Primary Care/Internal Medicine

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

Osteoporosis is defined by a clinically diagnosed fragility fracture or a bone mineral density (BMD) of at least 2.5 SD below the mean for young female adults, usually measured by dual-energy x-ray absorptiometry. Risk factors include age, female sex, post-menopause, hypogonadism or premature ovarian failure, history of cigarette smoking or alcohol consumption (3 or more drinks daily), rheumatoid arthritis, or medications including glucocorticoids, anticoagulants, anticonvulsants, and aromatase inhibitors.

This guideline update focuses on treatment with bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) and denosumab. Denosumab, a human monoclonal antibody against RANK-ligand, approved by the Food and Drug Administration for treatment of osteoporosis, has been added to the list of allowed medications since publication of the 2008 guideline. Several therapies have been excluded from the update, including calcitonin, which is no longer widely used for osteoporosis treatment, and etidronate and pamidronate, neither of which are FDA-approved for the prevention of fractures or treatment of osteoporosis. It should be noted that the evidence continues to be insufficient regarding the effectiveness of therapies to prevent fractures or to treat osteoporosis in men.

Bottom line:

Clinicians should offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk of hip and vertebral fractures in women who have known osteoporosis diagnosed as a T score less than –2.5 or those with a fragility fracture. Pharmacologic therapy should be used for 5 years; however, high risk patients may benefit from longer treatment. There is no benefit to bone density monitoring during the 5-year pharmacologic treatment period. In addition, bisphosphonates should be considered in men who have clinically recognized osteoporosis.

Reference:

Qaseem, A, Forciea, MA, McLean RM, Denberg TD. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Int Med. 2017;166(11):818-39.
 

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Meizinger is a second year resident in the Family Medicine Residency Program at Abington Jefferson Health.

Chronic obstructive lung disease (COPD) is the third leading cause of death in the United States¹ and a major cause of mortality and morbidity around the world. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) released a new “2017 Report”² with modified recommendations for the diagnosis, management, and prevention of COPD. The report contains several changes that are relevant to the primary care provider that will be outlined below.

Redefining COPD

GOLD’s definition of COPD was changed in its 2017 Report: “COPD is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitations that are due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” The report emphasizes that “COPD may be punctuated by periods of acute worsening of respiratory symptoms, called exacerbations.” Note that the terms “emphysema” and “chronic bronchitis” have been removed in favor of a more comprehensive description of the pathophysiology of COPD. Importantly, the report states that cough and sputum production for at least 3 months in each of 2 consecutive years, previously accepted as diagnostic criteria, are present in only a minority of patients. It is noted that chronic respiratory symptoms may exist without spirometric changes and many patients (usually smokers) have structural evidence of COPD without airflow limitation.

Changes to COPD initial assessment

The primary criterion for diagnosis is unchanged: post-bronchodilator forced expiratory volume in 1 second (FEV₁₎/forced vital capacity (FVC) less than 0.70. Spirometry remains important to confirm the diagnosis in those with classic symptoms of dyspnea, chronic cough, and/or sputum production with a history of exposure to noxious particles or gases.

The GOLD assessment system previously incorporated spirometry and included an “ABCD” system such that patients in group A are least severe. Spirometry has been progressively deemphasized in favor of symptom-based classification and the 2017 Report, for the first time, dissociates spirometric findings from severity classification.

The new system uses symptom severity and exacerbation risk to classify COPD. Two specific standardized COPD symptom measurement tools, The Modified British Medical Research Council (mMRC) questionnaire and COPD Assessment Test (CAT), are reported by GOLD as the most widely used. Low symptom severity is considered an mMRC less than or equal to 1 or CAT less than or equal to 9, high symptom severity is considered an mMRC greater than or equal to 2 or CAT greater than or equal to 10. Low risk of exacerbation is defined as no more than one exacerbation not resulting in hospital admission in the last 12 months; high risk of exacerbation is defined as at least two exacerbations or any exacerbations resulting in hospital admission in the last 12 months. Symptom severity and exacerbation risk is divided into four quadrants:
 

• GOLD group A: Low symptom severity, low exacerbation risk.

• GOLD group B: High symptom severity, low exacerbation risk.

• GOLD group C: Low symptom severity, high exacerbation risk.

• GOLD group D: High symptom severity, high exacerbation risk.

Changes to prevention and management of stable COPD

Smoking cessation remains important in the prevention of COPD. The 2017 Report reflects the U.S. Preventive Services Task Force’s guidelines for smoking cessation: Offer nicotine replacement, cessation counseling, and pharmacotherapy (varenicline, bupropion or nortriptyline). There is insufficient evidence to support the use of e-cigarettes. Influenza and pneumococcal vaccinations are recommended. Pulmonary rehabilitation remains important.

The 2017 Report includes an expanded discussion of COPD medications. The role of short-acting bronchodilators (SABD) in COPD remains prominent. Changes include a stronger recommendation to use combination short-acting beta-agonists and short-acting muscarinic antagonists (SABA/SAMA) as these seem to be superior to SABD monotherapy in improving symptoms and FEV₁.

There were several changes to the pharmacologic treatment algorithm. For the first time, GOLD proposes escalation strategies. Preference is given to LABA/LAMA (long-acting beta-agonist/long-acting muscarinic antagonists) combinations over LABA/ICS (long-acting beta-agonist/inhaled corticosteroid) combinations as a mainstay of treatment. The rationale for this change is that LABA/LAMAs give greater bronchodilation compared with LABA/ICS, and one study showed a decreased rate of exacerbations compared to LABA/ICS in patients with a history of exacerbations. In addition, patients with COPD who receive ICS appear to have a higher risk of developing pneumonia. GOLD recommendations are:

• Group A: Start with single bronchodilator (short- or long-acting), escalate to alternative class of bronchodilator if necessary.

• Group B: Start with LABA or LAMA, escalate to LABA/LAMA if symptoms persist.

• Group C: Start with LAMA, escalate to LABA/LAMA (preferred) or LABA/ICS if exacerbations continue.

• Group D: Start with LABA/LAMA (preferred) or LAMA monotherapy, escalate to LABA/LAMA/ICS (preferred) or try LABA/ICS before escalating to LAMA/LABA/ICS if symptoms persist or exacerbations continue; roflumilast and/or a macrolide may be considered if further exacerbations occur with LABA/LAMA/ICS.
 

Bottom line

1. GOLD classification of COPD severity is now based on clinical criteria alone: symptom assessment and risk for exacerbation.

2. SABA/SAMA combination therapy seems to be superior to either SABA or SAMA alone.

3. Patients in group A (milder symptoms, low exacerbation risk) may be initiated on either short- or long-acting bronchodilator therapy.

4. Patients in group B (milder symptoms, increased exacerbation risk) should be initiated on LAMA monotherapy.

5. LABA/LAMA combination therapy seems to be superior to LABA/ICS combination therapy and should be used when long-acting bronchodilator monotherapy fails to control symptoms or reduce exacerbations.

References

1. CDC MMWR 11/23/12

2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 at http://goldcopd.org (accessed 3/10/2017)
 

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Lent is chief resident in the program.

Chronic obstructive lung disease (COPD) is the third leading cause of death in the United States¹ and a major cause of mortality and morbidity around the world. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) released a new “2017 Report”² with modified recommendations for the diagnosis, management, and prevention of COPD. The report contains several changes that are relevant to the primary care provider that will be outlined below.

Redefining COPD

GOLD’s definition of COPD was changed in its 2017 Report: “COPD is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitations that are due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” The report emphasizes that “COPD may be punctuated by periods of acute worsening of respiratory symptoms, called exacerbations.” Note that the terms “emphysema” and “chronic bronchitis” have been removed in favor of a more comprehensive description of the pathophysiology of COPD. Importantly, the report states that cough and sputum production for at least 3 months in each of 2 consecutive years, previously accepted as diagnostic criteria, are present in only a minority of patients. It is noted that chronic respiratory symptoms may exist without spirometric changes and many patients (usually smokers) have structural evidence of COPD without airflow limitation.

Changes to COPD initial assessment

The primary criterion for diagnosis is unchanged: post-bronchodilator forced expiratory volume in 1 second (FEV₁₎/forced vital capacity (FVC) less than 0.70. Spirometry remains important to confirm the diagnosis in those with classic symptoms of dyspnea, chronic cough, and/or sputum production with a history of exposure to noxious particles or gases.

The GOLD assessment system previously incorporated spirometry and included an “ABCD” system such that patients in group A are least severe. Spirometry has been progressively deemphasized in favor of symptom-based classification and the 2017 Report, for the first time, dissociates spirometric findings from severity classification.

The new system uses symptom severity and exacerbation risk to classify COPD. Two specific standardized COPD symptom measurement tools, The Modified British Medical Research Council (mMRC) questionnaire and COPD Assessment Test (CAT), are reported by GOLD as the most widely used. Low symptom severity is considered an mMRC less than or equal to 1 or CAT less than or equal to 9, high symptom severity is considered an mMRC greater than or equal to 2 or CAT greater than or equal to 10. Low risk of exacerbation is defined as no more than one exacerbation not resulting in hospital admission in the last 12 months; high risk of exacerbation is defined as at least two exacerbations or any exacerbations resulting in hospital admission in the last 12 months. Symptom severity and exacerbation risk is divided into four quadrants:
 

• GOLD group A: Low symptom severity, low exacerbation risk.

• GOLD group B: High symptom severity, low exacerbation risk.

• GOLD group C: Low symptom severity, high exacerbation risk.

• GOLD group D: High symptom severity, high exacerbation risk.

Changes to prevention and management of stable COPD

Smoking cessation remains important in the prevention of COPD. The 2017 Report reflects the U.S. Preventive Services Task Force’s guidelines for smoking cessation: Offer nicotine replacement, cessation counseling, and pharmacotherapy (varenicline, bupropion or nortriptyline). There is insufficient evidence to support the use of e-cigarettes. Influenza and pneumococcal vaccinations are recommended. Pulmonary rehabilitation remains important.

The 2017 Report includes an expanded discussion of COPD medications. The role of short-acting bronchodilators (SABD) in COPD remains prominent. Changes include a stronger recommendation to use combination short-acting beta-agonists and short-acting muscarinic antagonists (SABA/SAMA) as these seem to be superior to SABD monotherapy in improving symptoms and FEV₁.

There were several changes to the pharmacologic treatment algorithm. For the first time, GOLD proposes escalation strategies. Preference is given to LABA/LAMA (long-acting beta-agonist/long-acting muscarinic antagonists) combinations over LABA/ICS (long-acting beta-agonist/inhaled corticosteroid) combinations as a mainstay of treatment. The rationale for this change is that LABA/LAMAs give greater bronchodilation compared with LABA/ICS, and one study showed a decreased rate of exacerbations compared to LABA/ICS in patients with a history of exacerbations. In addition, patients with COPD who receive ICS appear to have a higher risk of developing pneumonia. GOLD recommendations are:

• Group A: Start with single bronchodilator (short- or long-acting), escalate to alternative class of bronchodilator if necessary.

• Group B: Start with LABA or LAMA, escalate to LABA/LAMA if symptoms persist.

• Group C: Start with LAMA, escalate to LABA/LAMA (preferred) or LABA/ICS if exacerbations continue.

• Group D: Start with LABA/LAMA (preferred) or LAMA monotherapy, escalate to LABA/LAMA/ICS (preferred) or try LABA/ICS before escalating to LAMA/LABA/ICS if symptoms persist or exacerbations continue; roflumilast and/or a macrolide may be considered if further exacerbations occur with LABA/LAMA/ICS.
 

Bottom line

1. GOLD classification of COPD severity is now based on clinical criteria alone: symptom assessment and risk for exacerbation.

2. SABA/SAMA combination therapy seems to be superior to either SABA or SAMA alone.

3. Patients in group A (milder symptoms, low exacerbation risk) may be initiated on either short- or long-acting bronchodilator therapy.

4. Patients in group B (milder symptoms, increased exacerbation risk) should be initiated on LAMA monotherapy.

5. LABA/LAMA combination therapy seems to be superior to LABA/ICS combination therapy and should be used when long-acting bronchodilator monotherapy fails to control symptoms or reduce exacerbations.

References

1. CDC MMWR 11/23/12

2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 at http://goldcopd.org (accessed 3/10/2017)
 

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Lent is chief resident in the program.

Chronic obstructive lung disease (COPD) is the third leading cause of death in the United States¹ and a major cause of mortality and morbidity around the world. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) released a new “2017 Report”² with modified recommendations for the diagnosis, management, and prevention of COPD. The report contains several changes that are relevant to the primary care provider that will be outlined below.

Redefining COPD

GOLD’s definition of COPD was changed in its 2017 Report: “COPD is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitations that are due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” The report emphasizes that “COPD may be punctuated by periods of acute worsening of respiratory symptoms, called exacerbations.” Note that the terms “emphysema” and “chronic bronchitis” have been removed in favor of a more comprehensive description of the pathophysiology of COPD. Importantly, the report states that cough and sputum production for at least 3 months in each of 2 consecutive years, previously accepted as diagnostic criteria, are present in only a minority of patients. It is noted that chronic respiratory symptoms may exist without spirometric changes and many patients (usually smokers) have structural evidence of COPD without airflow limitation.

Changes to COPD initial assessment

The primary criterion for diagnosis is unchanged: post-bronchodilator forced expiratory volume in 1 second (FEV₁₎/forced vital capacity (FVC) less than 0.70. Spirometry remains important to confirm the diagnosis in those with classic symptoms of dyspnea, chronic cough, and/or sputum production with a history of exposure to noxious particles or gases.

The GOLD assessment system previously incorporated spirometry and included an “ABCD” system such that patients in group A are least severe. Spirometry has been progressively deemphasized in favor of symptom-based classification and the 2017 Report, for the first time, dissociates spirometric findings from severity classification.

The new system uses symptom severity and exacerbation risk to classify COPD. Two specific standardized COPD symptom measurement tools, The Modified British Medical Research Council (mMRC) questionnaire and COPD Assessment Test (CAT), are reported by GOLD as the most widely used. Low symptom severity is considered an mMRC less than or equal to 1 or CAT less than or equal to 9, high symptom severity is considered an mMRC greater than or equal to 2 or CAT greater than or equal to 10. Low risk of exacerbation is defined as no more than one exacerbation not resulting in hospital admission in the last 12 months; high risk of exacerbation is defined as at least two exacerbations or any exacerbations resulting in hospital admission in the last 12 months. Symptom severity and exacerbation risk is divided into four quadrants:
 

• GOLD group A: Low symptom severity, low exacerbation risk.

• GOLD group B: High symptom severity, low exacerbation risk.

• GOLD group C: Low symptom severity, high exacerbation risk.

• GOLD group D: High symptom severity, high exacerbation risk.

Changes to prevention and management of stable COPD

Smoking cessation remains important in the prevention of COPD. The 2017 Report reflects the U.S. Preventive Services Task Force’s guidelines for smoking cessation: Offer nicotine replacement, cessation counseling, and pharmacotherapy (varenicline, bupropion or nortriptyline). There is insufficient evidence to support the use of e-cigarettes. Influenza and pneumococcal vaccinations are recommended. Pulmonary rehabilitation remains important.

The 2017 Report includes an expanded discussion of COPD medications. The role of short-acting bronchodilators (SABD) in COPD remains prominent. Changes include a stronger recommendation to use combination short-acting beta-agonists and short-acting muscarinic antagonists (SABA/SAMA) as these seem to be superior to SABD monotherapy in improving symptoms and FEV₁.

There were several changes to the pharmacologic treatment algorithm. For the first time, GOLD proposes escalation strategies. Preference is given to LABA/LAMA (long-acting beta-agonist/long-acting muscarinic antagonists) combinations over LABA/ICS (long-acting beta-agonist/inhaled corticosteroid) combinations as a mainstay of treatment. The rationale for this change is that LABA/LAMAs give greater bronchodilation compared with LABA/ICS, and one study showed a decreased rate of exacerbations compared to LABA/ICS in patients with a history of exacerbations. In addition, patients with COPD who receive ICS appear to have a higher risk of developing pneumonia. GOLD recommendations are:

• Group A: Start with single bronchodilator (short- or long-acting), escalate to alternative class of bronchodilator if necessary.

• Group B: Start with LABA or LAMA, escalate to LABA/LAMA if symptoms persist.

• Group C: Start with LAMA, escalate to LABA/LAMA (preferred) or LABA/ICS if exacerbations continue.

• Group D: Start with LABA/LAMA (preferred) or LAMA monotherapy, escalate to LABA/LAMA/ICS (preferred) or try LABA/ICS before escalating to LAMA/LABA/ICS if symptoms persist or exacerbations continue; roflumilast and/or a macrolide may be considered if further exacerbations occur with LABA/LAMA/ICS.
 

Bottom line

1. GOLD classification of COPD severity is now based on clinical criteria alone: symptom assessment and risk for exacerbation.

2. SABA/SAMA combination therapy seems to be superior to either SABA or SAMA alone.

3. Patients in group A (milder symptoms, low exacerbation risk) may be initiated on either short- or long-acting bronchodilator therapy.

4. Patients in group B (milder symptoms, increased exacerbation risk) should be initiated on LAMA monotherapy.

5. LABA/LAMA combination therapy seems to be superior to LABA/ICS combination therapy and should be used when long-acting bronchodilator monotherapy fails to control symptoms or reduce exacerbations.

References

1. CDC MMWR 11/23/12

2. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 at http://goldcopd.org (accessed 3/10/2017)
 

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Lent is chief resident in the program.

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).

However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.

When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.

For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”

For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.

Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.

For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.

The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.

The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.

Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”

Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.

The AGA Institute issued a clinical practice update for managing hepatitis C virus–infected patients who achieve a sustained virologic response after antiviral therapy, who still require ongoing care for their liver disease. The expert review appears in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.018).

Even though direct-acting antiviral regimens have produced remarkably high sustained virologic response (SVR) rates and it appears that fewer than 1% of patients relapse, and even though liver fibrosis and cirrhosis may regress with this therapy, continued surveillance and even intervention may be needed “to reduce complications arising from liver damage that has already accrued by the time SVR was attained,” said Ira M. Jacobson, MD, AGAF, chair of the department of medicine, Mount Sinai Beth Israel Medical Center, New York, and his associates.

BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.

Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.

Sharon Worcester/Frontline Medical News

Sharon Worcester/Frontline Medical News

sworcester@frontlinemedcom.com

BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.

Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.

Sharon Worcester/Frontline Medical News

Sharon Worcester/Frontline Medical News

sworcester@frontlinemedcom.com

BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.

Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.

Sharon Worcester/Frontline Medical News

Sharon Worcester/Frontline Medical News

sworcester@frontlinemedcom.com

ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.

The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.

Sharon Worcester/Frontline Medical News

COMFORT-1 update: ruxolitinib responses durable in myelofibrosis

To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.

The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.

A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.

“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.

At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.

Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.

“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.

Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.

Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).

However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.

Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.

sworcester@frontlinemedcom.com

ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.

The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.

Sharon Worcester/Frontline Medical News

COMFORT-1 update: ruxolitinib responses durable in myelofibrosis

To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.

The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.

A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.

“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.

At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.

Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.

“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.

Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.

Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).

However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.

Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.

sworcester@frontlinemedcom.com

ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.

The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.

Sharon Worcester/Frontline Medical News

COMFORT-1 update: ruxolitinib responses durable in myelofibrosis

To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.

The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.

A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.

“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.

At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.

Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.

“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.

Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.

Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).

However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.

Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.

sworcester@frontlinemedcom.com

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”

An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.

The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.

The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.

But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”

They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.

Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”

Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.

As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.

Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”

Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.” 

Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”

Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”

But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”

Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.

“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”

Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”

Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.

One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.

“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.

But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.

Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.

However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.

There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).

Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).

In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.

Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.

However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.

There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).

Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).

In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.

Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.

The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.

The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.

However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.

There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).

Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).

In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.

Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.

Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.

The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).

Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.

“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.

Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.

The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.

Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.

The USPSTF members reported having no relevant financial conflicts.

Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.

The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).

Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.

“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.

Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.

The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.

Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.

The USPSTF members reported having no relevant financial conflicts.

Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.

The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).

Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.

“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.

Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.

The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.

Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.

The USPSTF members reported having no relevant financial conflicts.