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NPH insulin: It remains a good option
ILLUSTRATIVE CASE
Blanche is a 54-year-old overweight woman who has had type 2 diabetes mellitus (T2DM) for 5 years. She has been optimized on both metformin (1000 mg bid) and exenatide (2 mg weekly). While taking these medications, her hemoglobin A1C (HbA1C) has dropped from 11.2 to 8.4, and her body mass index (BMI) has declined from 35 to 31. However, she is still not at goal. You decide to start her on long-acting basal insulin. She has limited income, and she currently spends $75/month for her metformin, exenatide, atorvastatin, and lisinopril. What insulin do you prescribe?
The Centers for Disease Control and Prevention (CDC) reported that the prevalence of diabetes in the United States was 9.4% (30.3 million people) in 2015.2 Among those affected, approximately 95.8% had T2DM.2 The same report estimated that 1.5 million new cases of diabetes (6.7 per 1000 persons) were diagnosed annually among US adults ≥ 18 years of age, and that about $7900 of annual medical expenses for patients diagnosed with diabetes was directly attributable to diabetes.2
In the United States, neutral protamine Hagedorn (NPH) insulin was the most commonly used intermediate- to long-acting insulin until the introduction of the long-acting insulin analogs (insulin glargine in 2000 and insulin detemir in 2005).3 Despite being considerably more expensive than NPH insulin, long-acting insulin analogs had captured more than 80% of the total long-acting insulin market by 2010.4 The market share for NPH insulin dropped from 81.9% in 2001 to 16.2% in 2010.4
While the newer insulin analogs are significantly more expensive than NPH insulin, with higher corresponding out-of-pocket costs to patients, researchers have had a difficult time demonstrating greater effectiveness or any definitive differences in any long-term outcomes between NPH and the insulin analogs. A 2007 Cochrane review comparing NPH insulin to both glargine and detemir showed little difference in metabolic control (as measured by HbA1C) or in the rate of severe hypoglycemia. However, the rates of symptomatic, overall, and nocturnal hypoglycemia were statistically lower with the insulin analogs.5
A 2015 retrospective observational study from the Veterans Health Administration (N = 142,940) covering a 10-year period from 2000 to 2010 found no consistent differences in long-term health outcomes when comparing the use of long-acting insulin analogs to that of NPH insulin.3,6
STUDY SUMMARY
Study compares performance of basal insulin analogs to that of NPH
This retrospective, observational study included 25,489 adult patients with T2DM who were enrolled in Kaiser Permanente of Northern California, had full medical and prescription coverage, and initiated basal insulin therapy with either NPH or an insulin analog between 2006 and 2015.
The primary outcome was the time from basal insulin therapy initiation to a hypoglycemia-related emergency department (ED) visit or hospital admission. The secondary outcome was the change in HbA1C level within 1 year of initiation of basal insulin therapy.
Continue to: Per 1000 person-years...
Per 1000 person-years, there was no significant difference in hypoglycemia-related ED visits or hospital admissions between the analog and NPH groups (11.9 events vs 8.8 events, respectively; between-group difference, 3.1 events; 95% confidence interval [CI], –1.5 to 7.7). HbA1C reduction was statistically greater with NPH, but most likely not clinically significant between insulin analogs and NPH (1.26 vs 1.48 percentage points; between group difference, –0.22%; 95% CI, –0.09% to –0.37%).
WHAT’S NEW?
No clinically relevant differences between insulin analogs and NPH
This study revealed that there is no clinically relevant difference in HbA1C levels and no difference in patient-focused outcomes of hypoglycemia-related ED visits or hospital admissions between NPH insulin and the more expensive insulin analogs. This makes a strong case for a different approach to initial basal insulin therapy for patients with T2DM who need insulin for glucose control.
CAVEATS
Demographics and less severe hypoglycemia might be at issue
This retrospective, observational study has broad demographics (but moderate under-representation of African-Americans), minimal patient health care disparities, and good access to medications. But generalizability outside of an integrated health delivery system may be limited. The study design also is subject to confounding, as not all potential impacts on the results can be corrected for or controlled in an observational study. Also, less profound hypoglycemia that did not require an ED visit or hospital admission was not captured.
CHALLENGES TO IMPLEMENTATION
Convenience and marketing factors may hinder change
Insulin analogs may have a number of convenience and marketing factors that may make it hard for providers and systems to change and use more NPH. However, the easy-to-use insulin analog pens are matched in availability and convenience by the much less advertised NPH insulin pens produced by at least 3 major pharmaceutical companies. In addition, while the overall cost for the insulin analogs continues to be 2 to 3 times that of non-human NPH insulin, insurance often covers up to, or more than, 80% of the cost of the insulin analogs, making the difference in the patient’s copay between the 2 not as severe. For example, patients may pay $30 to $40 per month for insulin analogs vs $10 to $25 per month for cheaper versions of NPH.7,8
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Lipska KJ, Parker MM, Moffet HH, et al. Association of initiation of basal insulin analogs vs neutral protamine Hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320:53-62.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2017. www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed January 15, 2020.
3. Prentice JC, Conlin PR, Gellad WF, et al. Long-term outcomes of analogue insulin compared with NPH for patients with type 2 diabetes mellitus. Am J Manag Care. 2015;21:e235-e243.
4. Turner LW, Nartey D, Stafford RS, et al. Ambulatory treatment of type 2 diabetes in the U.S., 1997-2012. Diabetes Care. 2014;37:985-992.
5. Horvath K, Jeitler K, Berghold A, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(2):CD005613.
6. Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med. 2017;166:572-578.
7. GoodRx.com. Insulins. www.goodrx.com/insulins. Accessed January 20, 2020. 8. Cefalu WT, Dawes DE, Gavlak G, et al. Insulin access and affordability working group: conclusions and recommendations. Diabetes Care. 2018;41:1299-1311.
ILLUSTRATIVE CASE
Blanche is a 54-year-old overweight woman who has had type 2 diabetes mellitus (T2DM) for 5 years. She has been optimized on both metformin (1000 mg bid) and exenatide (2 mg weekly). While taking these medications, her hemoglobin A1C (HbA1C) has dropped from 11.2 to 8.4, and her body mass index (BMI) has declined from 35 to 31. However, she is still not at goal. You decide to start her on long-acting basal insulin. She has limited income, and she currently spends $75/month for her metformin, exenatide, atorvastatin, and lisinopril. What insulin do you prescribe?
The Centers for Disease Control and Prevention (CDC) reported that the prevalence of diabetes in the United States was 9.4% (30.3 million people) in 2015.2 Among those affected, approximately 95.8% had T2DM.2 The same report estimated that 1.5 million new cases of diabetes (6.7 per 1000 persons) were diagnosed annually among US adults ≥ 18 years of age, and that about $7900 of annual medical expenses for patients diagnosed with diabetes was directly attributable to diabetes.2
In the United States, neutral protamine Hagedorn (NPH) insulin was the most commonly used intermediate- to long-acting insulin until the introduction of the long-acting insulin analogs (insulin glargine in 2000 and insulin detemir in 2005).3 Despite being considerably more expensive than NPH insulin, long-acting insulin analogs had captured more than 80% of the total long-acting insulin market by 2010.4 The market share for NPH insulin dropped from 81.9% in 2001 to 16.2% in 2010.4
While the newer insulin analogs are significantly more expensive than NPH insulin, with higher corresponding out-of-pocket costs to patients, researchers have had a difficult time demonstrating greater effectiveness or any definitive differences in any long-term outcomes between NPH and the insulin analogs. A 2007 Cochrane review comparing NPH insulin to both glargine and detemir showed little difference in metabolic control (as measured by HbA1C) or in the rate of severe hypoglycemia. However, the rates of symptomatic, overall, and nocturnal hypoglycemia were statistically lower with the insulin analogs.5
A 2015 retrospective observational study from the Veterans Health Administration (N = 142,940) covering a 10-year period from 2000 to 2010 found no consistent differences in long-term health outcomes when comparing the use of long-acting insulin analogs to that of NPH insulin.3,6
STUDY SUMMARY
Study compares performance of basal insulin analogs to that of NPH
This retrospective, observational study included 25,489 adult patients with T2DM who were enrolled in Kaiser Permanente of Northern California, had full medical and prescription coverage, and initiated basal insulin therapy with either NPH or an insulin analog between 2006 and 2015.
The primary outcome was the time from basal insulin therapy initiation to a hypoglycemia-related emergency department (ED) visit or hospital admission. The secondary outcome was the change in HbA1C level within 1 year of initiation of basal insulin therapy.
Continue to: Per 1000 person-years...
Per 1000 person-years, there was no significant difference in hypoglycemia-related ED visits or hospital admissions between the analog and NPH groups (11.9 events vs 8.8 events, respectively; between-group difference, 3.1 events; 95% confidence interval [CI], –1.5 to 7.7). HbA1C reduction was statistically greater with NPH, but most likely not clinically significant between insulin analogs and NPH (1.26 vs 1.48 percentage points; between group difference, –0.22%; 95% CI, –0.09% to –0.37%).
WHAT’S NEW?
No clinically relevant differences between insulin analogs and NPH
This study revealed that there is no clinically relevant difference in HbA1C levels and no difference in patient-focused outcomes of hypoglycemia-related ED visits or hospital admissions between NPH insulin and the more expensive insulin analogs. This makes a strong case for a different approach to initial basal insulin therapy for patients with T2DM who need insulin for glucose control.
CAVEATS
Demographics and less severe hypoglycemia might be at issue
This retrospective, observational study has broad demographics (but moderate under-representation of African-Americans), minimal patient health care disparities, and good access to medications. But generalizability outside of an integrated health delivery system may be limited. The study design also is subject to confounding, as not all potential impacts on the results can be corrected for or controlled in an observational study. Also, less profound hypoglycemia that did not require an ED visit or hospital admission was not captured.
CHALLENGES TO IMPLEMENTATION
Convenience and marketing factors may hinder change
Insulin analogs may have a number of convenience and marketing factors that may make it hard for providers and systems to change and use more NPH. However, the easy-to-use insulin analog pens are matched in availability and convenience by the much less advertised NPH insulin pens produced by at least 3 major pharmaceutical companies. In addition, while the overall cost for the insulin analogs continues to be 2 to 3 times that of non-human NPH insulin, insurance often covers up to, or more than, 80% of the cost of the insulin analogs, making the difference in the patient’s copay between the 2 not as severe. For example, patients may pay $30 to $40 per month for insulin analogs vs $10 to $25 per month for cheaper versions of NPH.7,8
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
Blanche is a 54-year-old overweight woman who has had type 2 diabetes mellitus (T2DM) for 5 years. She has been optimized on both metformin (1000 mg bid) and exenatide (2 mg weekly). While taking these medications, her hemoglobin A1C (HbA1C) has dropped from 11.2 to 8.4, and her body mass index (BMI) has declined from 35 to 31. However, she is still not at goal. You decide to start her on long-acting basal insulin. She has limited income, and she currently spends $75/month for her metformin, exenatide, atorvastatin, and lisinopril. What insulin do you prescribe?
The Centers for Disease Control and Prevention (CDC) reported that the prevalence of diabetes in the United States was 9.4% (30.3 million people) in 2015.2 Among those affected, approximately 95.8% had T2DM.2 The same report estimated that 1.5 million new cases of diabetes (6.7 per 1000 persons) were diagnosed annually among US adults ≥ 18 years of age, and that about $7900 of annual medical expenses for patients diagnosed with diabetes was directly attributable to diabetes.2
In the United States, neutral protamine Hagedorn (NPH) insulin was the most commonly used intermediate- to long-acting insulin until the introduction of the long-acting insulin analogs (insulin glargine in 2000 and insulin detemir in 2005).3 Despite being considerably more expensive than NPH insulin, long-acting insulin analogs had captured more than 80% of the total long-acting insulin market by 2010.4 The market share for NPH insulin dropped from 81.9% in 2001 to 16.2% in 2010.4
While the newer insulin analogs are significantly more expensive than NPH insulin, with higher corresponding out-of-pocket costs to patients, researchers have had a difficult time demonstrating greater effectiveness or any definitive differences in any long-term outcomes between NPH and the insulin analogs. A 2007 Cochrane review comparing NPH insulin to both glargine and detemir showed little difference in metabolic control (as measured by HbA1C) or in the rate of severe hypoglycemia. However, the rates of symptomatic, overall, and nocturnal hypoglycemia were statistically lower with the insulin analogs.5
A 2015 retrospective observational study from the Veterans Health Administration (N = 142,940) covering a 10-year period from 2000 to 2010 found no consistent differences in long-term health outcomes when comparing the use of long-acting insulin analogs to that of NPH insulin.3,6
STUDY SUMMARY
Study compares performance of basal insulin analogs to that of NPH
This retrospective, observational study included 25,489 adult patients with T2DM who were enrolled in Kaiser Permanente of Northern California, had full medical and prescription coverage, and initiated basal insulin therapy with either NPH or an insulin analog between 2006 and 2015.
The primary outcome was the time from basal insulin therapy initiation to a hypoglycemia-related emergency department (ED) visit or hospital admission. The secondary outcome was the change in HbA1C level within 1 year of initiation of basal insulin therapy.
Continue to: Per 1000 person-years...
Per 1000 person-years, there was no significant difference in hypoglycemia-related ED visits or hospital admissions between the analog and NPH groups (11.9 events vs 8.8 events, respectively; between-group difference, 3.1 events; 95% confidence interval [CI], –1.5 to 7.7). HbA1C reduction was statistically greater with NPH, but most likely not clinically significant between insulin analogs and NPH (1.26 vs 1.48 percentage points; between group difference, –0.22%; 95% CI, –0.09% to –0.37%).
WHAT’S NEW?
No clinically relevant differences between insulin analogs and NPH
This study revealed that there is no clinically relevant difference in HbA1C levels and no difference in patient-focused outcomes of hypoglycemia-related ED visits or hospital admissions between NPH insulin and the more expensive insulin analogs. This makes a strong case for a different approach to initial basal insulin therapy for patients with T2DM who need insulin for glucose control.
CAVEATS
Demographics and less severe hypoglycemia might be at issue
This retrospective, observational study has broad demographics (but moderate under-representation of African-Americans), minimal patient health care disparities, and good access to medications. But generalizability outside of an integrated health delivery system may be limited. The study design also is subject to confounding, as not all potential impacts on the results can be corrected for or controlled in an observational study. Also, less profound hypoglycemia that did not require an ED visit or hospital admission was not captured.
CHALLENGES TO IMPLEMENTATION
Convenience and marketing factors may hinder change
Insulin analogs may have a number of convenience and marketing factors that may make it hard for providers and systems to change and use more NPH. However, the easy-to-use insulin analog pens are matched in availability and convenience by the much less advertised NPH insulin pens produced by at least 3 major pharmaceutical companies. In addition, while the overall cost for the insulin analogs continues to be 2 to 3 times that of non-human NPH insulin, insurance often covers up to, or more than, 80% of the cost of the insulin analogs, making the difference in the patient’s copay between the 2 not as severe. For example, patients may pay $30 to $40 per month for insulin analogs vs $10 to $25 per month for cheaper versions of NPH.7,8
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Lipska KJ, Parker MM, Moffet HH, et al. Association of initiation of basal insulin analogs vs neutral protamine Hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320:53-62.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2017. www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed January 15, 2020.
3. Prentice JC, Conlin PR, Gellad WF, et al. Long-term outcomes of analogue insulin compared with NPH for patients with type 2 diabetes mellitus. Am J Manag Care. 2015;21:e235-e243.
4. Turner LW, Nartey D, Stafford RS, et al. Ambulatory treatment of type 2 diabetes in the U.S., 1997-2012. Diabetes Care. 2014;37:985-992.
5. Horvath K, Jeitler K, Berghold A, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(2):CD005613.
6. Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med. 2017;166:572-578.
7. GoodRx.com. Insulins. www.goodrx.com/insulins. Accessed January 20, 2020. 8. Cefalu WT, Dawes DE, Gavlak G, et al. Insulin access and affordability working group: conclusions and recommendations. Diabetes Care. 2018;41:1299-1311.
1. Lipska KJ, Parker MM, Moffet HH, et al. Association of initiation of basal insulin analogs vs neutral protamine Hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320:53-62.
2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2017. www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed January 15, 2020.
3. Prentice JC, Conlin PR, Gellad WF, et al. Long-term outcomes of analogue insulin compared with NPH for patients with type 2 diabetes mellitus. Am J Manag Care. 2015;21:e235-e243.
4. Turner LW, Nartey D, Stafford RS, et al. Ambulatory treatment of type 2 diabetes in the U.S., 1997-2012. Diabetes Care. 2014;37:985-992.
5. Horvath K, Jeitler K, Berghold A, et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(2):CD005613.
6. Chamberlain JJ, Herman WH, Leal S, et al. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association standards of medical care in diabetes. Ann Intern Med. 2017;166:572-578.
7. GoodRx.com. Insulins. www.goodrx.com/insulins. Accessed January 20, 2020. 8. Cefalu WT, Dawes DE, Gavlak G, et al. Insulin access and affordability working group: conclusions and recommendations. Diabetes Care. 2018;41:1299-1311.
PRACTICE CHANGER
Consider NPH insulin for patients who require initiation of long-acting insulin therapy because it is as safe as, and more cost-effective than, basal insulin analogs.
STRENGTH OF RECOMMENDATION
B: Based on a single, large, retrospective, observational study.
Lipska KJ, Parker MM, Moffet HH, et al. Association of initiation of basal insulin analogs vs neutral protamine Hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320:53-62.1
Supplemental oxygen: More isn’t always better
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 60-year-old woman who is generally healthy except for a history of recurrent urinary tract infections presents to the emergency department with fever, hypotension, and altered mental status, meeting criteria for septic shock. During her resuscitation, supplemental oxygen is administered. Standard treatment calls for a minimum SpO2 (saturation of peripheral oxygen) > 90%. What should your SpO2 goal be?
Use of supplemental oxygen in the acute care of the critically ill adult is a common practice in pre-hospital, emergency department (ED), and hospitalized settings.2,3 Despite their prevalence, guidelines about appropriate oxygen concentration and target SpO2 levels are often conflicting or vague.3-5
Excessive oxygen supplementation in acute illness may be harmful and cause increased risk of hypercapnic respiratory failure, delayed recognition of clinical deterioration, and oxygen toxicity.2,6 The perception of oxygen safety persists despite these findings, and it likely contributes to the ongoing practice of liberal oxygen supplementation in the acutely ill adult.2,7,8
STUDY SUMMARY
Liberal supplemental O2 linked to increased mortality
The Improving Oxygen Therapy in Acute illness (IOTA) study was a systematic review and meta-analysis of 25 randomized controlled trials (RCTs) that compared liberal vs conservative oxygen strategies for acutely ill adults (N = 16,037; median age = 64 years; range = 28-76 years). Patients with sepsis, critical illness, stroke, trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery were included. Studies were excluded if they involved patients who had chronic respiratory illness or psychiatric diseases, were receiving extracorporeal membrane oxygenation, were undergoing elective surgeries, were being treated with hyperbaric oxygen therapy, or were pregnant.
The outcomes studied were mortality (in-hospital, at 30 days, and at the longest follow-up) and morbidity (disability measured by the modified Rankin Scale at longest follow-up, risk of hospital-acquired pneumonia, risk of any hospital-acquired infection, and hospital length of stay).
Liberal supplemental oxygen, above an SpO2 range of 94% to 96%, increased mortality during inpatient stays (relative risk [RR] = 1.21; 95% confidence interval [CI], 1.03-1.43; N = 15,071), at 30 days (RR = 1.14; 95% CI, 1.01-1.29; N = 15,053), and at longest follow-up (RR = 1.10; 95% CI, 1.00-1.20; N = 15,754; median = 90 days; range = 14,365 days). There was no difference in morbidity outcomes between groups.
While it’s difficult to define a specific target SpO2 range, the number needed to harm when using a liberal oxygen approach (SpO2 > 96%) resulting in 1 death was 71 (95% CI, 37-1000).
Continue to: WHAT'S NEW
WHAT’S NEW
High-quality evidence points to the dangers of liberal O2 therapy
This comprehensive meta-analysis is the first high-quality evidence to suggest that liberal use of oxygen in acutely ill adults above a specific SpO2 level increases all-cause mortality. Previous small RCTs and observational studies have examined the effect of liberal oxygen only on specific presenting conditions, thus making more generalizable conclusions challenging.9-12
CAVEATS
Varied definitions of “liberal” and “conservative”
This review included studies with variable ranges of SpO2 defined as liberal vs conservative supplementation. However, in all of these, SpO2 above 96% was correlated with unfavorable outcomes.
The study excluded 2 potentially important patient groups: patients with chronic respiratory diseases and pregnant patients. Increased oxygen supplementation in patients with chronic respiratory diseases in noncritical settings has been shown to be deleterious.13-15 While this study does not address the issue of oxygen supplementation in acutely ill patients with chronic respiratory disease, use should be considered with caution. The results from this study may not be generalizable to women who are pregnant.
CHALLENGES TO IMPLEMENTATION
Reversing the tide
Liberal oxygen administration continues to be practiced in many health care settings. The main challenges to implementing the conclusions of this study are these pervasive practices.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
1. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
2. Hale KE, Gavin C, O’Driscoll BR. Audit of oxygen use in emergency ambulances and in a hospital emergency department. Emerg Med J. 2008;25:773-776.
3. O’Driscoll BR, Howard LS, Earis J, et al. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(suppl 1):ii1-ii90.
4. Kallstrom TJ, American Association for Respiratory Care. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility—2002 revision and update. Respir Care. 2002;47:717-720.
5. Henry TD, Torbati S. Oxygen for ACS: too much, too little, or just right? May 15, 2017. https://www.acc.org/latest-in-cardiology/articles/2017/05/15/08/34/oxygen-for-acs. Accessed October 1, 2019.
6. Hafner S, Beloncle F, Koch A, et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care. 2015;5:42.
7. Helmerhorst HJ, Schultz MJ, van der Voort PH, et al. Self-reported attitudes versus actual practice of oxygen therapy by ICU physicians and nurses. Ann Intensive Care. 2014;4:23.
8. Kelly CA, Lynes D, O’Brien MR, et al. A wolf in sheep’s clothing? Patients’ and healthcare professionals’ perceptions of oxygen therapy: an interpretative phenomenological analysis. Clin Respir J. 2018;12:616-632.
9. Meyhoff CS, Wetterslev J, Jorgensen LN, et al. Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial. JAMA. 2009;302:1543-1550.
10. Stub D, Smith K, Bernard S, et al. A randomized controlled trial on oxygen therapy in acute myocardial infarction Air Verses Oxygen in Myocardial infarction study (AVOID Study). Am Heart J. 2012;163:339-345.E1.
11. Girardis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316:1583-1589.
12. Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, et al. Association between arterial hyperoxia and outcome in subsets of critical illness: a systematic review, meta-analysis, and meta-regression of cohort studies. Crit Care Med. 2015;43:1508-1519.
13. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010;55:40-46.E1.
14. Kim V, Benditt JO, Wise RA, et al. Oxygen therapy in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:513-518.
15. Austin MA, Wills KE, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:C5462.
PRACTICE CHANGER
Do not use liberal oxygen therapy (SpO2 > 96%) in acutely ill adults, as it is associated with increased all-cause mortality.1
STRENGTH OF RECOMMENDATION
A: Based on a systematic review and meta-analysis of 25 randomized controlled trials.
Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-1705.
A Better Approach to the Diagnosis of PE
Penny E, a 48-year-old woman with a history of asthma, presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. PE is not your most likely diagnosis, but it is included in the differential, so you order a D
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2/1000 individuals and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
A diagnostic algorithm that includes the Wells criteria and a
Further, it is common for a
Three items of the original Wells criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 A total of 151 patients met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA). Investigators managed the remaining 3465 study patients according to the YEARS algorithm, which calls for obtaining a
PE was considered excluded if a patient had a
[polldaddy:10428150]
Continue to: Of the 1743 patients...
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%), with 6 patients (0.20%) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43%, which is similar to the 0.34% reported in a previous meta-analysis of the Wells rule algorithm.13 Overall, fatal PE occurred in 0.3% of patients in the YEARS cohort vs 0.6% in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells algorithm, for an absolute difference of 13% and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference) when compared with using the Wells rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria do not consider an age-adjusted
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[5]:286-287,295).
[embed:render:related:node:207775]
[embed:render:related:node:205882]
[embed:render:related:node:203909]
1. van der Hulle T, Cheung WY, Kooij S, et al; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(suppl 4):S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al; Prometheus Study Group. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and d -dimer testing to rule out pulmonary embolism: a systematic review and individual-patient data meta-analysis. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al; EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted d -dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including d -dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating d -dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal d -dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
Penny E, a 48-year-old woman with a history of asthma, presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. PE is not your most likely diagnosis, but it is included in the differential, so you order a D
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2/1000 individuals and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
A diagnostic algorithm that includes the Wells criteria and a
Further, it is common for a
Three items of the original Wells criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 A total of 151 patients met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA). Investigators managed the remaining 3465 study patients according to the YEARS algorithm, which calls for obtaining a
PE was considered excluded if a patient had a
[polldaddy:10428150]
Continue to: Of the 1743 patients...
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%), with 6 patients (0.20%) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43%, which is similar to the 0.34% reported in a previous meta-analysis of the Wells rule algorithm.13 Overall, fatal PE occurred in 0.3% of patients in the YEARS cohort vs 0.6% in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells algorithm, for an absolute difference of 13% and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference) when compared with using the Wells rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria do not consider an age-adjusted
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[5]:286-287,295).
[embed:render:related:node:207775]
[embed:render:related:node:205882]
[embed:render:related:node:203909]
Penny E, a 48-year-old woman with a history of asthma, presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. PE is not your most likely diagnosis, but it is included in the differential, so you order a D
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2/1000 individuals and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
A diagnostic algorithm that includes the Wells criteria and a
Further, it is common for a
Three items of the original Wells criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 A total of 151 patients met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA). Investigators managed the remaining 3465 study patients according to the YEARS algorithm, which calls for obtaining a
PE was considered excluded if a patient had a
[polldaddy:10428150]
Continue to: Of the 1743 patients...
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a D
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%), with 6 patients (0.20%) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43%, which is similar to the 0.34% reported in a previous meta-analysis of the Wells rule algorithm.13 Overall, fatal PE occurred in 0.3% of patients in the YEARS cohort vs 0.6% in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells algorithm, for an absolute difference of 13% and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference) when compared with using the Wells rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria do not consider an age-adjusted
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[5]:286-287,295).
[embed:render:related:node:207775]
[embed:render:related:node:205882]
[embed:render:related:node:203909]
1. van der Hulle T, Cheung WY, Kooij S, et al; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(suppl 4):S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al; Prometheus Study Group. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and d -dimer testing to rule out pulmonary embolism: a systematic review and individual-patient data meta-analysis. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al; EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted d -dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including d -dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating d -dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal d -dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
1. van der Hulle T, Cheung WY, Kooij S, et al; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(suppl 4):S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al; Prometheus Study Group. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and d -dimer testing to rule out pulmonary embolism: a systematic review and individual-patient data meta-analysis. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al; EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted d -dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including d -dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating d -dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal d -dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
Can Vitamin D Prevent Acute Respiratory Infections?
Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?
ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D is protective in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.
The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).
In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR, 0.98).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, a
In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).
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[embed:render:related:node:203909]
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1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. CDC National Center for Health Statistics. National Health Care Surveys. www.cdc.gov/nchs/dhcs.htm. Accessed September 5, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?
ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D is protective in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.
The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).
In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR, 0.98).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, a
In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).
[embed:render:related:node:205882]
[embed:render:related:node:203909]
[embed:render:related:node:202232]
Ms. M, a generally healthy 55-year-old woman, was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] level of 8 ng/mL). She presents with her second episode of acute viral bronchitis in the past 6 months. She has no history of significant smoking or exposure or history of asthma and does not take respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/wk in bolus dosing—but is that your best option for the patient?
ARTIs include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common reason for ambulatory care visits, accounting for almost 120 million (about 10% of all) visits per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D is protective in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N = 10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk for bias. The Cochrane risk-for-bias tool was used to address threats to validity.
The study included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI; and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR], 0.88; number needed to treat [NNT], 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR, 0.81), but bolus dosing (≥ 30,000 IU) was not (AOR, 0.97).
In 2-step analysis, patients benefited if they had baseline circulating 25(OH)D concentrations < 10 ng/mL (AOR, 0.30; NNT, 4); had baseline circulating 25(OH)D levels of 10 to 28 ng/mL (AOR, 0.75; NNT, 15); were ages 1.1 to 15.9 (AOR, 0.59); were ages 16 to 65 (AOR, 0.79); or had a BMI < 25 (AOR, 0.82).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25(OH)D ≥ 30 ng/mL did not appear to provide benefit (AOR, 0.96). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR, 0.98).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25(OH)D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect was noted in those who were most severely vitamin D deficient (those with circulating 25(OH)D levels < 10 ng/mL [NNT, 4] and those with circulating 25(OH)D levels 10-28 ng/mL [NNT, 15]). There was no demonstrable effect once circulating 25(OH)D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs. However, the doses studied were much lower than those commonly used (10,000 to 50,000 IU bolus), which were ineffective in reducing ARTIs in this meta-analysis. Changing from bolus dosing may prove challenging, a
In addition, the authors of the study suggest that one way to provide this level of vitamin D is through food fortification. But this method is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[4]:230-231).
[embed:render:related:node:205882]
[embed:render:related:node:203909]
[embed:render:related:node:202232]
1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. CDC National Center for Health Statistics. National Health Care Surveys. www.cdc.gov/nchs/dhcs.htm. Accessed September 5, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. CDC National Center for Health Statistics. National Health Care Surveys. www.cdc.gov/nchs/dhcs.htm. Accessed September 5, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blinded trial among young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
A better approach to the diagnosis of PE
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
PRACTICE CHANGER
Do not order computed tomography pulmonary angiography when evaluating patients for suspected pulmonary embolism unless: (1) the patient has a
STRENGTH OF RECOMMENDATION
A: Based on a prospective, multicenter, cohort study of 3616 patients with clinically suspected pulmonary embolism.1
van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
Can vitamin D prevent acute respiratory infections?
ILLUSTRATIVE CASE
Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?
Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D protects against ARTIs, but only in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.
The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or vitamin D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).
Continue to: In 2-step analysis...
In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or vitamin D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.
Continue to: In addition...
In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. Centers for Disease Control and Prevention. National Center for Health Statistics. National Health Care Surveys. http://www.cdc.gov/nchs/dhcs.htm. Accessed April 17, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blind trial in young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
ILLUSTRATIVE CASE
Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?
Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D protects against ARTIs, but only in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.
The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or vitamin D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).
Continue to: In 2-step analysis...
In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or vitamin D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.
Continue to: In addition...
In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?
Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.3 In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.2,4
While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.
STUDY SUMMARY
Vitamin D protects against ARTIs, but only in smaller doses
This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.
The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D3 or vitamin D2 supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.
Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).
Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).
Continue to: In 2-step analysis...
In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).
Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).
WHAT’S NEW
A more accurate snapshot
Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D3 or vitamin D2 that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.
CAVEATS
Only the most deficient benefit?
Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.
CHALLENGES TO IMPLEMENTATION
Breaking tradition
The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.
Continue to: In addition...
In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. Centers for Disease Control and Prevention. National Center for Health Statistics. National Health Care Surveys. http://www.cdc.gov/nchs/dhcs.htm. Accessed April 17, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blind trial in young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
2. Renati S, Linder JA. Necessity of office visits for acute respiratory infections in primary care. Fam Pract. 2016,33:312-317.
3. Centers for Disease Control and Prevention. National Center for Health Statistics. National Health Care Surveys. http://www.cdc.gov/nchs/dhcs.htm. Accessed April 17, 2019.
4. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-766.
5. Rees JR, Hendricks K, Barry EL, et al. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013;57:1384-1392.
6. Murdoch DR, Slow S, Chambers ST, et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012;308:1333-1339.
7. Laaksi I, Ruohola J-P, Mattila V, et al. Vitamin D supplementation for the prevention of acute respiratory tract infection: a randomized, double-blind trial in young Finnish men. Infect Dis. 2010;202:809-814.
8. Bergman P, Norlin A-C, Hansen S, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012;2:e001663.
PRACTICE CHANGER
Reduce acute respiratory tract infections in those with significant vitamin D deficiency (circulating 25-hydroxyvitamin D levels < 10 ng/mL) with daily or weekly vitamin D supplementation—not bolus vitamin D treatment.1
STRENGTH OF RECOMMENDATION
A: Based on a systematic review and meta-analysis of 25 trials.
Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.
First-time, Mild Diverticulitis: Antibiotics or Watchful Waiting?
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?
Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
Watchful waiting just as effective as antibiotics
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
Continue to: WHAT'S NEW
WHAT’S NEW
Study looked at true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize to worse cases
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
[embed:render:related:node:170847]
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).
[embed:render:related:node:194748]
[embed:render:related:node:175853]
[embed:render:related:node:173598]
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018;20(3):179-188.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?
Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
Watchful waiting just as effective as antibiotics
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
Continue to: WHAT'S NEW
WHAT’S NEW
Study looked at true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize to worse cases
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
[embed:render:related:node:170847]
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).
[embed:render:related:node:194748]
[embed:render:related:node:175853]
[embed:render:related:node:173598]
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?
Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
Watchful waiting just as effective as antibiotics
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
Continue to: WHAT'S NEW
WHAT’S NEW
Study looked at true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize to worse cases
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
[embed:render:related:node:170847]
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).
[embed:render:related:node:194748]
[embed:render:related:node:175853]
[embed:render:related:node:173598]
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018;20(3):179-188.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018;20(3):179-188.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
First-time, mild diverticulitis: Antibiotics or watchful waiting?
ILLUSTRATIVE CASE
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with over-the-counter medications. You suspect diverticulitis and obtain an abdominal computed tomography (CT) scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis.
How would you treat him?
Diverticulitis is common; about 200,000 people per year are admitted to the hospital because of diverticulitis in the United States.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized control trial (RCT; N=623) found that antibiotic treatment (compared with no antibiotic treatment) for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by a lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, non-uniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
RCT finds that watchful waiting is just as effective as antibiotic Tx
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adult patients in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomized to receive IV administration of amoxicillin-clavulanate 1200 mg 4 times daily for at least 48 hours followed by 625 mg PO 3 times daily for 10 total days of antibiotic treatment (n=266) or to be observed (n=262). Computerized randomization, with a random varying block size and stratified by Hinchey classification and center, was performed, and allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic treatment adverse effects; and all-cause mortality.
Continue to: Results
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 days vs 12 days; P=.15; hazard ratio [HR] for functional recovery=0.91; lower limit of 1-sided 95% confidence interval, 0.78). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up (complicated diverticulitis, 3.8% vs 2.6%, respectively; P=.377), recurrent diverticulitis (3.4% vs 3%; P=.494), readmission (17.6% vs 12%; P=.148), or adverse events (48.5% vs 54.5%; P=.221). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 days; P=.006). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
WHAT’S NEW
A study that looks at a true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate, or requirement for percutaneous drainage.7,8 This study is the first one to look at functional return to work (a true patient-oriented outcome). And it is the only study to look out to 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize findings to patients with worse forms of diverticulitis
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease), and is not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis maybe more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
Continuet to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018 Jan 11. doi: 10.1111/codi.14013.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
ILLUSTRATIVE CASE
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with over-the-counter medications. You suspect diverticulitis and obtain an abdominal computed tomography (CT) scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis.
How would you treat him?
Diverticulitis is common; about 200,000 people per year are admitted to the hospital because of diverticulitis in the United States.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized control trial (RCT; N=623) found that antibiotic treatment (compared with no antibiotic treatment) for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by a lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, non-uniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
RCT finds that watchful waiting is just as effective as antibiotic Tx
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adult patients in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomized to receive IV administration of amoxicillin-clavulanate 1200 mg 4 times daily for at least 48 hours followed by 625 mg PO 3 times daily for 10 total days of antibiotic treatment (n=266) or to be observed (n=262). Computerized randomization, with a random varying block size and stratified by Hinchey classification and center, was performed, and allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic treatment adverse effects; and all-cause mortality.
Continue to: Results
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 days vs 12 days; P=.15; hazard ratio [HR] for functional recovery=0.91; lower limit of 1-sided 95% confidence interval, 0.78). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up (complicated diverticulitis, 3.8% vs 2.6%, respectively; P=.377), recurrent diverticulitis (3.4% vs 3%; P=.494), readmission (17.6% vs 12%; P=.148), or adverse events (48.5% vs 54.5%; P=.221). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 days; P=.006). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
WHAT’S NEW
A study that looks at a true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate, or requirement for percutaneous drainage.7,8 This study is the first one to look at functional return to work (a true patient-oriented outcome). And it is the only study to look out to 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize findings to patients with worse forms of diverticulitis
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease), and is not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis maybe more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
Continuet to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with over-the-counter medications. You suspect diverticulitis and obtain an abdominal computed tomography (CT) scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis.
How would you treat him?
Diverticulitis is common; about 200,000 people per year are admitted to the hospital because of diverticulitis in the United States.2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.4
One previous randomized control trial (RCT; N=623) found that antibiotic treatment (compared with no antibiotic treatment) for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.5 The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by a lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, non-uniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.5
STUDY SUMMARY
RCT finds that watchful waiting is just as effective as antibiotic Tx
This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adult patients in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).1 (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.6) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.1
Observational vs antibiotic treatment. Enrolled patients were randomized to receive IV administration of amoxicillin-clavulanate 1200 mg 4 times daily for at least 48 hours followed by 625 mg PO 3 times daily for 10 total days of antibiotic treatment (n=266) or to be observed (n=262). Computerized randomization, with a random varying block size and stratified by Hinchey classification and center, was performed, and allocation was concealed. The investigators were masked to the allocation until all analyses were completed.1
The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic treatment adverse effects; and all-cause mortality.
Continue to: Results
Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 days vs 12 days; P=.15; hazard ratio [HR] for functional recovery=0.91; lower limit of 1-sided 95% confidence interval, 0.78). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up (complicated diverticulitis, 3.8% vs 2.6%, respectively; P=.377), recurrent diverticulitis (3.4% vs 3%; P=.494), readmission (17.6% vs 12%; P=.148), or adverse events (48.5% vs 54.5%; P=.221). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 days; P=.006). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.1
WHAT’S NEW
A study that looks at a true patient-oriented outcome
Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate, or requirement for percutaneous drainage.7,8 This study is the first one to look at functional return to work (a true patient-oriented outcome). And it is the only study to look out to 24 months to gauge long-term outcomes with observational treatment.
CAVEATS
Can’t generalize findings to patients with worse forms of diverticulitis
It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease), and is not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.
Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.1,9,10 This recommendation was based on an emerging understanding that diverticulitis maybe more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.9
Continuet to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to implementing this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018 Jan 11. doi: 10.1111/codi.14013.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
1. Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.
2. Wheat CL, Strate LL. Trends in hospitalization for diverticulitis and diverticular bleeding in the United States from 2000 to 2010. Clin Gastroenterol Hepatol. 2016;14:96-103.e1.
3. Matrana MR, Margolin DA. Epidemiology and pathophysiology of diverticular disease. Clin Colon Rectal Surg. 2009;22:141-146.
4. Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092.
5. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99:532-539.
6. Klarenbeek BR, de Korte N, van der Peet DL, et al. Review of current classifications for diverticular disease and a translation into clinical practice. Int J Colorectal Dis. 2012;27:207-214.
7. Tandon A, Fretwell VL, Nunes QM, et al. Antibiotics versus no antibiotics in the treatment of acute uncomplicated diverticulitis - a systematic review and meta-analysis. Colorectal Dis. 2018 Jan 11. doi: 10.1111/codi.14013.
8. Feingold D, Steele SR, Lee S, et al. Practice parameters for the treatment of sigmoid diverticulitis. Dis Colon Rectum. 2014;57:284-294.
9. Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149:1944-1949.
10. Sartelli M, Viale P, Catena F, et al. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013;8:3.
PRACTICE CHANGER
For mild, computed tomography-proven acute diverticulitis, consider observation only instead of antibiotic therapy.
STRENGTH OF RECOMMENDATION
B: Based on a single randomized controlled trial.
Daniels L, Ünlü Ç, de Korte N, et al, for the Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017;104:52-61.1
