Airway disorders network: Asthma and COPD section

Betting on asthma: The over and under of diagnosis

Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.

Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.

Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).

Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani  et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).

Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.

Richa Nahar, MD 

Network Member-at-Large

Allen J. Blaivas, DO, FCCP 

Network Steering Committee Chair

Diffuse lung disease and lung transplant network: Interstitial lung disease section

Future therapies for IPF

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.

The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.

Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.

Adrian Shifren, MD

Network Member-at-Large

Gabriel Schroeder, MD

Network Member-at-Large

Sleep medicine network: Home-based mechanical ventilation and neuromuscular section

Role of airway clearance therapies in neuromuscular disease

Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).

ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).

Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).

Sherri Katz, MD, FCCP

Section Steering Committee Chair

Critical care network: Mechanical ventilation and airways management section

NIV following extubation: Which devices and which patients?

For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9). 

Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80). 

In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).   

Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9). 

As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation. 

Daniel Ouellette, MD, MS, FCCP

Section Steering Committee Chair
 

Thoracic oncology and chest procedures network: Pleural disease section

Management of recurrent transudative pleural effusions (REDUCE trial)

Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.

In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).

The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.

Maria Azhar, MD

Network Member-at-Large

Saadia A. Faiz, MD FCCP

Section Steering Committee Chair

Airway disorders network: Asthma and COPD section

Betting on asthma: The over and under of diagnosis

Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.

Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.

Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).

Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani  et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).

Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.

Richa Nahar, MD 

Network Member-at-Large

Allen J. Blaivas, DO, FCCP 

Network Steering Committee Chair

Diffuse lung disease and lung transplant network: Interstitial lung disease section

Future therapies for IPF

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.

The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.

Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.

Adrian Shifren, MD

Network Member-at-Large

Gabriel Schroeder, MD

Network Member-at-Large

Sleep medicine network: Home-based mechanical ventilation and neuromuscular section

Role of airway clearance therapies in neuromuscular disease

Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).

ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).

Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).

Sherri Katz, MD, FCCP

Section Steering Committee Chair

Critical care network: Mechanical ventilation and airways management section

NIV following extubation: Which devices and which patients?

For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9). 

Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80). 

In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).   

Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9). 

As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation. 

Daniel Ouellette, MD, MS, FCCP

Section Steering Committee Chair
 

Thoracic oncology and chest procedures network: Pleural disease section

Management of recurrent transudative pleural effusions (REDUCE trial)

Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.

In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).

The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.

Maria Azhar, MD

Network Member-at-Large

Saadia A. Faiz, MD FCCP

Section Steering Committee Chair

Airway disorders network: Asthma and COPD section

Betting on asthma: The over and under of diagnosis

Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.

Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.

Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).

Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani  et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).

Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.

Richa Nahar, MD 

Network Member-at-Large

Allen J. Blaivas, DO, FCCP 

Network Steering Committee Chair

Diffuse lung disease and lung transplant network: Interstitial lung disease section

Future therapies for IPF

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.

The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.

Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.

Adrian Shifren, MD

Network Member-at-Large

Gabriel Schroeder, MD

Network Member-at-Large

Sleep medicine network: Home-based mechanical ventilation and neuromuscular section

Role of airway clearance therapies in neuromuscular disease

Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).

ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).

Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).

Sherri Katz, MD, FCCP

Section Steering Committee Chair

Critical care network: Mechanical ventilation and airways management section

NIV following extubation: Which devices and which patients?

For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9). 

Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80). 

In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).   

Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9). 

As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation. 

Daniel Ouellette, MD, MS, FCCP

Section Steering Committee Chair
 

Thoracic oncology and chest procedures network: Pleural disease section

Management of recurrent transudative pleural effusions (REDUCE trial)

Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.

In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).

The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.

Maria Azhar, MD

Network Member-at-Large

Saadia A. Faiz, MD FCCP

Section Steering Committee Chair

Barriers and Enablers to Objective Testing for Asthma and COPD in Primary Care: A Systematic Review Using the Theoretical Domains Framework
By Dr. Janet Yamada et al.

COVID Complications: Diagnostic and Therapeutic Considerations for Critical Covid
By Dr. David M. Maslove et al.

Interstitial Lung Abnormalities, Emphysema, and Spirometry in Smokers
By Dr. Aravind A. Menon et al.

Sleep-Disordered Breathing in Hospitalized Patients: A Game Changer?
By Dr. Sunil Sharma and Dr. Robert Stansbury.

Distribution, Risk Factors, and Temporal Trends for Lung Cancer Incidence and Mortality: A Global Analysis 
By Dr. Junjie Huang et al.

Barriers and Enablers to Objective Testing for Asthma and COPD in Primary Care: A Systematic Review Using the Theoretical Domains Framework
By Dr. Janet Yamada et al.

COVID Complications: Diagnostic and Therapeutic Considerations for Critical Covid
By Dr. David M. Maslove et al.

Interstitial Lung Abnormalities, Emphysema, and Spirometry in Smokers
By Dr. Aravind A. Menon et al.

Sleep-Disordered Breathing in Hospitalized Patients: A Game Changer?
By Dr. Sunil Sharma and Dr. Robert Stansbury.

Distribution, Risk Factors, and Temporal Trends for Lung Cancer Incidence and Mortality: A Global Analysis 
By Dr. Junjie Huang et al.

Barriers and Enablers to Objective Testing for Asthma and COPD in Primary Care: A Systematic Review Using the Theoretical Domains Framework
By Dr. Janet Yamada et al.

COVID Complications: Diagnostic and Therapeutic Considerations for Critical Covid
By Dr. David M. Maslove et al.

Interstitial Lung Abnormalities, Emphysema, and Spirometry in Smokers
By Dr. Aravind A. Menon et al.

Sleep-Disordered Breathing in Hospitalized Patients: A Game Changer?
By Dr. Sunil Sharma and Dr. Robert Stansbury.

Distribution, Risk Factors, and Temporal Trends for Lung Cancer Incidence and Mortality: A Global Analysis 
By Dr. Junjie Huang et al.

Despite current guidelines permitting opt-out STI screening and the ability in most states to treat adolescents 13 years old and older for STIs without parental notification, STI testing rates remain low. The articles about the 2019 survey raise several concerns.

Screening was more common with certain known risky behaviors, so risk-based screening seems prevalent. Of note, one recently reported factor increasing risky behaviors, but not noted above, is homelessness, suggesting it also be a trigger for STI screening (Child Youth Services Rev. 2022;139. doi: 10.1016/j.childyouth.2022.106538). But won’t risk-based screening inevitably lead to undertesting/treating? Are adolescents comfortable/willing to answer even the most carefully crafted, gentle, and simple questions about risky behaviors? 

Because STIs are so frequent in adolescents (many asymptomatic), is risk-based screening/testing adequate for common STIs? Could urine-based screening for gonorrhea and chlamydia be useful in any adolescent who has been sexually active or uses the ED for routine care? Syphilis seems different. Screening requires a blood draw and is more difficult to implement, so risk-based testing seems okay. Also, the CDC recommends risk-based screening for syphilis.

Chief complaints at adolescent visits are usually not STI-related, unless symptomatic or visible, e.g., genital warts or herpes. So STI screening (even opt-out) will lengthen visits, perhaps a lot, over what was scheduled – even if only to explain negative results. Multiple visits with screening in the same morning could wreck patient flow. Maybe this doesn’t influence decisions to screen/test, but reexamining our approach can maximize appropriate STI screening/testing. 

STIs run in packs, so if you detect one, expand testing to include the others. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.
 

Despite current guidelines permitting opt-out STI screening and the ability in most states to treat adolescents 13 years old and older for STIs without parental notification, STI testing rates remain low. The articles about the 2019 survey raise several concerns.

Screening was more common with certain known risky behaviors, so risk-based screening seems prevalent. Of note, one recently reported factor increasing risky behaviors, but not noted above, is homelessness, suggesting it also be a trigger for STI screening (Child Youth Services Rev. 2022;139. doi: 10.1016/j.childyouth.2022.106538). But won’t risk-based screening inevitably lead to undertesting/treating? Are adolescents comfortable/willing to answer even the most carefully crafted, gentle, and simple questions about risky behaviors? 

Because STIs are so frequent in adolescents (many asymptomatic), is risk-based screening/testing adequate for common STIs? Could urine-based screening for gonorrhea and chlamydia be useful in any adolescent who has been sexually active or uses the ED for routine care? Syphilis seems different. Screening requires a blood draw and is more difficult to implement, so risk-based testing seems okay. Also, the CDC recommends risk-based screening for syphilis.

Chief complaints at adolescent visits are usually not STI-related, unless symptomatic or visible, e.g., genital warts or herpes. So STI screening (even opt-out) will lengthen visits, perhaps a lot, over what was scheduled – even if only to explain negative results. Multiple visits with screening in the same morning could wreck patient flow. Maybe this doesn’t influence decisions to screen/test, but reexamining our approach can maximize appropriate STI screening/testing. 

STIs run in packs, so if you detect one, expand testing to include the others. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.
 

Despite current guidelines permitting opt-out STI screening and the ability in most states to treat adolescents 13 years old and older for STIs without parental notification, STI testing rates remain low. The articles about the 2019 survey raise several concerns.

Screening was more common with certain known risky behaviors, so risk-based screening seems prevalent. Of note, one recently reported factor increasing risky behaviors, but not noted above, is homelessness, suggesting it also be a trigger for STI screening (Child Youth Services Rev. 2022;139. doi: 10.1016/j.childyouth.2022.106538). But won’t risk-based screening inevitably lead to undertesting/treating? Are adolescents comfortable/willing to answer even the most carefully crafted, gentle, and simple questions about risky behaviors? 

Because STIs are so frequent in adolescents (many asymptomatic), is risk-based screening/testing adequate for common STIs? Could urine-based screening for gonorrhea and chlamydia be useful in any adolescent who has been sexually active or uses the ED for routine care? Syphilis seems different. Screening requires a blood draw and is more difficult to implement, so risk-based testing seems okay. Also, the CDC recommends risk-based screening for syphilis.

Chief complaints at adolescent visits are usually not STI-related, unless symptomatic or visible, e.g., genital warts or herpes. So STI screening (even opt-out) will lengthen visits, perhaps a lot, over what was scheduled – even if only to explain negative results. Multiple visits with screening in the same morning could wreck patient flow. Maybe this doesn’t influence decisions to screen/test, but reexamining our approach can maximize appropriate STI screening/testing. 

STIs run in packs, so if you detect one, expand testing to include the others. 

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.
 

SEATTLE – An update from a phase 2 study – core and open-label extension – of lecanemab in Alzheimer’s disease showed that the antibody reduced amyloid plaques within the first months after treatment initiation, and this effect was associated with improved clinical signs in as early as 6 months. The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.

Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
 

Are amyloid plaques a key driver of Alzheimer’s disease?

The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.

Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
 

Searching for the best dose and dose frequency

Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.

The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.

The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.

The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.

At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).

There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.

Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.

Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.

SEATTLE – An update from a phase 2 study – core and open-label extension – of lecanemab in Alzheimer’s disease showed that the antibody reduced amyloid plaques within the first months after treatment initiation, and this effect was associated with improved clinical signs in as early as 6 months. The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.

Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
 

Are amyloid plaques a key driver of Alzheimer’s disease?

The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.

Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
 

Searching for the best dose and dose frequency

Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.

The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.

The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.

The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.

At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).

There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.

Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.

Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.

SEATTLE – An update from a phase 2 study – core and open-label extension – of lecanemab in Alzheimer’s disease showed that the antibody reduced amyloid plaques within the first months after treatment initiation, and this effect was associated with improved clinical signs in as early as 6 months. The researchers identified two plasma biomarkers that correlate well with established amyloid PET standard uptake value ratio (SUVr) changes, potentially paving the way for monitoring lecanemab treatment effects. The researchers also found evidence that the plasma biomarker could be used to allow dose frequency reduction after initial reduction in amyloid plaques.

Lecanemab preferably targets aggregated species of amyloid called protofibrils, which is unique among anti-amyloid antibodies, and these are also among the most toxic manifestations of amyloid, according to Chad Swanson, PhD, who presented the study at the 2022 annual meeting of the American Academy of Neurology.
 

Are amyloid plaques a key driver of Alzheimer’s disease?

The study could help answer the question of whether amyloid plaques drive the cognitive decline seen in Alzheimer’s disease, in part because the antibody is so effective at what it was designed to do, according to Fernando Testai, MD, PhD, who comoderated the session where the study was presented. “The effect on amyloid content that they measured was persistent over a number of months. Cognition may follow along, so more studies have to be done, but the medication seems to be quite effective doing what it’s supposed to do. If it has something to do with disease, these treatments actually should give us the answer, because the effect on amyloid is pretty significant. After so many years of thinking amyloid probably has nothing to do (with Alzheimer’s symptoms, these results suggest) it may have something to do with the disease,” Dr. Testai said in an interview. He is a professor of neurology at the University of Illinois at Chicago.

Dr. Swanson is confident that amyloid plaques are a key driver of disease. “I’d say a number of companies now with anti-amyloid agents have shown that targeting amyloid can produce some slowing of clinical decline, as well as a robust reduction in amyloid, supporting this idea that that amyloid is meaningful. And it’s very clear that amyloid [deposition] tends to trigger tau pathology,” said Dr. Swanson in an interview. He is executive director of the neurology business group at Eisai Pharmaceuticals, which is developing the anti-amyloid antibody, called lecanemab.
 

Searching for the best dose and dose frequency

Dr. Swanson noted that Eisai has already conducted a large phase 2b study which informed the current phase 3 ClarityAD study design. The phase 2b study utilized a Bayesian adaptive design, which allocated more patients in a fully blinded way to doses that had the most potential for slowing clinical decline. “The intent was to maximize the efficiency of the design so that more subjects would go to a dose that looks like it could be the best dose according to the Bayesian algorithm,” said Dr. Swanson.

The study also included a gap period that followed the randomized phase of the trial, where subjects were not being dosed with the antibody from 9 to 59 months (mean, 2 years), before reinitiation at the start of the open-label extension phase. “[That] allowed us to answer some really important questions about what happens when you remove lecanemab after reducing amyloid, and then what happens when you reintroduce lecanemab in the open-label extension,” said Dr. Swanson.

The researchers found that amyloid reaccumulated during the treatment gap, and soluble biomarkers were potentially the most sensitive to the change. “Taking all of this information together with clinical data that suggest potential disease-modifying effects, it suggests that we need to continue to treat these individuals, but we may be able to treat with a less-frequent dosing interval once amyloid is removed from the brain. It’s a biweekly infusion. Following 18 months of treatment, we may be able to go in once every month or once every 3 months to maintain low levels of amyloid. We’re going to be testing that soon in the current phase 2 open-label extension,” said Dr. Swanson.

The study included 856 patients who were randomized to biweekly placebo or lecanemab 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, or 10 mg/kg biweekly. The primary endpoint was the Alzheimer’s disease composite score at 12 months; secondary endpoints included ADCOMS and various biomarker levels at 18 months.

At 18 months, the 10-mg/kg biweekly group had an adjusted mean change from placebo in brain amyloid of –0.31 SUVr units, with more than 80% of the subjects converting from amyloid positive to amyloid negative by visual read. Most subjects remained amyloid negative at open-label extension baseline following the gap period despite a slow reaccumulation of amyloid plaque in the treated group. Out to 18 months in the core study, the same group had a 30% reduction in cognitive decline, compared with placebo, as measured by ADCOMS (P < .05).

There was a correlation between PET SUVr, clinical outcomes, and the Abeta42/40 ratio and plasma p-tau181. During the gap period, treatment discontinuation was associated with changes in the plasma biomarkers that echoed amyloid re-accumulation and clinical decline. Change from baseline in both plasma biomarkers were associated with a change from baseline in PET SUVr at 18 months.

Amyloid-related imaging abnormalities related to brain edema or sulcal effusion (ARIA-E) occurred in 9.9% of patients during the randomized phase of the trial, and 7.8% during the open-label extension phase. About 2% were symptomatic in both the randomization and open-label extension phases. The majority of ARIA-E cases appeared within 3 months of treatment initiation, and generally resolved in 4-16 weeks. 80% were mild to moderate by radiography.

Dr. Swanson is an employee of Eisai Pharmaceuticals, which sponsored the study. Dr. Testai has no relevant financial disclosures.

AGA Fellow (AGAF) applications now open

Applications are now open for the 2023 AGA Fellowship cohort. AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.

Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:

• The privilege of using the designation “AGAF” in professional activities. 
• An official certificate and pin denoting your status. 
• International acknowledgment at Digestive Disease Week® (DDW).
• A listing on the AGA website alongside esteemed peers.  
• A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.

Learn more

Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.

If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.

AGA Fellow (AGAF) applications now open

Applications are now open for the 2023 AGA Fellowship cohort. AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.

Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:

• The privilege of using the designation “AGAF” in professional activities. 
• An official certificate and pin denoting your status. 
• International acknowledgment at Digestive Disease Week® (DDW).
• A listing on the AGA website alongside esteemed peers.  
• A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.

Learn more

Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.

If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.

AGA Fellow (AGAF) applications now open

Applications are now open for the 2023 AGA Fellowship cohort. AGA is proud to formally recognize its exemplary members whose accomplishments and contributions demonstrate a deep commitment to gastroenterology through the AGA Fellows Program. Those in clinical practice, education, or research (basic or clinical) are encouraged to apply today.

Longstanding members who apply and meet the program criteria are granted the distinguished honor of AGA Fellowship and receive the following:

• The privilege of using the designation “AGAF” in professional activities. 
• An official certificate and pin denoting your status. 
• International acknowledgment at Digestive Disease Week® (DDW).
• A listing on the AGA website alongside esteemed peers.  
• A prewritten, fill-in press release, and a digital badge to inform others of your accomplishment.

Learn more

Apply for consideration and gain recognition worldwide for your commitment to the field. The deadline is Aug. 24, 2022.

If you have any questions, contact AGA Member Relations at member@gastro.org or 301-941-2651.

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

Early meniscal surgery does not appear to be better than a program of exercise and education in improving knee outcomes in young adults with meniscal tears, according to the results of the randomized controlled DREAM trial presented at the OARSI 2022 World Congress.

Indeed, similar clinically relevant improvements in knee pain, function, and quality of life at 12 months were seen among participants in both study arms.

“Our results highlight that decisions on surgery or nonsurgical treatment must depend on preferences and values and needs of the individuals consulting their surgeon,” Søren T. Skou, PT, MSc, PhD, reported during one of the opening sessions at the meeting sponsored by the Osteoarthritis Research Society International.

The lack of superiority was contrary to the expectations of the researchers who hypothesized that early surgical intervention in adults aged between 18 and 40 years would be more beneficial than an active rehabilitation program with later surgery if needed.

Although the results do tie in with the results of other trials and systematic reviews in older adults the reason for looking at young adults specifically, aside from the obvious differences and the origin of meniscal tears, was that no study had previously looked at this population, Dr. Skou explained.
 

Assembling the DREAM team

The DREAM (Danish RCT on Exercise versus Arthroscopic Meniscal Surgery for Young Adults) trial “was a collaborative effort among many clinicians in Denmark – physical therapists, exercise physiologists, and surgeons,” Dr. Skou observed.

In total, 121 adults with MRI-verified meniscal tears who were eligible for surgery were recruited and randomized to either the early meniscal surgery group (n = 60) or to the exercise and education group (n = 61). The mean age was just below 30 years and 28% were female

Meniscal surgery, which was either an arthroscopic partial meniscectomy or meniscal repair, was performed at seven specialist centers. The exercise and education program was delivered by trained physical therapists working at 19 participating centers. The latter consisted of 24 sessions of group-based exercise therapy and education held over a period of 12 weeks.

Participants randomized to the exercise and education arm had the option of later meniscal surgery, with one in four eventually undergoing this procedure.
 

No gain in pain

The primary outcome measure was the difference in the mean of four of the subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) from baseline to 12-month assessment. The KOOS4 looks at knee pain, symptoms, function in sport and recreation, and quality of life.

“We considered a 10-point difference between groups as clinically relevant,” said Dr. Skou, but “adjusting for the baseline differences, we found no [statistical] differences or clinically relevant differences between groups.”

Improvement was seen in both groups. In an intention-to-treat analysis the KOOS4 scores improved by 19.2 points and 16.4 points respectively in the surgery and exercise and education groups, with a mean adjusted difference of 5.4 (95% confidence interval, –0.7 to 11.4). There was also no difference in a per protocol analysis, which considered only those participants who received the treatment strategy they were allocated (mean adjusted difference, 5.7; 95% CI, –0.9 to 12.4).

Secondary outcomes were also similarly improved in both groups with clinically relevant increases in all four KOOS subscale scores and in the Western Ontario Meniscal Evaluation Tool (WOMET).

While there were some statistical differences between the groups, such as better KOOS pain, symptoms, and WOMET scores in the surgery group, these were felt unlikely to be clinically relevant. Likewise, there was a statistically greater improvement in muscle strength in the exercise and education group than surgery group.

There was no statistical difference in the number of serious adverse events, including worsening of symptoms with or without acute onset during activity and lateral meniscal cysts, with four reported in the surgical group and seven in the exercise and education group.
 

Views on results

The results of the trial, published in NEJM Evidence, garnered attention on Twitter with several physiotherapists noting the data were positive for the nonsurgical management of meniscal tears in younger adults.

During discussion at the meeting, Nadine Foster, PhD, NIHR Professor of Musculoskeletal Health in Primary Care at Keele (England) University, asked if a larger cohort might not swing the results in favor of surgery.

She said: “Congratulations on this trial. The challenge: Your 95% CIs suggest a larger trial would have concluded superiority of surgery?”

Dr. Skou responded: “Most likely the true difference is outside the clinically relevant difference, but obviously, we cannot exclude that there is actually a clinically relevant difference between groups.”

Martin Englund, MD, Phd, of Lund (Sweden) University Hospital in Sweden, pointed out that 16 patients in the exercise and education group had “crossed over” and undergone surgery. “Were there any differences for those patients?” he asked.

“We looked at whether there was a difference between those – obviously only having 16 participants, we’re not able to do any statistical comparisons – but looking just visually at the data, they seem to improve to the same extent as those undergoing nonsurgical only,” Dr. Skou said.

The 2-year MRI data are currently being examined and will “obviously also be very interesting,” he added.

The DREAM trial was funded by the Danish Council for Independent Research, IMK Almene Fond, Lundbeck Foundation, Spar Nord Foundation, Danish Rheumatism Association, Association of Danish Physiotherapists Research Fund, Research Council at Næstved-Slagelse-Ringsted Hospitals, and Region Zealand. Dr. Skou had no financial or other conflicts of interest to disclose.

The American Academy of Pediatrics, with funding from the Centers for Disease Control and Prevention, studied the CDC’s “Learn the Signs. Act Early” developmental surveillance milestones for children 0-5 years to update the milestones based on published studies. The goal was to improve this tool for developmental surveillance and use by the public. Developmental surveillance is not just observing a child at a check-up but rather “is a longitudinal process that involves eliciting concerns, taking a developmental history based on milestone attainment, observing milestones and other behaviors, examining the child, and applying clinical judgment during health supervision visits (HSVs).”¹

While the milestones we were trained on were a good start and highlighted the developmental progression central to pediatrics, they were not based on norms or cut scores indicating significant developmental risk unless taught from a validated tool. The CDC was concerned that their public handouts and apps were based on median ages (middle number of the entire range) of attainment not the mode (most common) or even average ages. That means that about half of all typically developing children would “not have attained” that skill at the age noted, potentially evoking unnecessary concern for parents and a “wait-and-see” message from a knowledgeable provider who realized the statistical meaning and the broad range of normal. Another potential problem with using milestones set at the median age is that parents, especially those with several children or experienced friends, may see the provider as an alarmist when they have seen great variation in children who later were normal. This reaction can dampen provider willingness to discuss development or even to screen with validated tools. We have learned the hard way from COVID-19 that it is difficult to convey concepts of risk effectively both balancing fear and stimulating action.

The AAP experts reviewed the English literature for data-based milestones, finding 34 articles, 10 of which had an opinion for at least one milestone. If this sounds like a very small number, you are correct. You may not realize that almost all screening and diagnostic tools have been based on data collected by Gesell in 1928!² While most of health care has changed since then, which milestones are measured in infants has not.

The biggest change from this review was deciding to use as milestones skills reported for 75% of children at each age of typical HSVs, adding ones for 15 and 30 months. The implication is that children not attaining these milestones are all at risk and deserving of more careful history, examination, and administration of a validated screening tool; not true when based on median data. Of the 94 existing CDC milestones retained after the review, one-third were moved to a different age with 21 of 31 assigned to an older age. Domains of functioning for the milestones were consolidated into social emotional, cognitive, language/communication, and motor, to help parents learn to distinguish these areas, and, although many milestones reflect several domains, each was included only once to reduce confusion.

Psychosocial assessment is recommended by the AAP and Bright Futures at every HSV but the fewest milestones with normative data were identified for this domain, often self-help rather than social engagement or emotion regulation skills. The cross-cultural study cited for many of the new milestones was reassuring overall in that the median ages for 67%-88% of milestones in most domains were equivalent across the four countries sampled, but only 22% of self-help skills were equivalent.³ This should remind us that parenting has more influence over psychosocial skills than other domains. Psychosocial and behavioral functioning, especially emotional regulation, also deserve “surveillance” as they have enormous impact on life outcomes but need to be measured and supported differently. Routine use of validated tools such as the Early Childhood Screening Assessment or the Ages & Stages Questionnaires: Social-Emotional for these domains are also needed.

Normal variations in temperament and patterns of attachment can affect many milestones including courage for walking, exploration, social engagement, and prosocial behaviors or self-control for social situations, attention, range of affect, and cooperation. All of these skills are among the 42 total (14 new) social-emotional milestones for 0- to 5-year-olds. Variations in these functions are at the root of the most common “challenging behaviors” in our studies in primary care. They are also the most vulnerable to suboptimal parent-child relationships, adverse childhood experiences, and social determinants of health.

As primary care providers, we not only need to detect children at risk for developmental problems but also promote and celebrate developmental progress. I hope that changing the threshold for concern to 75% will allow for a more positive review with the family (as fewer will be flagged as at risk) and chance to congratulate parents on all that is going well. But I also hope the change will not make us overlook parenting challenges, often from the psychosocial milestones most amenable to our guidance and support.

Early identification is mainly important to obtain the early intervention shown to improve outcomes. However, less than 25% of children with delays or disabilities receive early intervention before age 3 and most with emotional, behavioral, and developmental conditions, other than autism spectrum disorder, not before age 5. Since early intervention services are freely available in all states, we also need to do better at getting children to this care.

Let’s reconsider the process of developmental surveillance in this light of delayed referral: “Eliciting concerns” is key as parents have been shown to be usually correct in their worries. Listening to how they express the concerns can help you connect their specific issues when discussing reasons for referral. While most parent “recall of past milestones” is not accurate, current milestones reported are; thus, the need to have the new more accurate norms for all ages for comparison. When we make observations of a child’s abilities and behaviors ourselves we may not only pick up on issues missed by the parent, but will be more convincing in conveying the need for referral when indicated. When we “examine” the child we can use our professional skills to determine the very important risk factor of the quality of how a skill is performed, not just that it is. The recommended “use of validated screening tools” when the new milestones are not met give us an objective tool to share with parents, more confidence in when referral is warranted, which we will convey to parents (and perhaps skeptical relatives), and baseline documentation from which we can “track” referrals, progress, and, hopefully, better outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Zubler JM et al. Pediatrics. 2022;149(3):e2021052138.

2. Gessell A et al. Macmillan: New York, 1928.

3. Ertem IO et al. Lancet Glob Health. 2018 Mar;6(3):e279-91.

The American Academy of Pediatrics, with funding from the Centers for Disease Control and Prevention, studied the CDC’s “Learn the Signs. Act Early” developmental surveillance milestones for children 0-5 years to update the milestones based on published studies. The goal was to improve this tool for developmental surveillance and use by the public. Developmental surveillance is not just observing a child at a check-up but rather “is a longitudinal process that involves eliciting concerns, taking a developmental history based on milestone attainment, observing milestones and other behaviors, examining the child, and applying clinical judgment during health supervision visits (HSVs).”¹

While the milestones we were trained on were a good start and highlighted the developmental progression central to pediatrics, they were not based on norms or cut scores indicating significant developmental risk unless taught from a validated tool. The CDC was concerned that their public handouts and apps were based on median ages (middle number of the entire range) of attainment not the mode (most common) or even average ages. That means that about half of all typically developing children would “not have attained” that skill at the age noted, potentially evoking unnecessary concern for parents and a “wait-and-see” message from a knowledgeable provider who realized the statistical meaning and the broad range of normal. Another potential problem with using milestones set at the median age is that parents, especially those with several children or experienced friends, may see the provider as an alarmist when they have seen great variation in children who later were normal. This reaction can dampen provider willingness to discuss development or even to screen with validated tools. We have learned the hard way from COVID-19 that it is difficult to convey concepts of risk effectively both balancing fear and stimulating action.

The AAP experts reviewed the English literature for data-based milestones, finding 34 articles, 10 of which had an opinion for at least one milestone. If this sounds like a very small number, you are correct. You may not realize that almost all screening and diagnostic tools have been based on data collected by Gesell in 1928!² While most of health care has changed since then, which milestones are measured in infants has not.

The biggest change from this review was deciding to use as milestones skills reported for 75% of children at each age of typical HSVs, adding ones for 15 and 30 months. The implication is that children not attaining these milestones are all at risk and deserving of more careful history, examination, and administration of a validated screening tool; not true when based on median data. Of the 94 existing CDC milestones retained after the review, one-third were moved to a different age with 21 of 31 assigned to an older age. Domains of functioning for the milestones were consolidated into social emotional, cognitive, language/communication, and motor, to help parents learn to distinguish these areas, and, although many milestones reflect several domains, each was included only once to reduce confusion.

Psychosocial assessment is recommended by the AAP and Bright Futures at every HSV but the fewest milestones with normative data were identified for this domain, often self-help rather than social engagement or emotion regulation skills. The cross-cultural study cited for many of the new milestones was reassuring overall in that the median ages for 67%-88% of milestones in most domains were equivalent across the four countries sampled, but only 22% of self-help skills were equivalent.³ This should remind us that parenting has more influence over psychosocial skills than other domains. Psychosocial and behavioral functioning, especially emotional regulation, also deserve “surveillance” as they have enormous impact on life outcomes but need to be measured and supported differently. Routine use of validated tools such as the Early Childhood Screening Assessment or the Ages & Stages Questionnaires: Social-Emotional for these domains are also needed.

Normal variations in temperament and patterns of attachment can affect many milestones including courage for walking, exploration, social engagement, and prosocial behaviors or self-control for social situations, attention, range of affect, and cooperation. All of these skills are among the 42 total (14 new) social-emotional milestones for 0- to 5-year-olds. Variations in these functions are at the root of the most common “challenging behaviors” in our studies in primary care. They are also the most vulnerable to suboptimal parent-child relationships, adverse childhood experiences, and social determinants of health.

As primary care providers, we not only need to detect children at risk for developmental problems but also promote and celebrate developmental progress. I hope that changing the threshold for concern to 75% will allow for a more positive review with the family (as fewer will be flagged as at risk) and chance to congratulate parents on all that is going well. But I also hope the change will not make us overlook parenting challenges, often from the psychosocial milestones most amenable to our guidance and support.

Early identification is mainly important to obtain the early intervention shown to improve outcomes. However, less than 25% of children with delays or disabilities receive early intervention before age 3 and most with emotional, behavioral, and developmental conditions, other than autism spectrum disorder, not before age 5. Since early intervention services are freely available in all states, we also need to do better at getting children to this care.

Let’s reconsider the process of developmental surveillance in this light of delayed referral: “Eliciting concerns” is key as parents have been shown to be usually correct in their worries. Listening to how they express the concerns can help you connect their specific issues when discussing reasons for referral. While most parent “recall of past milestones” is not accurate, current milestones reported are; thus, the need to have the new more accurate norms for all ages for comparison. When we make observations of a child’s abilities and behaviors ourselves we may not only pick up on issues missed by the parent, but will be more convincing in conveying the need for referral when indicated. When we “examine” the child we can use our professional skills to determine the very important risk factor of the quality of how a skill is performed, not just that it is. The recommended “use of validated screening tools” when the new milestones are not met give us an objective tool to share with parents, more confidence in when referral is warranted, which we will convey to parents (and perhaps skeptical relatives), and baseline documentation from which we can “track” referrals, progress, and, hopefully, better outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Zubler JM et al. Pediatrics. 2022;149(3):e2021052138.

2. Gessell A et al. Macmillan: New York, 1928.

3. Ertem IO et al. Lancet Glob Health. 2018 Mar;6(3):e279-91.

The American Academy of Pediatrics, with funding from the Centers for Disease Control and Prevention, studied the CDC’s “Learn the Signs. Act Early” developmental surveillance milestones for children 0-5 years to update the milestones based on published studies. The goal was to improve this tool for developmental surveillance and use by the public. Developmental surveillance is not just observing a child at a check-up but rather “is a longitudinal process that involves eliciting concerns, taking a developmental history based on milestone attainment, observing milestones and other behaviors, examining the child, and applying clinical judgment during health supervision visits (HSVs).”¹

While the milestones we were trained on were a good start and highlighted the developmental progression central to pediatrics, they were not based on norms or cut scores indicating significant developmental risk unless taught from a validated tool. The CDC was concerned that their public handouts and apps were based on median ages (middle number of the entire range) of attainment not the mode (most common) or even average ages. That means that about half of all typically developing children would “not have attained” that skill at the age noted, potentially evoking unnecessary concern for parents and a “wait-and-see” message from a knowledgeable provider who realized the statistical meaning and the broad range of normal. Another potential problem with using milestones set at the median age is that parents, especially those with several children or experienced friends, may see the provider as an alarmist when they have seen great variation in children who later were normal. This reaction can dampen provider willingness to discuss development or even to screen with validated tools. We have learned the hard way from COVID-19 that it is difficult to convey concepts of risk effectively both balancing fear and stimulating action.

The AAP experts reviewed the English literature for data-based milestones, finding 34 articles, 10 of which had an opinion for at least one milestone. If this sounds like a very small number, you are correct. You may not realize that almost all screening and diagnostic tools have been based on data collected by Gesell in 1928!² While most of health care has changed since then, which milestones are measured in infants has not.

The biggest change from this review was deciding to use as milestones skills reported for 75% of children at each age of typical HSVs, adding ones for 15 and 30 months. The implication is that children not attaining these milestones are all at risk and deserving of more careful history, examination, and administration of a validated screening tool; not true when based on median data. Of the 94 existing CDC milestones retained after the review, one-third were moved to a different age with 21 of 31 assigned to an older age. Domains of functioning for the milestones were consolidated into social emotional, cognitive, language/communication, and motor, to help parents learn to distinguish these areas, and, although many milestones reflect several domains, each was included only once to reduce confusion.

Psychosocial assessment is recommended by the AAP and Bright Futures at every HSV but the fewest milestones with normative data were identified for this domain, often self-help rather than social engagement or emotion regulation skills. The cross-cultural study cited for many of the new milestones was reassuring overall in that the median ages for 67%-88% of milestones in most domains were equivalent across the four countries sampled, but only 22% of self-help skills were equivalent.³ This should remind us that parenting has more influence over psychosocial skills than other domains. Psychosocial and behavioral functioning, especially emotional regulation, also deserve “surveillance” as they have enormous impact on life outcomes but need to be measured and supported differently. Routine use of validated tools such as the Early Childhood Screening Assessment or the Ages & Stages Questionnaires: Social-Emotional for these domains are also needed.

Normal variations in temperament and patterns of attachment can affect many milestones including courage for walking, exploration, social engagement, and prosocial behaviors or self-control for social situations, attention, range of affect, and cooperation. All of these skills are among the 42 total (14 new) social-emotional milestones for 0- to 5-year-olds. Variations in these functions are at the root of the most common “challenging behaviors” in our studies in primary care. They are also the most vulnerable to suboptimal parent-child relationships, adverse childhood experiences, and social determinants of health.

As primary care providers, we not only need to detect children at risk for developmental problems but also promote and celebrate developmental progress. I hope that changing the threshold for concern to 75% will allow for a more positive review with the family (as fewer will be flagged as at risk) and chance to congratulate parents on all that is going well. But I also hope the change will not make us overlook parenting challenges, often from the psychosocial milestones most amenable to our guidance and support.

Early identification is mainly important to obtain the early intervention shown to improve outcomes. However, less than 25% of children with delays or disabilities receive early intervention before age 3 and most with emotional, behavioral, and developmental conditions, other than autism spectrum disorder, not before age 5. Since early intervention services are freely available in all states, we also need to do better at getting children to this care.

Let’s reconsider the process of developmental surveillance in this light of delayed referral: “Eliciting concerns” is key as parents have been shown to be usually correct in their worries. Listening to how they express the concerns can help you connect their specific issues when discussing reasons for referral. While most parent “recall of past milestones” is not accurate, current milestones reported are; thus, the need to have the new more accurate norms for all ages for comparison. When we make observations of a child’s abilities and behaviors ourselves we may not only pick up on issues missed by the parent, but will be more convincing in conveying the need for referral when indicated. When we “examine” the child we can use our professional skills to determine the very important risk factor of the quality of how a skill is performed, not just that it is. The recommended “use of validated screening tools” when the new milestones are not met give us an objective tool to share with parents, more confidence in when referral is warranted, which we will convey to parents (and perhaps skeptical relatives), and baseline documentation from which we can “track” referrals, progress, and, hopefully, better outcomes.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at pdnews@mdedge.com.

References

1. Zubler JM et al. Pediatrics. 2022;149(3):e2021052138.

2. Gessell A et al. Macmillan: New York, 1928.

3. Ertem IO et al. Lancet Glob Health. 2018 Mar;6(3):e279-91.

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

An analysis at a large academic health system suggests that universal screening might help to reduce problematic disparities in depression treatment.  

The study began soon after the U.S. Preventive Services Task Force recommended depression screening for all adults in 2016. The task force based this recommendation on evidence that people who are screened and treated experience fewer debilitating symptoms.

In the new research, the investigators analyzed electronic health record data following a rollout of a universal depression screening program at the University of California, San Francisco. The researchers found that the overall rate of depression screening doubled at six primary care practices over a little more than 2 years, reaching nearly 90%. The investigators presented the data April 9 at the Society of General Internal Medicine 2022 Annual Meeting in Orlando.

Meanwhile, screening disparities diminished for men, older individuals, racial and ethnic minorities, and people with language barriers – all groups that are undertreated for depression.

“It shows that if a health system is really invested, it can achieve really high depression screening,” primary investigator Maria Garcia, MD, MPH, co-director of UCSF’s Multiethnic Health Equity Research Center, told this news organization.
 

Methods for identifying depression

The health system assigned medical assistants to administer annual screening using a validated tool, the Patient Health Questionnaire-2 (PHQ-2). A “yes” response to either of its two questions triggered a longer questionnaire, the PHQ-9, used to diagnose and guide treatment.

Screening forms were available in multiple languages. Medical assistants received training on the importance of identifying depression in undertreated groups, and a banner was inserted in the electronic health record to indicate a screening was due, Dr. Garcia said.

During the rollout, a committee was assigned to monitor screening rates and adjust strategies to target disparities.

Dr. Garcia and fellow researchers calculated the likelihood of a patient being screened starting in September 2017 – when a field for depression screening status was added to the system’s electronic health record – until the rollout was completed on Dec. 31, 2019.
 

Screening disparities narrowed for all groups studied

The screening rate for patients who had a primary care visit increased from 40.5% to 88.8%. Early on, patients with language barriers were less likely to be screened than English-speaking White individuals (odds ratios, 0.55-0.59). Men were less likely to be screened than women (OR, 0.82; 95% confidence interval, 0.78-0.86), and the likelihood of being screened decreased as people got older. By 2019, screening disparities had narrowed for all groups and were only statistically significant for men (OR, 0.87; 95% CI, 0.81-0.93).

Ian Kronish, MD, MPH, a general internist and associate professor of medicine at Columbia University, New York, called the increases “impressive,” adding that the data show universal depression screening is possible in a system that serves a diverse population.

Dr. Kronish, who was not involved in this study, noted that other research indicates screening does not result in a significant reduction in depressive symptoms in the overall population. He found this to be the case in a trial he led, which focused on patients with recent cardiac events, for example.

“Given all the effort that is going into depression screening and the inclusion of depression screening as a quality metric, we need definitive randomized clinical trials testing whether depression screening leads to increased treatment uptake and, importantly, improved depressive symptoms and quality of life,” he said.

Dr. Garcia acknowledged that more work needs to be done to address treatment barriers, such as language and lack of insurance, and assess whether greater recognition of depressive symptoms in underserved groups can lead to effective treatment. “But this is an important step to know that universal depression screening narrowed disparities in screening over time,” she added.

Dr. Garcia and Dr. Kronish have disclosed no relevant financial relationships.

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

The medical news is full of articles about the coming epidemic of dementia. How many people will have it in 10 years, 20 years, etc. It’s a very legitimate concern, and I am not going to make light of it, or disagree with the predictions.

In my everyday practice, though, I find there’s an epidemic of overdiagnosed dementia, in those who aren’t even close.

This occurs in a few ways:

Aricept is pretty inexpensive these days. Long off patent, insurance companies don’t bother to question its use anymore. So anyone older than 60 who complains of losing their car keys gets put on it. Why? Because patients want their doctors to DO SOMETHING. Even if the doctor knows that there’s really nothing of alarm going on, sometimes it’s easier to go with the placebo effect than argue. I think we’ve all done that before.

There are also a lot of nonneurologists in practice who still, after almost 30 years on the market, think Aricept improves memory, when in fact that’s far from the truth. The best it can claim to do is slow down the rate at which patients get worse, but nobody wants to hear that.

I’ve also seen Aricept used for pseudodementia due to depression. Actually, I’ve seen it used for depression, too. Sometimes it’s used to counteract the side effects dof drugs that can impair cognition, such as Topamax, even in patients who aren’t even remotely demented.

None of the above are a major issue on their own. Where the trouble really happens, as with so many other things, is when they collide with an EMR, or someone too rushed to take a history, or both.

Let’s say Mrs. Jones is on Aricept because she went into a room, then forgot why she did.

Then she gets admitted to the hospital for pneumonia. Or she changes doctors and, like many practices these days, her medications are put in the computer by an MA or secretary.

A lot of times just the mention of Aricept will automatically bring the assumption that the person is demented, so that gets punched in as a diagnosis and the patient is now believed to be unable to provide a reliable history. Or the person entering the info looks up its indication and enters “Alzheimer’s disease.”

Even worse is that I’ve seen EMRs where, in an effort to save time, the computer automatically enters diagnoses as you type medications in, and it’s up to the doctor to review them for accuracy. How that saves time I have no idea. But, as above, in these cases it’s going to lead to an entry of dementia where there isn’t any.

That, in particular, is pretty scary. As I wrote here in January of this year, what happens in the EMR stays in the EMR (kind of like Las Vegas).

I’m not knocking off-label use of medications. I don’t know a doctor who doesn’t use some that way, including myself.

But when doing so leads to the wrong assumptions and diagnoses it creates a lot of problems.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The medical news is full of articles about the coming epidemic of dementia. How many people will have it in 10 years, 20 years, etc. It’s a very legitimate concern, and I am not going to make light of it, or disagree with the predictions.

In my everyday practice, though, I find there’s an epidemic of overdiagnosed dementia, in those who aren’t even close.

This occurs in a few ways:

Aricept is pretty inexpensive these days. Long off patent, insurance companies don’t bother to question its use anymore. So anyone older than 60 who complains of losing their car keys gets put on it. Why? Because patients want their doctors to DO SOMETHING. Even if the doctor knows that there’s really nothing of alarm going on, sometimes it’s easier to go with the placebo effect than argue. I think we’ve all done that before.

There are also a lot of nonneurologists in practice who still, after almost 30 years on the market, think Aricept improves memory, when in fact that’s far from the truth. The best it can claim to do is slow down the rate at which patients get worse, but nobody wants to hear that.

I’ve also seen Aricept used for pseudodementia due to depression. Actually, I’ve seen it used for depression, too. Sometimes it’s used to counteract the side effects dof drugs that can impair cognition, such as Topamax, even in patients who aren’t even remotely demented.

None of the above are a major issue on their own. Where the trouble really happens, as with so many other things, is when they collide with an EMR, or someone too rushed to take a history, or both.

Let’s say Mrs. Jones is on Aricept because she went into a room, then forgot why she did.

Then she gets admitted to the hospital for pneumonia. Or she changes doctors and, like many practices these days, her medications are put in the computer by an MA or secretary.

A lot of times just the mention of Aricept will automatically bring the assumption that the person is demented, so that gets punched in as a diagnosis and the patient is now believed to be unable to provide a reliable history. Or the person entering the info looks up its indication and enters “Alzheimer’s disease.”

Even worse is that I’ve seen EMRs where, in an effort to save time, the computer automatically enters diagnoses as you type medications in, and it’s up to the doctor to review them for accuracy. How that saves time I have no idea. But, as above, in these cases it’s going to lead to an entry of dementia where there isn’t any.

That, in particular, is pretty scary. As I wrote here in January of this year, what happens in the EMR stays in the EMR (kind of like Las Vegas).

I’m not knocking off-label use of medications. I don’t know a doctor who doesn’t use some that way, including myself.

But when doing so leads to the wrong assumptions and diagnoses it creates a lot of problems.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The medical news is full of articles about the coming epidemic of dementia. How many people will have it in 10 years, 20 years, etc. It’s a very legitimate concern, and I am not going to make light of it, or disagree with the predictions.

In my everyday practice, though, I find there’s an epidemic of overdiagnosed dementia, in those who aren’t even close.

This occurs in a few ways:

Aricept is pretty inexpensive these days. Long off patent, insurance companies don’t bother to question its use anymore. So anyone older than 60 who complains of losing their car keys gets put on it. Why? Because patients want their doctors to DO SOMETHING. Even if the doctor knows that there’s really nothing of alarm going on, sometimes it’s easier to go with the placebo effect than argue. I think we’ve all done that before.

There are also a lot of nonneurologists in practice who still, after almost 30 years on the market, think Aricept improves memory, when in fact that’s far from the truth. The best it can claim to do is slow down the rate at which patients get worse, but nobody wants to hear that.

I’ve also seen Aricept used for pseudodementia due to depression. Actually, I’ve seen it used for depression, too. Sometimes it’s used to counteract the side effects dof drugs that can impair cognition, such as Topamax, even in patients who aren’t even remotely demented.

None of the above are a major issue on their own. Where the trouble really happens, as with so many other things, is when they collide with an EMR, or someone too rushed to take a history, or both.

Let’s say Mrs. Jones is on Aricept because she went into a room, then forgot why she did.

Then she gets admitted to the hospital for pneumonia. Or she changes doctors and, like many practices these days, her medications are put in the computer by an MA or secretary.

A lot of times just the mention of Aricept will automatically bring the assumption that the person is demented, so that gets punched in as a diagnosis and the patient is now believed to be unable to provide a reliable history. Or the person entering the info looks up its indication and enters “Alzheimer’s disease.”

Even worse is that I’ve seen EMRs where, in an effort to save time, the computer automatically enters diagnoses as you type medications in, and it’s up to the doctor to review them for accuracy. How that saves time I have no idea. But, as above, in these cases it’s going to lead to an entry of dementia where there isn’t any.

That, in particular, is pretty scary. As I wrote here in January of this year, what happens in the EMR stays in the EMR (kind of like Las Vegas).

I’m not knocking off-label use of medications. I don’t know a doctor who doesn’t use some that way, including myself.

But when doing so leads to the wrong assumptions and diagnoses it creates a lot of problems.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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

Radiofrequency renal denervation provided progressive reductions in blood pressure at 3 years in patients on antihypertensive medication, but this did not translate into fewer antihypertensive drugs, new results from the SPYRAL HTN-ON MED trial show.

At 36 months, 24-hour ambulatory systolic and diastolic blood pressures were 10.0 mm Hg (P = .003) and 5.9 mm Hg (P = .005) lower, respectively, in patients who underwent renal denervation with Medtronic’s Symplicity Spyral radiofrequency catheter, compared with patients treated with a sham procedure.

The number of antihypertensive drugs, however, increased in both groups from an average of two at baseline and 6 months to three at 3 years (P = .76).

Based on the number of drugs, class, and dose, medication burden increased significantly in the sham group at 12 months (6.5 vs. 4.9; P = .04) and trended higher at 3 years (10.3 vs. 7.6; P = .26).

The procedure appeared safe, with no renal safety events in the denervation group and only three safety events overall at 36 months. One cardiovascular death occurred 693 days after a sham procedure and one patient had a hypertensive crisis and stroke 427 days after renal denervation and was discharged in stable condition, according to results published in The Lancet.

“Given the long-term safety and efficacy of renal denervation, it may provide an alternative adjunctive treatment modality in the management of hypertension,” Felix Mahfoud, MD, Saarland University Hospital, Homburg, Germany, said during a presentation of the study at the recent American College of Cardiology (ACC) 2022 Scientific Session.

Ted Bosworth/MDedge News

Sham-controlled evidence

As previously reported, significant BP reductions at 6 months in SPYRAL HTN-ON provided proof of concept and helped revive enthusiasm for the procedure after failing to meet the primary endpoint in the SYMPLICITY HTN-3 trial. Results from the Global SYMPLICITY Registry have shown benefits out to 3 years, but sham-controlled data have been lacking.

The trial enrolled 80 patients with an office systolic BP of 150-180 mm Hg and diastolic of 90 mm Hg or greater and 24-hour ambulatory systolic BP of 140-170 mm Hg, who were on up to three antihypertensive medications.

Medication changes were allowed beginning at 6 months; patients and physicians were unblinded at 12 months. Between 24 and 36 months, 13 patients assigned to the sham procedure crossed over to denervation treatment. Medication adherence at 3 years was 77% in the denervation group versus 93% in the sham group.

At 3 years, the renal denervation group had significantly greater reductions from baseline in several ambulatory BP measures, compared with the sham group, including: 24-hour systolic (10.0 mm Hg), morning systolic (11.0 mm Hg), daytime systolic (8.9 mm Hg), and night-time systolic (11.8 mm Hg).

Renal denervation led to an 8.2 mm Hg greater fall in office systolic BP, but this failed to reach statistical significance (P = .07).

Almost twice as many patients in the denervation group achieved a 24-hour systolic BP less than 140 mm Hg than in the sham group (83.3%, vs. 43.8%; P = .002), Dr. Mahfoud reported.

“Although renal denervation appears to effectively lower blood pressure, participants in the renal denervation group did not quite reach guideline-recommended blood pressure thresholds,” Harini Sarathy, MD, University of California, San Francisco, and Liann Abu Salman, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, point out in an accompanying editorial. “This result could have been due to a degree of physician inertia or differential prescribing of blood pressure medications for the intervention group, compared with the sham control group, wherein physicians might have considered renal denervation to be the fourth antihypertensive medication.”

The editorialists also note that nearly a third of the sham group (13 of 42) underwent renal denervation. “The differentially missing BP readings at 24 months for the sham group are a cause for concern, although the absence of any meaningful differences in results after imputation is somewhat reassuring.”

A 10 mm Hg reduction in BP after 36 months would be expected to translate to a significant reduction in cardiovascular outcomes, they say. The sustained reductions in several systolic readings also speak to the “always-on distinctiveness” that renal denervation proponents claim.

“In the stark absence of novel antihypertensive drug development, renal denervation is seemingly poised to be an effective supplement, if not an alternative, to complex antihypertensive regimens with frequent dosing schedules,” they conclude. “We look forward to results of the Expansion trial in providing more definitive answers regarding whether this translates to meaningful protection from target organ damage.”

Dr. Mahfoud observed that BP control worsened during the COVID-19 pandemic, which may have impacted BP results, but that in-person follow-up visits were still performed. Other limitations are a lack of information on patients’ exercise, diet, and smoking habits and that blood and urine testing assessed medication adherence at discrete time points, but adherence over an extended period of time is uncertain.

Dr. Mahfoud reports research grants from Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Kardiologie and scientific support and speaker honoraria from Bayer, Boehringer Ingelheim, Medtronic, Merck, and ReCor Medical. The study was funded by Medtronic. Dr. Sarathy and Dr. Salman report no relevant financial relationships.

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