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Systemic Racism and Health Disparities: A Statement from Editors of Family Medicine Journals
The year 2020 was marked by historic protests across the United States and the globe sparked by the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, and so many other Black people. The protests heightened awareness of racism as a public health crisis and triggered an antiracism movement. Racism is a pervasive and systemic issue that has profound adverse effects on health.1,2 Racism is associated with poorer mental and physical health outcomes and negative patient experiences in the health care system.3,4 As evidenced by the current coronavirus pandemic, race is a sociopolitical construct that continues to disadvantage Black, Latinx, Indigenous, and other People of Color.5,6,7,8 The association between racism and adverse health outcomes has been discussed for decades in the medical literature, including the family medicine literature. Today there is a renewed call to action for family medicine, a specialty that emerged as a counterculture to reform mainstream medicine,9 to both confront systemic racism and eliminate health disparities. This effort will require collaboration, commitment, education, and transformative conversations around racism, health inequity, and advocacy so that we can better serve our patients and our communities.
The editors of several North American family medicine publications have come together to address this call to action and share resources on racism across our readerships. We acknowledge those members of the family medicine scholar community who have been fighting for equity consistent with the Black Lives Matter movement by writing about racism, health inequities, and personal experiences of practicing as Black family physicians. While we recognize that much more work is needed, we want to amplify these voices. We have compiled a bibliography of scholarship generated by the family medicine community on the topic of racism in medicine.
The collection can be accessed here.
While this list is likely not complete, it does include over 250 published manuscripts and demonstrates expertise as well as a commitment to addressing these complex issues. For example, in 2016, Dr. J. Nwando Olayiwola, chair of the Department of Family Medicine at Ohio State University, wrote an essay on her experiences taking care of patients as a Black family physician.10 In January of 2019, Family Medicine published an entire issue devoted to racism in education and training.11 Dr. Eduardo Medina, a family physician and public health scholar, co-authored a call to action in 2016 for health professionals to dismantle structural racism and support Black lives to achieve health equity. His recent 2020 article builds on that theme and describes the disproportionate deaths of Black people due to racial injustice and the COVID-19 pandemic as converging public health emergencies.12,13 In the wake of these emergencies a fundamental transformation is warranted, and family physicians can play a key role.
We, the editors of family medicine journals, commit to actively examine the effects of racism on society and health and to take action to eliminate structural racism in our editorial processes. As an intellectual home for our profession, we have a unique responsibility and opportunity to educate and continue the conversation about institutional racism, health inequities, and antiracism in medicine. We will take immediate steps to enact tangible advances on these fronts. We will encourage and mentor authors from groups underrepresented in medicine. We will ensure that content includes an emphasis on cultural humility, diversity and inclusion, implicit bias, and the impact of racism on medicine and health. We will recruit editors and editorial board members from groups underrepresented in medicine. We will encourage collaboration and accountability within our specialty to confront systemic racism through content and processes in all of our individual publications. We recognize that these are small steps in an ongoing process of active antiracism, but we believe these steps are crucial. As editors in family medicine, we are committed to progress toward equity and justice.
Simultaneously published in American Family Physician, Annals of Family Medicine, Canadian Family Physician, Family Medicine, FP Essentials, FPIN/Evidence Based Practice, FPM, Journal of the American Board of Family Medicine, The Journal of Family Practice, and PRiMER.
Acknowledgement –
The authors thank Renee Crichlow, MD, Byron Jasper, MD, MPH, and Victoria Murrain, DO, for their insightful comments on this editorial.
1. Institute of Medicine (US) Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care, Smedley BD, Stith AY, Nelson AR, eds. Unequal treatment: confronting racial and ethnic disparities in health care. Washington, DC: National Academies Press; 2003.
2. Bailey ZD, Krieger N, Agénor M, Graves J, Linos N, Bassett MT. Structural racism and health inequities in the USA: evidence and interventions. Lancet. 2017;389(10077):1453-1463.
3. Ben J, Cormack D, Harris R, Paradies Y. Racism and health service utilisation: A systematic review and meta-analysis. PLoS One. 2017;12(12):e0189900.
4. Paradies Y, Ben J, Denson N, et al. Racism as a determinant of health: a systematic review and meta-analysis. PLoS One. 2015;10(9):e0138511.
5. American Academy of Family Physicians. Institutional racism in the health care system. Published 2019. Accessed Sept. 15, 2020. https://www.aafp.org/about/policies/all/institutional-racism.html.
6. Yaya S, Yeboah H, Charles CH, Otu A, Labonte R. Ethnic and racial disparities in COVID-19-related deaths: counting the trees, hiding the forest. BMJ Glob Health. 2020;5(6):e002913.
7. Egede LE, Walker RJ. Structural Racism, Social Risk Factors, and Covid-19 — A Dangerous Convergence for Black Americans [published online ahead of print, 2020 Jul 22]. N Engl J Med. 2020;10.1056/NEJMp2023616.
8. Centers for Disease Control and Prevention. Health equity considerations and racial and ethnic minority groups. Updated July 24, 2020. Accessed Sept. 15, 2020. https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/race-ethnicity.html
9. Stephens GG. Family medicine as counterculture. Fam Med. 1989;21(2):103-109.
10. Olayiwola JN. Racism in medicine: shifting the power. Ann Fam Med. 2016;14(3):267-269. https://doi.org/10.1370/afm.1932.
11. Saultz J, ed. Racism. Fam Med. 2019;51(1, theme issue):1-66.
12. Hardeman RR, Medina EM, Kozhimannil KB. Structural racism and supporting black lives - the role of health professionals. N Engl J Med. 2016;375(22):2113-2115. https://doi.org/10.1056/NEJMp1609535.
13. Hardeman RR, Medina EM, Boyd RW. Stolen breaths. N Engl J Med. 2020;383(3):197-199. 10.1056/NEJMp2021072.
The year 2020 was marked by historic protests across the United States and the globe sparked by the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, and so many other Black people. The protests heightened awareness of racism as a public health crisis and triggered an antiracism movement. Racism is a pervasive and systemic issue that has profound adverse effects on health.1,2 Racism is associated with poorer mental and physical health outcomes and negative patient experiences in the health care system.3,4 As evidenced by the current coronavirus pandemic, race is a sociopolitical construct that continues to disadvantage Black, Latinx, Indigenous, and other People of Color.5,6,7,8 The association between racism and adverse health outcomes has been discussed for decades in the medical literature, including the family medicine literature. Today there is a renewed call to action for family medicine, a specialty that emerged as a counterculture to reform mainstream medicine,9 to both confront systemic racism and eliminate health disparities. This effort will require collaboration, commitment, education, and transformative conversations around racism, health inequity, and advocacy so that we can better serve our patients and our communities.
The editors of several North American family medicine publications have come together to address this call to action and share resources on racism across our readerships. We acknowledge those members of the family medicine scholar community who have been fighting for equity consistent with the Black Lives Matter movement by writing about racism, health inequities, and personal experiences of practicing as Black family physicians. While we recognize that much more work is needed, we want to amplify these voices. We have compiled a bibliography of scholarship generated by the family medicine community on the topic of racism in medicine.
The collection can be accessed here.
While this list is likely not complete, it does include over 250 published manuscripts and demonstrates expertise as well as a commitment to addressing these complex issues. For example, in 2016, Dr. J. Nwando Olayiwola, chair of the Department of Family Medicine at Ohio State University, wrote an essay on her experiences taking care of patients as a Black family physician.10 In January of 2019, Family Medicine published an entire issue devoted to racism in education and training.11 Dr. Eduardo Medina, a family physician and public health scholar, co-authored a call to action in 2016 for health professionals to dismantle structural racism and support Black lives to achieve health equity. His recent 2020 article builds on that theme and describes the disproportionate deaths of Black people due to racial injustice and the COVID-19 pandemic as converging public health emergencies.12,13 In the wake of these emergencies a fundamental transformation is warranted, and family physicians can play a key role.
We, the editors of family medicine journals, commit to actively examine the effects of racism on society and health and to take action to eliminate structural racism in our editorial processes. As an intellectual home for our profession, we have a unique responsibility and opportunity to educate and continue the conversation about institutional racism, health inequities, and antiracism in medicine. We will take immediate steps to enact tangible advances on these fronts. We will encourage and mentor authors from groups underrepresented in medicine. We will ensure that content includes an emphasis on cultural humility, diversity and inclusion, implicit bias, and the impact of racism on medicine and health. We will recruit editors and editorial board members from groups underrepresented in medicine. We will encourage collaboration and accountability within our specialty to confront systemic racism through content and processes in all of our individual publications. We recognize that these are small steps in an ongoing process of active antiracism, but we believe these steps are crucial. As editors in family medicine, we are committed to progress toward equity and justice.
Simultaneously published in American Family Physician, Annals of Family Medicine, Canadian Family Physician, Family Medicine, FP Essentials, FPIN/Evidence Based Practice, FPM, Journal of the American Board of Family Medicine, The Journal of Family Practice, and PRiMER.
Acknowledgement –
The authors thank Renee Crichlow, MD, Byron Jasper, MD, MPH, and Victoria Murrain, DO, for their insightful comments on this editorial.
The year 2020 was marked by historic protests across the United States and the globe sparked by the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, and so many other Black people. The protests heightened awareness of racism as a public health crisis and triggered an antiracism movement. Racism is a pervasive and systemic issue that has profound adverse effects on health.1,2 Racism is associated with poorer mental and physical health outcomes and negative patient experiences in the health care system.3,4 As evidenced by the current coronavirus pandemic, race is a sociopolitical construct that continues to disadvantage Black, Latinx, Indigenous, and other People of Color.5,6,7,8 The association between racism and adverse health outcomes has been discussed for decades in the medical literature, including the family medicine literature. Today there is a renewed call to action for family medicine, a specialty that emerged as a counterculture to reform mainstream medicine,9 to both confront systemic racism and eliminate health disparities. This effort will require collaboration, commitment, education, and transformative conversations around racism, health inequity, and advocacy so that we can better serve our patients and our communities.
The editors of several North American family medicine publications have come together to address this call to action and share resources on racism across our readerships. We acknowledge those members of the family medicine scholar community who have been fighting for equity consistent with the Black Lives Matter movement by writing about racism, health inequities, and personal experiences of practicing as Black family physicians. While we recognize that much more work is needed, we want to amplify these voices. We have compiled a bibliography of scholarship generated by the family medicine community on the topic of racism in medicine.
The collection can be accessed here.
While this list is likely not complete, it does include over 250 published manuscripts and demonstrates expertise as well as a commitment to addressing these complex issues. For example, in 2016, Dr. J. Nwando Olayiwola, chair of the Department of Family Medicine at Ohio State University, wrote an essay on her experiences taking care of patients as a Black family physician.10 In January of 2019, Family Medicine published an entire issue devoted to racism in education and training.11 Dr. Eduardo Medina, a family physician and public health scholar, co-authored a call to action in 2016 for health professionals to dismantle structural racism and support Black lives to achieve health equity. His recent 2020 article builds on that theme and describes the disproportionate deaths of Black people due to racial injustice and the COVID-19 pandemic as converging public health emergencies.12,13 In the wake of these emergencies a fundamental transformation is warranted, and family physicians can play a key role.
We, the editors of family medicine journals, commit to actively examine the effects of racism on society and health and to take action to eliminate structural racism in our editorial processes. As an intellectual home for our profession, we have a unique responsibility and opportunity to educate and continue the conversation about institutional racism, health inequities, and antiracism in medicine. We will take immediate steps to enact tangible advances on these fronts. We will encourage and mentor authors from groups underrepresented in medicine. We will ensure that content includes an emphasis on cultural humility, diversity and inclusion, implicit bias, and the impact of racism on medicine and health. We will recruit editors and editorial board members from groups underrepresented in medicine. We will encourage collaboration and accountability within our specialty to confront systemic racism through content and processes in all of our individual publications. We recognize that these are small steps in an ongoing process of active antiracism, but we believe these steps are crucial. As editors in family medicine, we are committed to progress toward equity and justice.
Simultaneously published in American Family Physician, Annals of Family Medicine, Canadian Family Physician, Family Medicine, FP Essentials, FPIN/Evidence Based Practice, FPM, Journal of the American Board of Family Medicine, The Journal of Family Practice, and PRiMER.
Acknowledgement –
The authors thank Renee Crichlow, MD, Byron Jasper, MD, MPH, and Victoria Murrain, DO, for their insightful comments on this editorial.
1. Institute of Medicine (US) Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care, Smedley BD, Stith AY, Nelson AR, eds. Unequal treatment: confronting racial and ethnic disparities in health care. Washington, DC: National Academies Press; 2003.
2. Bailey ZD, Krieger N, Agénor M, Graves J, Linos N, Bassett MT. Structural racism and health inequities in the USA: evidence and interventions. Lancet. 2017;389(10077):1453-1463.
3. Ben J, Cormack D, Harris R, Paradies Y. Racism and health service utilisation: A systematic review and meta-analysis. PLoS One. 2017;12(12):e0189900.
4. Paradies Y, Ben J, Denson N, et al. Racism as a determinant of health: a systematic review and meta-analysis. PLoS One. 2015;10(9):e0138511.
5. American Academy of Family Physicians. Institutional racism in the health care system. Published 2019. Accessed Sept. 15, 2020. https://www.aafp.org/about/policies/all/institutional-racism.html.
6. Yaya S, Yeboah H, Charles CH, Otu A, Labonte R. Ethnic and racial disparities in COVID-19-related deaths: counting the trees, hiding the forest. BMJ Glob Health. 2020;5(6):e002913.
7. Egede LE, Walker RJ. Structural Racism, Social Risk Factors, and Covid-19 — A Dangerous Convergence for Black Americans [published online ahead of print, 2020 Jul 22]. N Engl J Med. 2020;10.1056/NEJMp2023616.
8. Centers for Disease Control and Prevention. Health equity considerations and racial and ethnic minority groups. Updated July 24, 2020. Accessed Sept. 15, 2020. https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/race-ethnicity.html
9. Stephens GG. Family medicine as counterculture. Fam Med. 1989;21(2):103-109.
10. Olayiwola JN. Racism in medicine: shifting the power. Ann Fam Med. 2016;14(3):267-269. https://doi.org/10.1370/afm.1932.
11. Saultz J, ed. Racism. Fam Med. 2019;51(1, theme issue):1-66.
12. Hardeman RR, Medina EM, Kozhimannil KB. Structural racism and supporting black lives - the role of health professionals. N Engl J Med. 2016;375(22):2113-2115. https://doi.org/10.1056/NEJMp1609535.
13. Hardeman RR, Medina EM, Boyd RW. Stolen breaths. N Engl J Med. 2020;383(3):197-199. 10.1056/NEJMp2021072.
1. Institute of Medicine (US) Committee on Understanding and Eliminating Racial and Ethnic Disparities in Health Care, Smedley BD, Stith AY, Nelson AR, eds. Unequal treatment: confronting racial and ethnic disparities in health care. Washington, DC: National Academies Press; 2003.
2. Bailey ZD, Krieger N, Agénor M, Graves J, Linos N, Bassett MT. Structural racism and health inequities in the USA: evidence and interventions. Lancet. 2017;389(10077):1453-1463.
3. Ben J, Cormack D, Harris R, Paradies Y. Racism and health service utilisation: A systematic review and meta-analysis. PLoS One. 2017;12(12):e0189900.
4. Paradies Y, Ben J, Denson N, et al. Racism as a determinant of health: a systematic review and meta-analysis. PLoS One. 2015;10(9):e0138511.
5. American Academy of Family Physicians. Institutional racism in the health care system. Published 2019. Accessed Sept. 15, 2020. https://www.aafp.org/about/policies/all/institutional-racism.html.
6. Yaya S, Yeboah H, Charles CH, Otu A, Labonte R. Ethnic and racial disparities in COVID-19-related deaths: counting the trees, hiding the forest. BMJ Glob Health. 2020;5(6):e002913.
7. Egede LE, Walker RJ. Structural Racism, Social Risk Factors, and Covid-19 — A Dangerous Convergence for Black Americans [published online ahead of print, 2020 Jul 22]. N Engl J Med. 2020;10.1056/NEJMp2023616.
8. Centers for Disease Control and Prevention. Health equity considerations and racial and ethnic minority groups. Updated July 24, 2020. Accessed Sept. 15, 2020. https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/race-ethnicity.html
9. Stephens GG. Family medicine as counterculture. Fam Med. 1989;21(2):103-109.
10. Olayiwola JN. Racism in medicine: shifting the power. Ann Fam Med. 2016;14(3):267-269. https://doi.org/10.1370/afm.1932.
11. Saultz J, ed. Racism. Fam Med. 2019;51(1, theme issue):1-66.
12. Hardeman RR, Medina EM, Kozhimannil KB. Structural racism and supporting black lives - the role of health professionals. N Engl J Med. 2016;375(22):2113-2115. https://doi.org/10.1056/NEJMp1609535.
13. Hardeman RR, Medina EM, Boyd RW. Stolen breaths. N Engl J Med. 2020;383(3):197-199. 10.1056/NEJMp2021072.
Does hypercoagulopathy testing benefit patients with DVT?
NO. There is no evidence to suggest that testing for hypercoagulopathy benefits most patients with deep venous thrombosis (DVT). Nor has research established that thrombophilia test results improve the ability to predict recurrence better than clinical risk assessment alone (strength of recommendation [SOR]: B, multiple cohort studies).
Testing may be warranted in patients younger than 50 years with idiopathic DVT or patients with recurrent episodes of thromboembolism to assess risk in other family members (SOR: C, expert opinion).
A theoretical cost-benefit analysis demonstrates that testing for antiphospholipid antibody syndrome and homozygous factor V Leiden may be cost effective when comparing quality-adjusted life years in patients with idiopathic DVT (SOR: B, single cost-benefit analysis).
Evidence summary
For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.
Testing doesn’t predict risk more accurately than clinical history
Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.5-7
TABLE
Thrombophilic conditions that increase the risk of DVT
| Thrombophilic condition | Prevalence in patients with first DVT1 | Relative risk of DVT compared with noncarriers1-3 |
|---|---|---|
| Antithrombin deficiency | 1% | 5 |
| Protein C | 3% | 3.1-3.4 |
| Protein S | 1%-2% | 2 |
| Factor V Leiden | 20% | 1.14-2.12 (heterozygous) 1.2-6.0 (homozygous) |
| Prothrombin G20210A | 6% | 1.9-2.8 |
| Elevated anticardiolipin antibodies | 14% | 1.6-3.2 |
| Lupus anticoagulant | 5%-15% | 9-11 |
| Hyperhomocystinemia | 10%-25% | 2.7 |
| DVT, deep vein thrombosis. | ||
Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.8 Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.
Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.4 After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.
A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.9 Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.
Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.8
Recommendations
A consensus opinion from the British Society for Haematology concludes that:
- thrombophilia testing of unselected patients is inappropriate
- initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
- identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.10
The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.
1. Deitcher SR, Gomes MP. Hypercoagulable state testing and malignancy screening following venous thromboembolic events. Vasc Med. 2003;8:33-46.
2. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44:62-69.
3. Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301:2472-2485.
4. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
5. Baglin T, Luddington R, Brown K, et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523-526.
6. Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med. 2002;162:2357-2360.
7. Laczkovics C, Grafenhofer H, Kaider A, et al. Risk of recurrence after a first venous thromboembolic event in young women. Haematologica. 2007;92:1201-1207.
8. Auerbach AD, Sanders GD, Hambleton J. Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis. Am J Med. 2004;116:816-828.
9. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev. 2006;(1):CD001367.-
10. Haemostasis and Thrombosis Task Force. British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol. 2001;114:512-528.
NO. There is no evidence to suggest that testing for hypercoagulopathy benefits most patients with deep venous thrombosis (DVT). Nor has research established that thrombophilia test results improve the ability to predict recurrence better than clinical risk assessment alone (strength of recommendation [SOR]: B, multiple cohort studies).
Testing may be warranted in patients younger than 50 years with idiopathic DVT or patients with recurrent episodes of thromboembolism to assess risk in other family members (SOR: C, expert opinion).
A theoretical cost-benefit analysis demonstrates that testing for antiphospholipid antibody syndrome and homozygous factor V Leiden may be cost effective when comparing quality-adjusted life years in patients with idiopathic DVT (SOR: B, single cost-benefit analysis).
Evidence summary
For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.
Testing doesn’t predict risk more accurately than clinical history
Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.5-7
TABLE
Thrombophilic conditions that increase the risk of DVT
| Thrombophilic condition | Prevalence in patients with first DVT1 | Relative risk of DVT compared with noncarriers1-3 |
|---|---|---|
| Antithrombin deficiency | 1% | 5 |
| Protein C | 3% | 3.1-3.4 |
| Protein S | 1%-2% | 2 |
| Factor V Leiden | 20% | 1.14-2.12 (heterozygous) 1.2-6.0 (homozygous) |
| Prothrombin G20210A | 6% | 1.9-2.8 |
| Elevated anticardiolipin antibodies | 14% | 1.6-3.2 |
| Lupus anticoagulant | 5%-15% | 9-11 |
| Hyperhomocystinemia | 10%-25% | 2.7 |
| DVT, deep vein thrombosis. | ||
Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.8 Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.
Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.4 After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.
A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.9 Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.
Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.8
Recommendations
A consensus opinion from the British Society for Haematology concludes that:
- thrombophilia testing of unselected patients is inappropriate
- initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
- identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.10
The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.
NO. There is no evidence to suggest that testing for hypercoagulopathy benefits most patients with deep venous thrombosis (DVT). Nor has research established that thrombophilia test results improve the ability to predict recurrence better than clinical risk assessment alone (strength of recommendation [SOR]: B, multiple cohort studies).
Testing may be warranted in patients younger than 50 years with idiopathic DVT or patients with recurrent episodes of thromboembolism to assess risk in other family members (SOR: C, expert opinion).
A theoretical cost-benefit analysis demonstrates that testing for antiphospholipid antibody syndrome and homozygous factor V Leiden may be cost effective when comparing quality-adjusted life years in patients with idiopathic DVT (SOR: B, single cost-benefit analysis).
Evidence summary
For thrombophilia testing to be of clinical value in patients with DVT, it must be superior to clinical history alone in determining who is at risk for recurrence; changing therapy based on a positive test must improve clinical outcomes.
Testing doesn’t predict risk more accurately than clinical history
Several thombophilic conditions are associated with increased risk for both first and recurrent DVT (TABLE).1-3 Certain clinical characteristics also markedly increase the risk of recurrence, including breast cancer (when the patient is on chemotherapy), lung, pancreatic and other gastrointestinal cancers, some major surgeries, and a history of previous DVT.1-4 Three cohort studies show that thrombophilia test results don’t assess recurrence risk more accurately than these historical factors alone for most patients.5-7
TABLE
Thrombophilic conditions that increase the risk of DVT
| Thrombophilic condition | Prevalence in patients with first DVT1 | Relative risk of DVT compared with noncarriers1-3 |
|---|---|---|
| Antithrombin deficiency | 1% | 5 |
| Protein C | 3% | 3.1-3.4 |
| Protein S | 1%-2% | 2 |
| Factor V Leiden | 20% | 1.14-2.12 (heterozygous) 1.2-6.0 (homozygous) |
| Prothrombin G20210A | 6% | 1.9-2.8 |
| Elevated anticardiolipin antibodies | 14% | 1.6-3.2 |
| Lupus anticoagulant | 5%-15% | 9-11 |
| Hyperhomocystinemia | 10%-25% | 2.7 |
| DVT, deep vein thrombosis. | ||
Testing may be cost effective for patients with idiopathic DVT
Auerbach and colleagues developed a mathematical model of cost effectiveness and concluded that thrombophilia testing may be cost effective for patients with idiopathic DVT.8 Their analysis was based on theoretical assumptions that might oversimplify the complexities of practice, however. No clinical trials compare different treatment regimens based on the results of thrombophilia tests.
Prolonged anticoagulation may benefit high-risk patients
Few studies have compared various durations of warfarin treatment for patients with DVT. The risk of recurrence is highest in the first 6 to 12 months after an initial episode.4 After 12 months the risk decreases, but never to the risk level of people who have never had a DVT.
A Cochrane meta-analysis of 8 RCTs, totaling 2994 patients, evaluated duration of treatment with vitamin K antagonists in DVT. It concluded that although prolonged treatment with vitamin K antagonists reduces the risk of DVT, substantial ongoing risk of bleeding complications remains.9 Prolonged or even lifelong treatment may be considered for high-risk patients with multiple episodes of DVT or pulmonary embolism.
Cost-effectiveness analysis suggests that prolonged warfarin therapy for patients with the highest risk thrombophilic conditions (homozygous factor V Leiden and antiphospholipid antibody syndrome) also may be warranted.8
Recommendations
A consensus opinion from the British Society for Haematology concludes that:
- thrombophilia testing of unselected patients is inappropriate
- initial management of DVT or pulmonary embolism in patients with heritable thrombophilia is no different from that in other patients
- identification of the most prevalent forms of heritable thrombophilia, heterozygous factor V Leiden or prothrombin G20210A, shouldn’t influence decisions about duration of anticoagulation therapy.10
The consensus statement suggests indefinite anticoagulation for patients with 2 or more spontaneous venous thrombotic events.
1. Deitcher SR, Gomes MP. Hypercoagulable state testing and malignancy screening following venous thromboembolic events. Vasc Med. 2003;8:33-46.
2. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44:62-69.
3. Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301:2472-2485.
4. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
5. Baglin T, Luddington R, Brown K, et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523-526.
6. Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med. 2002;162:2357-2360.
7. Laczkovics C, Grafenhofer H, Kaider A, et al. Risk of recurrence after a first venous thromboembolic event in young women. Haematologica. 2007;92:1201-1207.
8. Auerbach AD, Sanders GD, Hambleton J. Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis. Am J Med. 2004;116:816-828.
9. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev. 2006;(1):CD001367.-
10. Haemostasis and Thrombosis Task Force. British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol. 2001;114:512-528.
1. Deitcher SR, Gomes MP. Hypercoagulable state testing and malignancy screening following venous thromboembolic events. Vasc Med. 2003;8:33-46.
2. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44:62-69.
3. Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301:2472-2485.
4. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
5. Baglin T, Luddington R, Brown K, et al. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523-526.
6. Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med. 2002;162:2357-2360.
7. Laczkovics C, Grafenhofer H, Kaider A, et al. Risk of recurrence after a first venous thromboembolic event in young women. Haematologica. 2007;92:1201-1207.
8. Auerbach AD, Sanders GD, Hambleton J. Cost-effectiveness of testing for hypercoagulability and effects on treatment strategies in patients with deep vein thrombosis. Am J Med. 2004;116:816-828.
9. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev. 2006;(1):CD001367.-
10. Haemostasis and Thrombosis Task Force. British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol. 2001;114:512-528.
Evidence-based answers from the Family Physicians Inquiries Network
What GI stress ulcer prophylaxis should we provide hospitalized patients?
Patients in intensive care unit (ICE) settings who are receiving prolonged mechanical ventilation (for >48 hours) or who have a coagulopathy or multiple organ dysfunction (especially renal failure) should receive stress ulcer prophylaxis. Current evidence does not support prophylaxis for non-ICU patients1,2 (strength of recommendation [SOR]: B, based on multiple systematic reviews).
Prophylaxis with H2 receptor antagonists (H2RAs) and sucralfate are equally efficacious in lowering mortality and length of hospital stay.3 No randomized controlled trials demonstrate that proton pump inhibitors (PPIs) are superior to H2RAs or sucralfate (SOR: B, based on multiple systematic reviews.)
Consider a protocol to identify patients needing prophylaxis in the ICU
Julia Fashner, MD
Wright State University Boonshoft School of Medicine, Detroit, Mich
Many patients may enter the hospital already on a PPI for reflux disease or prevention of gastrointestinal side effects from other medications. This Clinical Inquiry shows that only certain patients in the hospital will benefit from prophylaxis for stress ulcers and have less bleeding. Therefore, consider using a protocol to identify those specific patients in the ICU and place them on an H2 blocker, PPI or sucralfate automatically.
Evidence summary
Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.4 Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.5 Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).1
Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.
Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).6 In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.
Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.3 Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.
TABLE
Risk factors for stress ulcers
| STRESS ULCER RISK FACTORS | ODDS RATIOS FOR CLINICALLY IMPORTANT BLEEDING (95% CI) |
|---|---|
| Mechanical ventilation >48 hours5 | 3.4 (1.0–11) |
| Platelet count <50,0001,2 | 2.58 (1.19–5.57) |
| Maximum serum creatinine1 | 1.16 (1.02–1.32) |
Recommendation from others
In the American Journal of Health-System Pharmacy, Allen et al5 state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report7 states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”
1. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999;27:2812-2817.
2. Cook DJ, Reeve BK, Scholes LC. Histamine-2-receptor antagonists and antacids in the critically ill population: stress ulceration versus nosocomial pneumonia. Infect Control Hosp Epidemiol 1994;15:437-442.
3. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338:791-797.
4. Zinner MJ, Rypins EB, Martin LR, et al. Misoprostel versus antacid titration for preventing stress Ulcers in postoperative surgical ICU patients. Ann Surg 1989;210:590-595.
5. Allen ME, Kopp BJ, Erstad BL. Stress ulcer prophylaxis in the postoperative period. Am J Health Syst Pharm 2004;61:588-596.
6. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308-314.
7. Making health care safer: a critical analysis of patient safety practices. Evidence report/technology assessment #43. Contract no. 290-97-0013, Chapter 43, AHRQ 2001, Rockville, Md.
Patients in intensive care unit (ICE) settings who are receiving prolonged mechanical ventilation (for >48 hours) or who have a coagulopathy or multiple organ dysfunction (especially renal failure) should receive stress ulcer prophylaxis. Current evidence does not support prophylaxis for non-ICU patients1,2 (strength of recommendation [SOR]: B, based on multiple systematic reviews).
Prophylaxis with H2 receptor antagonists (H2RAs) and sucralfate are equally efficacious in lowering mortality and length of hospital stay.3 No randomized controlled trials demonstrate that proton pump inhibitors (PPIs) are superior to H2RAs or sucralfate (SOR: B, based on multiple systematic reviews.)
Consider a protocol to identify patients needing prophylaxis in the ICU
Julia Fashner, MD
Wright State University Boonshoft School of Medicine, Detroit, Mich
Many patients may enter the hospital already on a PPI for reflux disease or prevention of gastrointestinal side effects from other medications. This Clinical Inquiry shows that only certain patients in the hospital will benefit from prophylaxis for stress ulcers and have less bleeding. Therefore, consider using a protocol to identify those specific patients in the ICU and place them on an H2 blocker, PPI or sucralfate automatically.
Evidence summary
Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.4 Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.5 Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).1
Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.
Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).6 In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.
Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.3 Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.
TABLE
Risk factors for stress ulcers
| STRESS ULCER RISK FACTORS | ODDS RATIOS FOR CLINICALLY IMPORTANT BLEEDING (95% CI) |
|---|---|
| Mechanical ventilation >48 hours5 | 3.4 (1.0–11) |
| Platelet count <50,0001,2 | 2.58 (1.19–5.57) |
| Maximum serum creatinine1 | 1.16 (1.02–1.32) |
Recommendation from others
In the American Journal of Health-System Pharmacy, Allen et al5 state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report7 states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”
Patients in intensive care unit (ICE) settings who are receiving prolonged mechanical ventilation (for >48 hours) or who have a coagulopathy or multiple organ dysfunction (especially renal failure) should receive stress ulcer prophylaxis. Current evidence does not support prophylaxis for non-ICU patients1,2 (strength of recommendation [SOR]: B, based on multiple systematic reviews).
Prophylaxis with H2 receptor antagonists (H2RAs) and sucralfate are equally efficacious in lowering mortality and length of hospital stay.3 No randomized controlled trials demonstrate that proton pump inhibitors (PPIs) are superior to H2RAs or sucralfate (SOR: B, based on multiple systematic reviews.)
Consider a protocol to identify patients needing prophylaxis in the ICU
Julia Fashner, MD
Wright State University Boonshoft School of Medicine, Detroit, Mich
Many patients may enter the hospital already on a PPI for reflux disease or prevention of gastrointestinal side effects from other medications. This Clinical Inquiry shows that only certain patients in the hospital will benefit from prophylaxis for stress ulcers and have less bleeding. Therefore, consider using a protocol to identify those specific patients in the ICU and place them on an H2 blocker, PPI or sucralfate automatically.
Evidence summary
Critically ill patients are at increased risk of bleeding from stress-induced gastroduodenal ulceration. Decades ago, ICUs began using pharmacologic prophylaxis on most patients to prevent gastrointestinal bleeding, which had a mortality rate as high as 80%. Before the advent of prophylaxis, the incidence of upper gastro-intestinal bleeding was 6% to 25%.4 Since then, improvements in ICU management have decreased this incidence to 0% to 2.8%.5 Recent studies suggest that only ICU patients with certain risk factors benefit from ulcer prophylaxis (TABLE).1
Our search retrieved 20 randomized controlled trials and 6 systematic reviews with meta-analyses from the Medline database since 1990. It was difficult to find a consensus on the matter of stress ulcer prophylaxis because of inconsistencies in the outcomes measured in these studies. We focused on studies examining clinically important bleeding, but even in these studies definitions and measurements vary. Few studies addressed mortality or length of stay; those that did reported no significant difference in either outcome with prophylaxis.
Medications used to prevent gastrointestinal bleeding have included antacids, sucralfate, H2RAs, and PPIs. Sucralfate and H2RAs have been studied most frequently, and both agents significantly reduce the incidence of clinically important bleeding in high-risk patients. Compared with placebo, the odds ratio for clinically important bleeding was 0.44 with ranitidine (95% confidence interval [CI], 0.22–0.88) and 0.58 with sucralfate (95% CI, 0.34–0.99).6 In a population with a clinically important bleeding incidence of 3% to 6%, a range consistent with the most recent studies we reviewed, the number needed to treat to prevent 1 bleeding episode is 30 to 60 for ranitidine and 40 to 79 for sucralfate.
Some studies suggest that pharmacologic prophylaxis may increase the incidence of aspiration pneumonia in ventilator-dependent patients. The largest randomized trial addressing this issue (N=1200) found no significant difference between H2RAs and sucralfate in ventilator-associated pneumonia.3 Improved ICU management, such as frequent suctioning, upright positioning, and use of enteral nutrition may help prevent nosocomial pneumonia due to aspiration.
TABLE
Risk factors for stress ulcers
| STRESS ULCER RISK FACTORS | ODDS RATIOS FOR CLINICALLY IMPORTANT BLEEDING (95% CI) |
|---|---|
| Mechanical ventilation >48 hours5 | 3.4 (1.0–11) |
| Platelet count <50,0001,2 | 2.58 (1.19–5.57) |
| Maximum serum creatinine1 | 1.16 (1.02–1.32) |
Recommendation from others
In the American Journal of Health-System Pharmacy, Allen et al5 state “the frequency of clinically important bleeding is low … the majority of recently published prospective studies and meta-analyses have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents.” A 2001 Agency for Healthcare Research and Quality evidence report7 states that the evidence is not conclusive that all intensive care patients benefit from stress ulcer prophylaxis and that clinicians “may consider use of prophylactic agents in very high risk patients.”
1. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999;27:2812-2817.
2. Cook DJ, Reeve BK, Scholes LC. Histamine-2-receptor antagonists and antacids in the critically ill population: stress ulceration versus nosocomial pneumonia. Infect Control Hosp Epidemiol 1994;15:437-442.
3. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338:791-797.
4. Zinner MJ, Rypins EB, Martin LR, et al. Misoprostel versus antacid titration for preventing stress Ulcers in postoperative surgical ICU patients. Ann Surg 1989;210:590-595.
5. Allen ME, Kopp BJ, Erstad BL. Stress ulcer prophylaxis in the postoperative period. Am J Health Syst Pharm 2004;61:588-596.
6. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308-314.
7. Making health care safer: a critical analysis of patient safety practices. Evidence report/technology assessment #43. Contract no. 290-97-0013, Chapter 43, AHRQ 2001, Rockville, Md.
1. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999;27:2812-2817.
2. Cook DJ, Reeve BK, Scholes LC. Histamine-2-receptor antagonists and antacids in the critically ill population: stress ulceration versus nosocomial pneumonia. Infect Control Hosp Epidemiol 1994;15:437-442.
3. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338:791-797.
4. Zinner MJ, Rypins EB, Martin LR, et al. Misoprostel versus antacid titration for preventing stress Ulcers in postoperative surgical ICU patients. Ann Surg 1989;210:590-595.
5. Allen ME, Kopp BJ, Erstad BL. Stress ulcer prophylaxis in the postoperative period. Am J Health Syst Pharm 2004;61:588-596.
6. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308-314.
7. Making health care safer: a critical analysis of patient safety practices. Evidence report/technology assessment #43. Contract no. 290-97-0013, Chapter 43, AHRQ 2001, Rockville, Md.
Evidence-based answers from the Family Physicians Inquiries Network