse events with hospitalization, even in high-risk subgroups (PESI Class III-V).

CAVEATS

A good study, but it wasn’t an RCT

While this is a well-designed cohort study, it is not a randomized controlled trial (RCT). This study defined outpatient management as patients discharged from the ED or hospitalized for <48 hours. However, only 59 of the 544 patients in the outpatient group were early hospital discharges, while the rest were never admitted. Finally, a specialized thrombosis clinic followed up with the patients within 24 hours of discharge, and patients had telephone access to specialized health care professionals; such organization of care contributed to the safe outpatient management of these PE patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Insurance coverage may present an issue

Medication coverage of direct oral anticoagulants and low molecular weight heparin may present a barrier to patients treated in the outpatient setting who have no insurance or are insured by certain insurance carriers.

ACKNOWLEDGEMENT

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.

Now that we are in the midst of flu season, many discussions regarding the management of patients with influenza virus infections are ensuing. While prevention is always preferable, and we encourage everyone to get vaccinated, influenza remains a rapidly widespread infection. In the United States during last year’s flu season (2017-18), there was an estimated 49 million cases of influenza, 960,000 hospitalizations, and 79,000 deaths. Approximately 86% of all deaths were estimated to occur in those aged 65 and older (Centers for Disease Control and Prevention webpage on Burden of Influenza).

Despite our best efforts, there are inevitable times when some patients become ill enough to require hospitalization. Patients aged 65 and older make up the overwhelming majority of patients with influenza who eventually require hospitalization (Fig 1) (The Centers for Disease Control and Prevention FluView Database). Comorbidities also confer higher risk for more severe illness and potential hospitalization irrespective of age (Fig 2). In children with known medical conditions, asthma confers highest risk of hospitalization, as 27% of those with asthma were hospitalized after developing the flu. In adults, 52% of those with cardiovascular disease and 30% of adult patients with chronic lung disease who were confirmed to have influenza required hospitalization for treatment (Fig 2, The Centers for Disease Control and Prevention FluView Database).

The most severe cases of influenza can require ICU care and advanced management of respiratory failure as a result of the acute respiratory distress syndrome (ARDS). The lungs suffer significant injury due to the viral infection, and they lose their ability to effectively oxygenate the blood. Secondary bacterial infections can also occur as a complication, which compounds the injury. Given the fact that so many patients have significant comorbidities and are of advanced age, it is reasonable to expect that a fair proportion of those with influenza would develop respiratory failure as a consequence. For some of these patients, the hypoxemia that develops as a result of the lung injury can be exceptionally challenging to manage. In extreme cases, conventional ventilator management is insufficient, and the need for additional, advanced therapies arise.

Studies of VV ECMO in severe influenza

ECMO (extracorporeal membrane oxygenation) is a treatment that has been employed to help support patients with severe hypoxemic respiratory failure while their lungs recover from acute injury. Venovenous (VV) ECMO requires peripheral insertion of large cannulae into the venous system to take deoxygenated blood, deliver it through the membrane oxygenator and return the oxygenated blood back to the venous system. In simplest terms, the membrane of ECMO circuit serves as a substitute for the gas exchange function of the lungs and provides the oxygenation that the injured alveoli of the lung are unable to provide. The overall intent is to have the external ECMO circuit do all of the gas exchange work while the lungs heal.

Now that we are in the midst of flu season, many discussions regarding the management of patients with influenza virus infections are ensuing. While prevention is always preferable, and we encourage everyone to get vaccinated, influenza remains a rapidly widespread infection. In the United States during last year’s flu season (2017-18), there was an estimated 49 million cases of influenza, 960,000 hospitalizations, and 79,000 deaths. Approximately 86% of all deaths were estimated to occur in those aged 65 and older (Centers for Disease Control and Prevention webpage on Burden of Influenza).

Despite our best efforts, there are inevitable times when some patients become ill enough to require hospitalization. Patients aged 65 and older make up the overwhelming majority of patients with influenza who eventually require hospitalization (Fig 1) (The Centers for Disease Control and Prevention FluView Database). Comorbidities also confer higher risk for more severe illness and potential hospitalization irrespective of age (Fig 2). In children with known medical conditions, asthma confers highest risk of hospitalization, as 27% of those with asthma were hospitalized after developing the flu. In adults, 52% of those with cardiovascular disease and 30% of adult patients with chronic lung disease who were confirmed to have influenza required hospitalization for treatment (Fig 2, The Centers for Disease Control and Prevention FluView Database).

The most severe cases of influenza can require ICU care and advanced management of respiratory failure as a result of the acute respiratory distress syndrome (ARDS). The lungs suffer significant injury due to the viral infection, and they lose their ability to effectively oxygenate the blood. Secondary bacterial infections can also occur as a complication, which compounds the injury. Given the fact that so many patients have significant comorbidities and are of advanced age, it is reasonable to expect that a fair proportion of those with influenza would develop respiratory failure as a consequence. For some of these patients, the hypoxemia that develops as a result of the lung injury can be exceptionally challenging to manage. In extreme cases, conventional ventilator management is insufficient, and the need for additional, advanced therapies arise.

Studies of VV ECMO in severe influenza

ECMO (extracorporeal membrane oxygenation) is a treatment that has been employed to help support patients with severe hypoxemic respiratory failure while their lungs recover from acute injury. Venovenous (VV) ECMO requires peripheral insertion of large cannulae into the venous system to take deoxygenated blood, deliver it through the membrane oxygenator and return the oxygenated blood back to the venous system. In simplest terms, the membrane of ECMO circuit serves as a substitute for the gas exchange function of the lungs and provides the oxygenation that the injured alveoli of the lung are unable to provide. The overall intent is to have the external ECMO circuit do all of the gas exchange work while the lungs heal.

Now that we are in the midst of flu season, many discussions regarding the management of patients with influenza virus infections are ensuing. While prevention is always preferable, and we encourage everyone to get vaccinated, influenza remains a rapidly widespread infection. In the United States during last year’s flu season (2017-18), there was an estimated 49 million cases of influenza, 960,000 hospitalizations, and 79,000 deaths. Approximately 86% of all deaths were estimated to occur in those aged 65 and older (Centers for Disease Control and Prevention webpage on Burden of Influenza).

Despite our best efforts, there are inevitable times when some patients become ill enough to require hospitalization. Patients aged 65 and older make up the overwhelming majority of patients with influenza who eventually require hospitalization (Fig 1) (The Centers for Disease Control and Prevention FluView Database). Comorbidities also confer higher risk for more severe illness and potential hospitalization irrespective of age (Fig 2). In children with known medical conditions, asthma confers highest risk of hospitalization, as 27% of those with asthma were hospitalized after developing the flu. In adults, 52% of those with cardiovascular disease and 30% of adult patients with chronic lung disease who were confirmed to have influenza required hospitalization for treatment (Fig 2, The Centers for Disease Control and Prevention FluView Database).

The most severe cases of influenza can require ICU care and advanced management of respiratory failure as a result of the acute respiratory distress syndrome (ARDS). The lungs suffer significant injury due to the viral infection, and they lose their ability to effectively oxygenate the blood. Secondary bacterial infections can also occur as a complication, which compounds the injury. Given the fact that so many patients have significant comorbidities and are of advanced age, it is reasonable to expect that a fair proportion of those with influenza would develop respiratory failure as a consequence. For some of these patients, the hypoxemia that develops as a result of the lung injury can be exceptionally challenging to manage. In extreme cases, conventional ventilator management is insufficient, and the need for additional, advanced therapies arise.

Studies of VV ECMO in severe influenza

ECMO (extracorporeal membrane oxygenation) is a treatment that has been employed to help support patients with severe hypoxemic respiratory failure while their lungs recover from acute injury. Venovenous (VV) ECMO requires peripheral insertion of large cannulae into the venous system to take deoxygenated blood, deliver it through the membrane oxygenator and return the oxygenated blood back to the venous system. In simplest terms, the membrane of ECMO circuit serves as a substitute for the gas exchange function of the lungs and provides the oxygenation that the injured alveoli of the lung are unable to provide. The overall intent is to have the external ECMO circuit do all of the gas exchange work while the lungs heal.

Interstitial lung disease (ILD) is becoming more prevalent in patients with RA while shortening survival and leading to substantial health care costs, according to a retrospective study of RA-ILD prevalence, incidence, costs, and mortality.

“To our knowledge, this is the first study to describe the incidence and prevalence of RA-ILD among the general population and to estimate costs among U.S. patients with RA-ILD,” wrote lead author Karina Raimundo, principal health economist at Genentech, and her coauthors in the Journal of Rheumatology.

The study reviewed data from the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases, along with linking a subset of patients to the Social Security Administration Death Index to determine mortality. From 2004 to 2013, with the number of patients ranging from 892 to 3,232 per year, yearly prevalence estimates ranged from 3.2 (95% confidence interval, 3.0-3.4) to 6.0 (95% CI, 5.7-6.2) RA-ILD cases per 100,000 people. Yearly incidence ranged from 2.7 (95% CI, 2.5-2.9) to 3.8 (95% CI, 3.5-4.0) cases per 100,000 people.

While incidence was relatively stable, prevalence increased over the 10-year period. The authors noted that increased prevalence suggests improved survival of RA-ILD patients but were unable to definitively state why, with explanations ranging from more effective therapies to earlier diagnosis of the disease. “Our data do not allow more in-depth evaluation of this issue, and it merits further analysis.”

In addition, they found that average yearly costs across all study years ranged from $40,941 (standard deviation, $55,682) to $51,849 (SD, $77,125), with the main cost drivers being inpatient admissions, outpatient services, and outpatient pharmacy. By the 5-year mark of first diagnosis, 35.9% of RA-ILD patients who could be linked to the SSDI had died; those patients – with a mean age of 65 years – also had a median survival of 7.8 years (95% CI, 7.1-8.3). Generally, a 65-year-old person in the United States would be expected to live for 19 more years.

The authors acknowledged the study’s limitations, including reliance on administrative claims data, subsequent misclassification of RA-ILD status, a lack of information on cause of death, and an underestimation of mortality caused by the inability to link all patients to the Social Security Administration Death Index.

The study was funded by Genentech and F. Hoffmann–La Roche. No other conflicts of interest were reported.

SOURCE: Raimundo K et al. J Rheumatol. 2018 Nov 15. doi: 10.3899/jrheum.171315.

Interstitial lung disease (ILD) is becoming more prevalent in patients with RA while shortening survival and leading to substantial health care costs, according to a retrospective study of RA-ILD prevalence, incidence, costs, and mortality.

“To our knowledge, this is the first study to describe the incidence and prevalence of RA-ILD among the general population and to estimate costs among U.S. patients with RA-ILD,” wrote lead author Karina Raimundo, principal health economist at Genentech, and her coauthors in the Journal of Rheumatology.

The study reviewed data from the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases, along with linking a subset of patients to the Social Security Administration Death Index to determine mortality. From 2004 to 2013, with the number of patients ranging from 892 to 3,232 per year, yearly prevalence estimates ranged from 3.2 (95% confidence interval, 3.0-3.4) to 6.0 (95% CI, 5.7-6.2) RA-ILD cases per 100,000 people. Yearly incidence ranged from 2.7 (95% CI, 2.5-2.9) to 3.8 (95% CI, 3.5-4.0) cases per 100,000 people.

While incidence was relatively stable, prevalence increased over the 10-year period. The authors noted that increased prevalence suggests improved survival of RA-ILD patients but were unable to definitively state why, with explanations ranging from more effective therapies to earlier diagnosis of the disease. “Our data do not allow more in-depth evaluation of this issue, and it merits further analysis.”

In addition, they found that average yearly costs across all study years ranged from $40,941 (standard deviation, $55,682) to $51,849 (SD, $77,125), with the main cost drivers being inpatient admissions, outpatient services, and outpatient pharmacy. By the 5-year mark of first diagnosis, 35.9% of RA-ILD patients who could be linked to the SSDI had died; those patients – with a mean age of 65 years – also had a median survival of 7.8 years (95% CI, 7.1-8.3). Generally, a 65-year-old person in the United States would be expected to live for 19 more years.

The authors acknowledged the study’s limitations, including reliance on administrative claims data, subsequent misclassification of RA-ILD status, a lack of information on cause of death, and an underestimation of mortality caused by the inability to link all patients to the Social Security Administration Death Index.

The study was funded by Genentech and F. Hoffmann–La Roche. No other conflicts of interest were reported.

SOURCE: Raimundo K et al. J Rheumatol. 2018 Nov 15. doi: 10.3899/jrheum.171315.

Interstitial lung disease (ILD) is becoming more prevalent in patients with RA while shortening survival and leading to substantial health care costs, according to a retrospective study of RA-ILD prevalence, incidence, costs, and mortality.

“To our knowledge, this is the first study to describe the incidence and prevalence of RA-ILD among the general population and to estimate costs among U.S. patients with RA-ILD,” wrote lead author Karina Raimundo, principal health economist at Genentech, and her coauthors in the Journal of Rheumatology.

The study reviewed data from the Truven Health MarketScan Commercial and Medicare Supplemental health insurance databases, along with linking a subset of patients to the Social Security Administration Death Index to determine mortality. From 2004 to 2013, with the number of patients ranging from 892 to 3,232 per year, yearly prevalence estimates ranged from 3.2 (95% confidence interval, 3.0-3.4) to 6.0 (95% CI, 5.7-6.2) RA-ILD cases per 100,000 people. Yearly incidence ranged from 2.7 (95% CI, 2.5-2.9) to 3.8 (95% CI, 3.5-4.0) cases per 100,000 people.

While incidence was relatively stable, prevalence increased over the 10-year period. The authors noted that increased prevalence suggests improved survival of RA-ILD patients but were unable to definitively state why, with explanations ranging from more effective therapies to earlier diagnosis of the disease. “Our data do not allow more in-depth evaluation of this issue, and it merits further analysis.”

In addition, they found that average yearly costs across all study years ranged from $40,941 (standard deviation, $55,682) to $51,849 (SD, $77,125), with the main cost drivers being inpatient admissions, outpatient services, and outpatient pharmacy. By the 5-year mark of first diagnosis, 35.9% of RA-ILD patients who could be linked to the SSDI had died; those patients – with a mean age of 65 years – also had a median survival of 7.8 years (95% CI, 7.1-8.3). Generally, a 65-year-old person in the United States would be expected to live for 19 more years.

The authors acknowledged the study’s limitations, including reliance on administrative claims data, subsequent misclassification of RA-ILD status, a lack of information on cause of death, and an underestimation of mortality caused by the inability to link all patients to the Social Security Administration Death Index.

The study was funded by Genentech and F. Hoffmann–La Roche. No other conflicts of interest were reported.

SOURCE: Raimundo K et al. J Rheumatol. 2018 Nov 15. doi: 10.3899/jrheum.171315.

Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.

Cynthia Goldsmith/CDC photo #10073

Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.

In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).

The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.

Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.

Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.

The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.

Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.

Cynthia Goldsmith/CDC photo #10073

Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.

In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).

The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.

Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.

Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.

The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.

Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.

Cynthia Goldsmith/CDC photo #10073

Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.

In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).

The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.

Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.

Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.

The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at pdnews@mdedge.com.

In addition to known risk factors, early reductions in lung function and diffusing capacity increased mortality risk in patients with systemic sclerosis and comorbid interstitial lung disease over 2 years in an analysis of data from the Scleroderma Lung Studies I and II.

First author Elizabeth R. Volkmann, MD, of the University of California, Los Angeles, and her colleagues also reported that although early treatment with cyclophosphamide or mycophenolate mofetil in these studies led to shorter-term improvement in surrogate measures of outcomes for systemic sclerosis and comorbid interstitial lung disease (SSc-ILD), either medication might not improve long-term outcomes. The findings were reported in the Annals of the Rheumatic Diseases.

The investigators identified specific factors linked to an increased risk of death over a median follow-up of 8 years in 158 systemic sclerosis-interstitial lung disease patients in the Scleroderma Lung Study I and median follow-up of 3.6 years in 142 patients in Scleroderma Lung Study II, both of which were randomized, controlled trials.

After follow-up was complete, 42% of participants in Scleroderma Lung Study I and 21% of participants in Scleroderma Lung Study II died, with the most common cause of death being complications related to systemic sclerosis. In addition, no statistical difference was seen in time to death between the intervention arms of both trials.

In building a risk prediction model based on findings from both trials, the investigators confirmed several known mortality risk predictors in systemic sclerosis, including increased age and baseline skin score, but also found that changes in forced vital capacity and diffusing capacity for carbon monoxide over 2 years were separately linked with a greater risk of death.

“These findings suggest that short-term changes in surrogate measures of systemic sclerosis-interstitial lung disease progression may have important effects on long-term outcomes,” the researchers wrote.

The researchers acknowledged the results emphasize the need to determine optimal length of treatment in patients with systemic sclerosis and comorbid interstitial lung disease.

“Systemic sclerosis providers should closely monitor lung function when interstitial lung disease is present to accurately identify declines in lung function and promptly intervene to improve patient outcomes,” the researchers concluded.

The study was funded by the National Institutes of Health and the Scleroderma Foundation. The authors reported no conflicts of interest.

SOURCE: Volkmann ER et al. Ann Rheum Dis. 2018 Nov 8. doi: 10.1136/annrheumdis-2018-213708.

In addition to known risk factors, early reductions in lung function and diffusing capacity increased mortality risk in patients with systemic sclerosis and comorbid interstitial lung disease over 2 years in an analysis of data from the Scleroderma Lung Studies I and II.

First author Elizabeth R. Volkmann, MD, of the University of California, Los Angeles, and her colleagues also reported that although early treatment with cyclophosphamide or mycophenolate mofetil in these studies led to shorter-term improvement in surrogate measures of outcomes for systemic sclerosis and comorbid interstitial lung disease (SSc-ILD), either medication might not improve long-term outcomes. The findings were reported in the Annals of the Rheumatic Diseases.

The investigators identified specific factors linked to an increased risk of death over a median follow-up of 8 years in 158 systemic sclerosis-interstitial lung disease patients in the Scleroderma Lung Study I and median follow-up of 3.6 years in 142 patients in Scleroderma Lung Study II, both of which were randomized, controlled trials.

After follow-up was complete, 42% of participants in Scleroderma Lung Study I and 21% of participants in Scleroderma Lung Study II died, with the most common cause of death being complications related to systemic sclerosis. In addition, no statistical difference was seen in time to death between the intervention arms of both trials.

In building a risk prediction model based on findings from both trials, the investigators confirmed several known mortality risk predictors in systemic sclerosis, including increased age and baseline skin score, but also found that changes in forced vital capacity and diffusing capacity for carbon monoxide over 2 years were separately linked with a greater risk of death.

“These findings suggest that short-term changes in surrogate measures of systemic sclerosis-interstitial lung disease progression may have important effects on long-term outcomes,” the researchers wrote.

The researchers acknowledged the results emphasize the need to determine optimal length of treatment in patients with systemic sclerosis and comorbid interstitial lung disease.

“Systemic sclerosis providers should closely monitor lung function when interstitial lung disease is present to accurately identify declines in lung function and promptly intervene to improve patient outcomes,” the researchers concluded.

The study was funded by the National Institutes of Health and the Scleroderma Foundation. The authors reported no conflicts of interest.

SOURCE: Volkmann ER et al. Ann Rheum Dis. 2018 Nov 8. doi: 10.1136/annrheumdis-2018-213708.

In addition to known risk factors, early reductions in lung function and diffusing capacity increased mortality risk in patients with systemic sclerosis and comorbid interstitial lung disease over 2 years in an analysis of data from the Scleroderma Lung Studies I and II.

First author Elizabeth R. Volkmann, MD, of the University of California, Los Angeles, and her colleagues also reported that although early treatment with cyclophosphamide or mycophenolate mofetil in these studies led to shorter-term improvement in surrogate measures of outcomes for systemic sclerosis and comorbid interstitial lung disease (SSc-ILD), either medication might not improve long-term outcomes. The findings were reported in the Annals of the Rheumatic Diseases.

The investigators identified specific factors linked to an increased risk of death over a median follow-up of 8 years in 158 systemic sclerosis-interstitial lung disease patients in the Scleroderma Lung Study I and median follow-up of 3.6 years in 142 patients in Scleroderma Lung Study II, both of which were randomized, controlled trials.

After follow-up was complete, 42% of participants in Scleroderma Lung Study I and 21% of participants in Scleroderma Lung Study II died, with the most common cause of death being complications related to systemic sclerosis. In addition, no statistical difference was seen in time to death between the intervention arms of both trials.

In building a risk prediction model based on findings from both trials, the investigators confirmed several known mortality risk predictors in systemic sclerosis, including increased age and baseline skin score, but also found that changes in forced vital capacity and diffusing capacity for carbon monoxide over 2 years were separately linked with a greater risk of death.

“These findings suggest that short-term changes in surrogate measures of systemic sclerosis-interstitial lung disease progression may have important effects on long-term outcomes,” the researchers wrote.

The researchers acknowledged the results emphasize the need to determine optimal length of treatment in patients with systemic sclerosis and comorbid interstitial lung disease.

“Systemic sclerosis providers should closely monitor lung function when interstitial lung disease is present to accurately identify declines in lung function and promptly intervene to improve patient outcomes,” the researchers concluded.

The study was funded by the National Institutes of Health and the Scleroderma Foundation. The authors reported no conflicts of interest.

SOURCE: Volkmann ER et al. Ann Rheum Dis. 2018 Nov 8. doi: 10.1136/annrheumdis-2018-213708.