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Four-week, 8-week CAB/RPV injections safe, effective in women
according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.
Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.
Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.
Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.
At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.
Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.
There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.
Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.
Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
This article first appeared on Medscape.com.
according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.
Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.
Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.
Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.
At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.
Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.
There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.
Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.
Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
This article first appeared on Medscape.com.
according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.
Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.
Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.
Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.
At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.
Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.
There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.
Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.
Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
This article first appeared on Medscape.com.
Social factors predicted peripartum depressive symptoms in Black women with HIV
Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.
Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.
In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.
Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
Social factors show significant impact
In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.
The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.
The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
Quantitative studies needed
Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.
The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.
“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.
Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.
Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.
In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.
Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
Social factors show significant impact
In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.
The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.
The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
Quantitative studies needed
Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.
The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.
“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.
Women with high-risk pregnancies because of chronic conditions are at increased risk for developing postpartum depression, and HIV may be one such risk. However, risk factors for women living with HIV, particularly Black women, have not been well studied, wrote Emmanuela Nneamaka Ojukwu of the University of Miami School of Nursing, and colleagues.
Data suggest that as many as half of cases of postpartum depression (PPD) begin before delivery, the researchers noted. “Therefore, for this study, the symptoms of both PND (prenatal depression) and PPD have been classified in what we have termed peripartum depressive symptoms (PDS),” and defined as depressive symptoms during pregnancy and within 1 year postpartum, they said.
In a study published in the Archives of Psychiatric Nursing, the researchers conducted a secondary analysis of 143 Black women living with HIV seen at specialty prenatal and women’s health clinics in Miami.
Overall, 81 women (57%) reported either perinatal or postpartum depressive symptoms, or both. “Some of the symptoms prevalent among women in our study included restlessness, depressed mood, apathy, guilt, hopelessness, and social isolation,” the researchers said.
Social factors show significant impact
In a multivariate analysis, low income, intimate partner violence, and childcare burden were significant predictors of PDS (P less than .05). Women who reported intimate partner violence or abuse were 6.5 times more likely to experience PDS than were women who did not report abuse, and women with a childcare burden involving two children were 4.6 times more likely to experience PDS than were women with no childcare burden or only one child needing child care.
The average age of the women studied was 29 years, and 59% were above the federal poverty level. Nearly two-thirds (62%) were Black and 38% were Haitian; 63% were unemployed, 62% had a high school diploma or less, and 59% received care through Medicaid.
The researchers assessed four categories of health: HIV-related, gynecologic, obstetric, and psychosocial. The average viral load among the patients was 22,359 copies/mL at baseline, and they averaged 2.5 medical comorbidities. The most common comorbid conditions were other sexually transmitted infections and blood disorders, followed by cardiovascular and metabolic conditions.
Quantitative studies needed
Larger quantitative studies of Black pregnant women living with HIV are needed to analyze social factors at multiple levels, the researchers said. “To address depression among Black women living with HIV, local and federal governments should enact measures that increase the family income and diminish the prevalence of [intimate partner violence] among these women,” they said.
The study findings were limited by several factors including retrospective design and use of self-reports, as well as the small sample size and lack of generalizability to women living with HIV of other races or from other regions, the researchers noted. However, the results reflect data from previous studies and support the value of early screening and referral to improve well being for Black women living with HIV, as well as the importance of comprehensive medical care, they said.
“Women should be counseled that postpartum physical and psychological changes (and the stresses and demands of caring for a new baby) may make [antiretroviral] adherence more difficult and that additional support may be needed during this period,” the researchers wrote.
The study received no outside funding. The researchers had no financial conflicts to disclose.
SOURCE: Ojukwu EN et al. Arch Psychiatr Nurs. 2020 May 22. doi: 10.1016/j.apnu.2020.05.004.
FROM ARCHIVES OF PSYCHIATRIC NURSING
Choose wisely
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
Editor-in-Chief
Editor-in-Chief
Editor-in-Chief
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
Four years ago, just prior to the 2016 presidential election, I mentioned the Choosing Wisely campaign in my JFP editorial.1 I said that family physicians should do their part in controlling health care costs by carefully selecting tests and treatments that are known to be effective and avoiding those that are not. This remains as true now as it was then.
The Choosing Wisely campaign was sparked by a family physician, Dr. Howard Brody, in the context of national health care reform. In a 2010 New England Journal of Medicine editorial, he challenged physicians to do their part in controlling health care costs by not ordering tests and treatments that have no value for patients.2 At that time, it was estimated that a third of tests and treatments ordered by US physicians were of marginal or no value.3
Dr. Brody’s editorial caught the attention of the National Physicians Alliance and eventually many other physician organizations. In 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely initiative; today, the campaign Web site, choosingwisely.org, has a wealth of information and practice recommendations from 78 medical specialty organizations, including the American Academy of Family Physicians (AAFP).
In this month’s issue of JFP, Dr. Kate Rowland has summarized 10 of the most important Choosing Wisely recommendations that apply to family physicians and other primary care clinicians. Here are 5 more recommendations from the Choosing Wisely list of tests and treatments to avoid ordering for your patients:
- Don’t perform pelvic exams on asymptomatic nonpregnant women, unless necessary for guideline-appropriate screening for cervical cancer.
- Don’t routinely screen for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam. For men who want PSA screening, it should be performed only after engaging in shared decision-making.
- Don’t order annual electrocardiograms or any other cardiac screening for low-risk patients without symptoms.
- Don’t routinely prescribe antibiotics for otitis media in children ages 2 to 12 years with nonsevere symptoms when observation is reasonable.
- Don’t use dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.
In total, AAFP lists 18 recommendations (2 additional recommendations have been withdrawn, based on updated evidence) on the Choosing Wisely Web site. I encourage you to review them to see if you should change any of your current patient recommendations.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
1. Hickner J. Count on this no matter who wins the election. J Fam Pract. 2016;65:664.
2. Brody H. Medicine’s ethical responsibility for health care reform—the Top Five list. N Engl J Med. 2010;362:283-285.
3. Fisher ES, Bynum JP, Skinner JS. Slowing the growth of health care costs—lessons from regional variation. N Engl J Med. 2009;360:849-852.
Ruling out PE in pregnancy
ILLUSTRATIVE CASE
A 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.
The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6
Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6
STUDY SUMMARY
Prospective validation of a strategy to diagnose PE in pregnant women
This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.
PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.
Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).
WHAT’S NEW
Clinical probability and D-dimer rule out PE in pregnant women
This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.
CAVEATS
Additional research is still needed
From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.
In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.
CHALLENGES TO IMPLEMENTATION
None to speak of
Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.
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. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.
2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.
3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.
4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.
5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.
6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.
7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.
8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.
9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.
10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.
ILLUSTRATIVE CASE
A 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.
The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6
Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6
STUDY SUMMARY
Prospective validation of a strategy to diagnose PE in pregnant women
This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.
PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.
Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).
WHAT’S NEW
Clinical probability and D-dimer rule out PE in pregnant women
This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.
CAVEATS
Additional research is still needed
From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.
In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.
CHALLENGES TO IMPLEMENTATION
None to speak of
Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.
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 28-year-old G2P1001 at 28 weeks’ gestation presents to your clinic with 1 day of dyspnea and palpitations. Her pregnancy has been otherwise uncomplicated. She reports worsening dyspnea with mild exertion but denies other symptoms, including leg swelling.
The current incidence of venous thromboembolism (VTE) in pregnant women is estimated to be a relatively low 5 to 12 events per 10,000 pregnancies, yet the condition is the leading cause of maternal mortality in developed countries.2,3,4 Currently, there are conflicting recommendations among relevant organization guidelines regarding the use of D-dimer testing to aid in the diagnosis of pulmonary embolism (PE) during pregnancy. Both the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) recommend using D-dimer testing to rule out PE in pregnant women (ESC Class IIa, level of evidence B based on small studies, retrospective studies, and observational studies; GTH provides no grade).5,6
Conversely, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American Thoracic Society (ATS)/Society of Thoracic Radiology recommend against the use of D-dimer testing in pregnant women because pregnant women were excluded from D-dimer validation studies (RCOG and SOGC Grade D; ATS weak recommendation).4,7,8 The American College of Obstetricians and Gynecologists does not have specific recommendations regarding the use of D-dimer testing during pregnancy, but has endorsed the ATS guidelines.4,9 In addition, SOGC recommends against the use of clinical prediction scores (Grade D), and RCOG states that there is no evidence to support their use (Grade C).7,8 The remaining societies do not make a recommendation for or against the use of clinical prediction scores because of the absence of high-quality evidence regarding their use in the pregnant patient population.4,5,6
STUDY SUMMARY
Prospective validation of a strategy to diagnose PE in pregnant women
This multicenter, multinational, prospective diagnostic study involving 395 pregnant women evaluated the accuracy of PE diagnosis across 11 centers in France and Switzerland from August 2008 through July 2016.1 Patients with clinically suspected PE were evaluated in emergency departments. Patients were tested according to a diagnostic algorithm that included pretest clinical probability using the revised Geneva Score for Pulmonary Embolism (www.mdcalc.com/geneva-score-revised-pulmonary-embolism), a clinical prediction tool that uses patient history, presenting symptoms, and clinical signs to classify patients as being at low (0-3/25), intermediate (4-10/25), or high (≥ 11/25) risk;10 high-sensitivity D-dimer testing; bilateral lower limb compression ultrasonography (CUS); computed tomography pulmonary angiography (CTPA); and a ventilation-perfusion (V/Q) scan.
PE was excluded in patients who had a low or intermediate pretest clinical probability score and a negative D-dimer test result (< 500 mcg/L). Patients with a high pretest probability score or positive D-dimer test result underwent CUS, and, if negative, subsequent CTPA. A V/Q scan was performed if the CTPA was inconclusive. If the work-up was negative, PE was excluded.
Untreated pregnant women had clinical follow-up at 3 months. Any cases of suspected VTE were evaluated by a 3-member independent adjudication committee blinded to the initial diagnostic work-up. The primary outcome was the rate of adjudicated VTE events during the 3-month follow-up period. PE was diagnosed in 28 patients (7.1%) and excluded in 367 (clinical probability score and negative D-dimer test result [n = 46], negative CTPA result [n = 290], normal or low-probability V/Q scan [n = 17], and other reason [n = 14]). Twenty-two women received anticoagulation during the follow-up period for other reasons (mainly history of previous VTE disease). No symptomatic VTE events occurred in any of the women after the diagnostic work-up was negative, including among those patients who were ruled out with only the clinical prediction tool and a negative D-dimer test result (rate 0.0%; 95% confidence interval [CI], 0.0%-1%).
WHAT’S NEW
Clinical probability and D-dimer rule out PE in pregnant women
This study ruled out PE in patients with low/intermediate risk as determined by the revised Geneva score and a D-dimer test, enabling patients to avoid further diagnostic testing. This low-cost strategy can be applied easily to the pregnant population.
CAVEATS
Additional research is still needed
From the results of this study, 11.6% of patients (n = 46) had a PE ruled out utilizing the revised Geneva score in conjunction with a D-dimer test result, with avoidance of chest imaging. However, this study was powered for the entire treatment algorithm and was not specifically powered for patients with low- or intermediate-risk pretest probability scores. Since this is the first published prospective diagnostic study of VTE in pregnancy, further research is needed to confirm the findings that a clinical prediction tool and a negative D-dimer test result can safely rule out PE in pregnant women.
In addition, further research is needed to determine pregnancy-adapted D-dimer cut-off values, as the researchers of this study noted that < 500 mcg/L was useful in the first and second trimester, but that levels increased as gestational age increased.
CHALLENGES TO IMPLEMENTATION
None to speak of
Implementing a diagnostic algorithm that incorporates sequential assessment of pretest clinical probability based on the revised Geneva score and a D-dimer measurement should be relatively easy to implement, as both methods are readily available and relatively inexpensive.
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. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.
2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.
3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.
4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.
5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.
6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.
7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.
8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.
9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.
10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.
1. Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy. A multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.
2. Knight M, Kenyon S, Brocklehurst P, et al. Saving lives, improving mothers’ care: lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009-2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford; 2014.
3. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet. 2010;375:500-512.
4. Leung AN, Bull TM, Jaeschke R, et al. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Resp Crit Care Med. 2011;184:1200-1208.
5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41:543-603.
6. Linnemann B, Bauersachs R, Rott H, et al. Working Group in Women’s Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism-position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH). Vasa. 2016;45:87-101.
7. Royal College of Obstetricians & Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. Green‐top Guideline No. 37b. April 2015.
8. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36:527-553.
9. James A, Birsner M, Kaimal A, American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins‐Obstetrics. ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol. 2018;132:e1-e17.
10. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165-171.
PRACTICE CHANGER
Use a clinical probability score to identify patients at low or intermediate risk for pulmonary embolism (PE) and combine that with a high-sensitivity D-dimer test to rule out PE in pregnant women.
STRENGTH OF RECOMMENDATION
B: Prospective diagnostic management outcome study.1
Righini M, Robert-Ebadi H, Elias A, et al. Diagnosis of pulmonary embolism during pregnancy: a multicenter prospective management outcome study. Ann Intern Med. 2018;169:766-773.1
Female cardiac advantage essentially lost after MI
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Women are known to lag 5-10 years behind men in experiencing coronary heart disease (CHD), but new research suggests the gap narrows substantially following a myocardial infarction.
“Women lose a considerable portion, but not all, of their coronary and survival advantage – i.e., the lower event rates – after suffering a MI,” study author Sanne Peters, PhD, George Institute for Global Health, Imperial College London, said in an interview.
Previous studies of sex differences in event rates after a coronary event have produced mixed results and were primarily focused on mortality following MI. Importantly, the studies also lacked a control group without a history of CHD and, thus, were unable to provide a reference point for the disparity in event rates, she explained.
Using the MarketScan and Medicare databases, however, Dr. Peters and colleagues matched 339,890 U.S. adults hospitalized for an MI between January 2015 and December 2016 with 1,359,560 U.S. adults without a history of CHD.
Over a median 1.3 years follow-up, there were 12,518 MIs in the non-CHD group and 27,115 recurrent MIs in the MI group.
The age-standardized rate of MI per 1,000 person-years was 4.0 in women and 6.1 in men without a history of CHD, compared with 57.6 in women and 62.7 in men with a prior MI.
After multivariate adjustment, the women-to-men hazard ratio for MI was 0.64 (95% confidence interval, 0.62-0.67) in the non-CHD group and 0.94 (95% CI, 0.92-0.96) in the prior MI group, the authors reported Oct. 5 in the Journal of the American College of Cardiology
Additional results show the multivariate adjusted women-to-men hazard ratios for three other cardiovascular outcomes follow a similar pattern in the non-CHD and prior MI groups:
- CHD events: 0.53 (95% CI, 0.51-0.54) and 0.87 (95% CI, 0.85-0.89).
- Heart failure hospitalization: 0.93 (95% CI, 0.90-0.96) and 1.02 (95% CI, 1.00-1.04).
- All-cause mortality: 0.72 (95% CI, 0.71-0.73) and 0.90 (95% CI, 0.89-0.92).
“By including a control group of individuals without CHD, we demonstrated that the magnitude of the sex difference in cardiac event rates and survival is considerably smaller among those with prior MI than among those without a history of CHD,” Dr. Peters said.
Of note, the sex differences were consistent across age and race/ethnicity groups for all events, except for heart failure hospitalizations, where the adjusted hazard ratio for women vs. men age 80 years or older was 0.95 for those without a history of CHD (95% CI, 0.91-0.98) and 0.99 (95% CI, 0.96-1.02) for participants with a previous MI.
Dr. Peters said it’s not clear why the female advantage is attenuated post-MI but that one explanation is that women are less likely than men to receive guideline-recommended treatments and dosages or to adhere to prescribed therapies after MI hospitalization, which could put them at a higher risk of subsequent events and worse outcomes than men.
“Sex differences in pathophysiology of CHD and its complications may also explain, to some extent, why the rates of recurrent events are considerably more similar between the sexes than incident event rates,” she said. Compared with men, women have a higher incidence of MI with nonobstructive coronary artery disease and of heart failure with preserved ejection fraction, and evidence-based treatment options are more limited for both conditions.
“After people read this, I think the important thing to recognize is we need to push– as much as we can, with what meds we have, and what data we have – secondary prevention in these women,” Laxmi Mehta, MD, director of preventive cardiology and women’s cardiovascular health at Ohio State University, Columbus, said in an interview.
The lack of a female advantage post-MI should also elicit a “really meaningful conversation with our patients on shared decision-making of why they need to be on medications, remembering on our part to prescribe the medications, remembering to prescribe cardiac rehab, and also reminding our community we do need more data and need to investigate this further,” she said.
In an accompanying editorial, Nanette Wenger, MD, of Emory University, Atlanta, also points out that nonobstructive coronary disease is more common in women and, “yet, guideline-based therapies are those validated for obstructive coronary disease in a predominantly male population but, nonetheless, are applied for nonobstructive coronary disease.”
She advocates for aggressive evaluation and treatment for women with chest pain symptoms as well as early identification of women at risk for CHD, specifically those with metabolic syndrome, preeclampsia, hypertensive disorders of pregnancy, chronic inflammatory conditions, and high-risk race/ethnicity.
“Next, when coronary angiography is undertaken, particularly in younger women, an assiduous search for spontaneous coronary artery dissection and its appropriate management, as well as prompt and evidence-based interventions and medical therapies for an acute coronary event [are indicated],” Dr. Wenger wrote. “However, basic to improving outcomes for women is the elucidation of the optimal noninvasive techniques to identify microvascular disease, which could then enable delineation of appropriate preventive and therapeutic approaches.”
Dr. Peters is supported by a U.K. Medical Research Council Skills Development Fellowship. Dr. Mehta and Dr. Wenger disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Primary prevention of VTE spans a spectrum
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1
VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).
SIDEBAR
Key points: Primary prevention of venous thromboembolism
- Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
- Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
- The risk of travel-related VTE can be reduced by wearing compression stockings.
- The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
- Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
- Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
- Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.
Risk factors
Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7
Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.
Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—obesity, diabetes, smoking, hypertension, hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13
Thrombophilia testing: Not generally useful
Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16
Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19
Continue to: Primary prevention of VTE in the clinic
Primary prevention of VTE in the clinic
There is no single, overarching preventive strategy for VTE in an ambulatory patient (although statins, discussed in a moment, offer some benefit, broadly). There are, however, distinct behavioral characteristics and medical circumstances for which opportunities exist to reduce VTE risk—for example, when a person engages in long-distance travel, receives hormonal therapy, is pregnant, or has cancer. In each scenario, recognizing and mitigating risk are important.
Statins offer a (slight) benefit
There is evidence that statins reduce the risk of VTE—slightly20-23:
- A large randomized, controlled trial showed that rosuvastatin, 20 mg/d, reduced the rate of VTE, compared to placebo; however, the 2-year number needed to treat (NNT) was 349.20 The VTE benefit is minimal, however, compared to primary prevention of cardiovascular disease with statins (5-year NNT = 56).21 The sole significant adverse event associated with statins was new-onset type 2 diabetes (5-year number needed to harm = 235).21
- A subsequent meta-analysis confirmed a small reduction in VTE risk with statins.22 In its 2012 guidelines, ACCP declined to issue a recommendation on the use of statins for VTE prevention.23 When considering statins for primary cardiovascular disease prevention, take the additional VTE prevention into account.
Simple strategies can help prevent travel-related VTE
Travel is a common inciting factor for VTE. A systematic review showed that VTE risk triples after travel of ≥ 4 hours, increasing by 20% with each additional 2 hours.24 Most VTE occurs in travelers who have other VTE risk factors.25 Based on case–control studies,23 guidelines recommend these preventive measures:
- frequent calf exercises
- sitting in an aisle seat during air travel
- keeping hydrated.
A Cochrane review showed that graded compression stockings reduce asymptomatic DVT in travelers by a factor of 10, in high- and low-risk patients.26
VTE risk varies with type of hormonal contraception
Most contraceptives increase VTE risk (TABLE 227,28). Risk with combined oral contraceptives varies with the amount of estrogen and progesterone. To reduce VTE risk with oral contraceptives, patients can use an agent that contains a lower dose of estrogen or one in which levonorgestrel replaces other progesterones.27
Continue to: Studies suggest that the levonorgestrel-releasing...
Studies suggest that the levonorgestrel-releasing intrauterine device and progestin-only pills are not associated with an increase in VTE risk.27 Although the quality of evidence varies, most nonoral hormonal contraceptives have been determined to carry a risk of VTE that is similar to that of combined oral contraceptives.28
In hormone replacement, avoid pills to lower risk
Hormone replacement therapy (HRT) for postmenopausal women increases VTE risk when administered in oral form, with combined estrogen and progestin HRT doubling the risk and estrogen-only formulations having a lower risk.29 VTE risk is highest in the first 6 months of HRT, declining to that of a non-HRT user within 5 years.29 Neither transdermal HRT nor estrogen creams increase the risk of VTE, according to a systematic review.30 The estradiol-containing vaginal ring also does not confer increased risk.29
Pregnancy, thrombophilia, and VTE prevention
VTE affects as many as 0.2% of pregnancies but causes 9% of pregnancy-related deaths.18 The severity of VTE in pregnancy led the American College of Obstetricians and Gynecologists (ACOG) to recommend primary VTE prophylaxis in patients with certain thrombophilias.18 Thrombophilia testing is recommended in patients with proven high-risk thrombophilia in a first-degree relative.18 ACOG recognizes 5 thrombophilias considered to carry a high risk of VTE in pregnancy18:
- homozygous Factor V Leiden
- homozygous prothrombin G20210A mutation
- antithrombin deficiency
- heterozygous Factor V Leiden and prothrombin G20210A mutation
- antiphospholipid antibody syndrome.
ACOG recommends limiting thrombophilia testing to (1) any specific thrombophilia carried by a relative and (2) possibly, the antiphospholipid antibodies anticardiolipin and lupus anticoagulant.18,19 Antiphospholipid testing is recommended when there is a history of stillbirth, 3 early pregnancy losses, or delivery earlier than 34 weeks secondary to preeclampsia.19
Primary VTE prophylaxis is recommended for pregnant patients with a high-risk thrombophilia; low-molecular-weight heparin (LMWH) is safe and its effects are predictable.18 Because postpartum risk of VTE is higher than antepartum risk, postpartum prophylaxis is also recommended with lower-risk thrombophilias18; a vitamin K antagonist or LMWH can be used.18 ACCP and ACOG recommendations for VTE prophylaxis in pregnancy differ slightly (TABLE 316,18,19).
Continue to: Cancer increases risks of VTE and bleeding
Cancer increases risks of VTE and bleeding
Cancer increases VTE risk > 6-fold31; metastases, chemotherapy, and radiotherapy further increase risk. Cancer also greatly increases the risk of bleeding: Cancer patients with VTE have an annual major bleeding rate ≥ 20%.32 Guidelines do not recommend primary VTE prophylaxis for cancer, although American Society of Clinical Oncology guidelines discuss consideration of prophylaxis for select, high-risk patients,33,34 including those with multiple myeloma, metastatic gastrointestinal cancer, or metastatic brain cancer.31,34 Recent evidence (discussed in a moment) supports the use of apixaban for primary VTE prevention during chemotherapy for high-risk cancer.
The Khorana Risk Score (TABLE 435,36) for VTE was developed and validated for use in patients with solid cancer35: A score of 2 conveys nearly a 10% risk of VTE over 6 months.36 A recent study of 550 cancer patients with a Khorana score of ≥ 2—the first evidence of risk-guided primary VTE prevention in cancer—showed that primary prophylaxis with 2.5 mg of apixaban, bid, reduced the risk of VTE (NNT = 17); however, the number needed to harm (for major bleeding) was 59.37 Mortality was not changed with apixaban treatment
Primary VTE prevention in med-surg hospitalizations
The risk of VTE increases significantly during hospitalization, although not enough to justify universal prophylaxis. Recommended prevention strategies for different classes of hospitalized patients are summarized below.
In medically hospitalized patients, risk is stratified with a risk-assessment model. Medically hospitalized patients have, on average, a VTE risk of 1.2%23; 12 risk-assessment models designed to stratify risk were recently compared.38 Two models, the Caprini Score (TABLE 5)39 and the IMPROVE VTE Risk Calculator,40 were best able to identify low-risk patients (negative predictive value, > 99%).38 American Society of Hematology guidelines recommend IMPROVE VTE or the Padua Prediction Score for risk stratification.41 While the Caprini score only designates 11% of eventual VTE cases as low risk, both the IMPROVE VTE and Padua scores miss more than 35% of eventual VTE.38
Because LMWH prophylaxis has been shown to reduce VTE by 40% without increasing the risk of major bleeding, using Caprini should prevent 2 VTEs for every 1000 patients, without an increase in major bleeding and with 13 additional minor bleeding events.42
Continue to: Critically ill patients
Critically ill patients are assumed to be at high risk of VTE and do not require stratification.23 For high-risk patients, prophylaxis with LMWH, low-dose unfractionated heparin (LDUH), or fondaparinux is recommended for the duration of admission.23 For patients at high risk of both VTE and bleeding, mechanical prophylaxis with intermittent pneumatic compression (IPC) is recommended instead of LMWH, LDUH, or fondaparinux.23
Surgery, like trauma (see next page), increases the risk of VTE and has been well studied. Prophylaxis after orthopedic surgery differs from that of other types of surgery.
In orthopedic surgery, risk depends on the procedure. For major orthopedic surgery, including total hip or knee arthroplasty and hip fracture surgery, VTE prophylaxis is recommended for 35 days postsurgically.43 LMWH is the preferred agent, although many other means have been shown to be beneficial.44 A recent systematic review demonstrated that aspirin is not inferior to other medications after hip or knee arthroplasty.45 No mechanical or pharmacotherapeutic prophylaxis is generally recommended after nonmajor orthopedic surgery.43
Nonorthopedic surgery is stratified by risk factors, using Caprini44 (TABLE 539). For medium-risk patients (Caprini score, 3-4) LDUH, LMWH, or IPC is recommended; for high-risk patients (Caprini score, ≥ 5) preventive treatment should combine pharmacotherapeutic and mechanical prophylaxis.46 A recent meta-analysis, comprising 14,776 patients, showed that surgical patients with a Caprini score ≥ 7 had a reduced incidence of VTE when given chemoprophylaxis, whereas patients whose score is < 7 do not benefit from chemoprophylaxis.43 When bleeding risk is high, IPC is recommended as sole therapy.43 Prophylaxis is not recommended when risk (determined by the Caprini score) is low.46
Post-hospitalization. Risk of VTE can persist for as long as 90 days after hospitalization; this finding has led to evaluation of the benefit of prolonged chemoprophylaxis.23 Extended-duration LMWH prophylaxis decreases the incidence of VTE, but at the cost of increased risk of major bleeding.47 Based on this evidence, guidelines recommend against prolonged-duration anticoagulation.23 A 2016 trial showed that 35 days of the direct-acting anticoagulant betrixaban reduced the risk of symptomatic VTE events, compared to 10 days of LMWH (NNT = 167), without increased risk of bleeding.48 This is a limited benefit, however, that is unlikely to change guideline recommendations.
Continue to: Trauma
Trauma: VTE risk increases with severity
Trauma increases the risk of VTE considerably. A national study showed that 1.5% of admitted trauma patients experienced VTE during hospitalization and that 1.2% were readmitted for VTE within 1 year.49 As many as 32% of trauma patients admitted to the intensive care unit experience VTE despite appropriate prophylaxis.50 A Cochrane Review51 found that:
- prophylaxis significantly reduces DVT risk
- pharmacotherapeutic prophylaxis is more effective than mechanical prophylaxis
- LMWH is more effective than LDUH.
Guidelines recommend that major trauma patients receive prophylaxis with LMWH, LDUH, or IPC.46
CORRESPONDENCE
Michael J. Arnold, MD, CDR, MC, USN; Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Jacksonville, FL 32214; [email protected].
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
1. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010. 38(4 suppl):S495-S501.
2. Tagalakis V, Patenaude V, Kahn SR, et al. Incidence of and mortality from venous thromboembolism in a real-world population: the Q-VTE Study Cohort. Am J Med. 2013;126:832.e13-e21.
3. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010. 362:2155-2165.
4. Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004;117:19-25.
5. Goldhaber SZ. Venous thromboembolism: epidemiology and magnitude of the problem. Best Pract Res Clin Haematol. 2012;25:235-242.
6. Stone J, Hangge P, Albadawi H, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017;7(suppl 3):S276-S284.
7. Olaf M, Cooney R. Deep venous thrombosis. Emerg Med Clin North Am. 2017;35:743-770.
8. Sajid MS, Ahmed N, Desai M, et al. Upper limb deep vein thrombosis: a literature review to streamline the protocol for management. Acta Haematol. 2007;118:10-18.
9. Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med. 2004;351:268-277.
10. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009;151:180-190.
11. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Col Cardiol. 2010;56:1-7.
12. Yang G, De Staercke C, Hooper WC. The effects of obesity on venous thromboembolism: a review. Open J Prev Med. 2012;2:499-509.
13. Severinsen MT, Kristensen SR, Johnsen SP, et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost. 2009;7:1297-1303.
14. Coppens M, Reijnders JH, Middeldorp S, et al. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6:1474-1477.
15. Choosing Wisely. American Society of Hematology. Ten things physicians and patients should question. www.choosingwisely.org/societies/american-society-of-hematology/. Accessed September 28, 2020.
16. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e691S-e736S.
17. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. 2005;3:459-464.
18. Practice Bulletin No. 197: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2018;132:e18-e34.
19. Committee on Practice Bulletins—Obstetrics, American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012;120:1514-1521.
20. Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851-1861.
21. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013(1):CD004816.
22. Squizzato A, Galli M, Romualdi E, et al. Statins, fibrates, and venous thromboembolism: a meta-analysis. Eur Heart J. 2010;31:1248-1256.
23. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e195S-e226S.
24. Kelman CW, Kortt MA, Becker NG, et al. Deep vein thrombosis and air travel: record linkage study. BMJ. 2003;327:1072.
25. Johnston RV, Hudson MF; . Travelers’ thrombosis. Aviat Space Environ Med. 2014;85:191-194.
26. Clarke MJ, Broderick C, Hopewell S, et al. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2016;9:CD004002.
27. van Hylckama Vlieg A, Middledorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257-266.
28. Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception. 2017;95:130-139.
29. Lekovic D, Miljic P, Dmitrovic A, et al. How do you decide on hormone replacement therapy in women with risk of venous thromboembolism? Blood Rev. 2017;31:151-157.
30. Rovinski D, Ramos RB, Fighera TM, et al. Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: a systematic review and meta-analysis. Thromb Res. 2018;168:83-95.
31. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.
32. Kamphuisen PW, Beyer-Westendorf J. Bleeding complications during anticoagulant treatment in patients with cancer. Thromb Res. 2014;133(suppl 2):S49-S55.
33. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315-352.
34. Lyman GH, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2013;31:2189-2204.
35. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
36. Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-5382.
37. Carrier M, Abou-Nassar K, Mallick R, et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711-719.
38. Cobben MRR, Nemeth B, Lijfering WM, et al. Validation of risk assessment models for venous thrombosis in hospitalized medical patients. Res Pract Thromb Haemost. 2019;3:217-225.
39. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70-78.
40. Spyropoulos AC, Anderson FA Jr, FitzGerald G, et al; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-714.
41. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther. 2007;29:2395-2405.
42. HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv. 2018;2:3198-3225.
43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e278S-e325S.
44. Pannucci CJ, Swistun L, MacDonald JK, et al. Individualized venous thromboembolism risk stratification using the 2005 Caprini Score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg. 2017;265:1094-1103.
45. Matharu GS, Kunutsor SK, Judge A, et al. Clinical effectiveness and safety of aspirin for venous thromboembolism prophylaxis after total hip and knee replacement: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2020;180:376-384.
46. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 suppl):e227S-e277S.
47. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recent reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.
48. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544.
49. Rattan R, Parreco J, Eidelson SA, et al. Hidden burden of venous thromboembolism after trauma: a national analysis. J Trauma Acute Care Surg. 2018;85:899-906.
50. Yumoto T, Naito H, Yamakawa Y, et al. Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening. Acute Med Surg. 2017;4:394-400.
51. Barrera LM, Perel P, Ker K, et al. Thromboprophylaxis for trauma patients. Cochrane Database Syst Rev. 2013(3):CD008303.
PRACTICE RECOMMENDATIONS
› Consider the mild reduction in the risk of venous thromboembolism (VTE) provided by statins when contemplating their use for cardiovascular disease prevention. B
› Avoid testing for thrombophilia to determine the risk of VTE, except in pregnant patients who meet criteria for antiphospholipid syndrome or have a family history of VTE. B
› Recommend an intrauterine device or progestin-only pill for contraception if the patient’s risk of VTE is high. B
› Stratify hospitalized medical and nonorthopedic surgical patients by risk score to determine the need for VTE prophylaxis. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
Don’t discount ultrapotent topical corticosteroids for vulvar lichen sclerosus
according to an expert speaking at the virtual conference on diseases of the vulva and vagina.
If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO2 laser treatments may help patients with refractory disease.
Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.
Patients then should continue treatment, but less frequently or with a lower potency steroid.
Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.
Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.
After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.
“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.
To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”
Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.
Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
Beyond topical steroids
“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.
For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.
Intralesional corticosteroid injections are one option.
Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.
Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
What about lasers?
Fractional CO2 laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)
“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”
Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.
If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.
The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.
“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”
Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.
according to an expert speaking at the virtual conference on diseases of the vulva and vagina.
If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO2 laser treatments may help patients with refractory disease.
Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.
Patients then should continue treatment, but less frequently or with a lower potency steroid.
Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.
Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.
After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.
“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.
To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”
Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.
Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
Beyond topical steroids
“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.
For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.
Intralesional corticosteroid injections are one option.
Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.
Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
What about lasers?
Fractional CO2 laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)
“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”
Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.
If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.
The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.
“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”
Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.
according to an expert speaking at the virtual conference on diseases of the vulva and vagina.
If needed, intralesional steroid injections or calcineurin inhibitors can be added to a topical corticosteroid regimen, Libby Edwards, MD, suggested at the meeting, hosted by the International Society for the Study of Vulvovaginal Disease. In addition, early reports indicate that newer interventions such as fractional CO2 laser treatments may help patients with refractory disease.
Still, “there is no question, there is no argument: First-, second- and third-line treatment for lichen sclerosus is an ultrapotent or superpotent topical corticosteroid,” she said. Steroids include halobetasol, clobetasol, or betamethasone dipropionate in augmented vehicle ointment once or twice per day. Patients should continue this regimen until the skin texture is normal or the disease is controlled as well as possible, which usually takes several months, said Dr. Edwards, of Southeast Vulvar Clinic in Charlotte, N.C.
Patients then should continue treatment, but less frequently or with a lower potency steroid.
Although corticosteroids are not Food and Drug Administration–approved for the treatment of lichen sclerosus, double-blind, placebo-controlled trials support their use, Dr. Edwards said.
Getting patients to use topical corticosteroids as directed can be a challenge, however, and patient education is crucial.
After about 10 days, many patients start to feel better and stop the medication prematurely, which may lead to recurrence.
“That is such an important counseling point,” Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif., said during a panel discussion. “Tell them, listen, I may not see you back for a couple months, and you may start feeling better sooner. But I want you to keep using this at this frequency so that when you come back we can make a good decision about whether you’re ready” for a lower potency regimen.
To encourage daily use, Hope K. Haefner, MD, asks patients whether they brush their teeth every night. “When they say yes, I tell them to put the steroid ointment by their toothpaste and use it after brushing,” Dr. Haefner, the Harold A. Furlong Professor of Women’s Health at Michigan Medicine in Ann Arbor, said during the discussion. “But don’t mix up the tubes.”
Once lichen sclerosus is controlled, options include decreasing the superpotent steroid to once, three times per week or changing to a midpotency steroid such as triamcinolone ointment every day, Dr. Edwards said.
Evidence suggests that controlling lichen sclerosus may prevent squamous cell carcinoma and scarring. In a study of more than 500 patients, about 70% complied with treatment instructions, whereas about 30% were considered partially compliant (JAMA Dermatol. 2015 Oct;151[10]:1061-7.). Patients who adhered to their therapy were less likely to have cancer or ongoing scarring during an average of 4.7 years of follow-up.
Beyond topical steroids
“Almost always, topical steroids are all you need,” said Dr. Edwards. “Before I go beyond that, I think of other issues that may be causing symptoms,” such as atrophic vagina, steroid dermatitis, or vulvodynia.
For patients with refractory lichen sclerosus, other treatments “can add more oomph to your topical steroid, but they are not better,” she said.
Intralesional corticosteroid injections are one option.
Another option is adding a calcineurin inhibitor such as tacrolimus or pimecrolimus, although these medications can burn with application and irritate. In addition, they carry warnings about rare cases of cancer associated with their use.
Dr. Edwards also uses methotrexate, which is supported by case reports and an open-label study. In a recently published study that included 21 patients with vulvar lichen sclerosus and 24 patients with extragenital lichen sclerosus, about half improved after receiving methotrexate (Dermatol Ther. 2020 Apr 29;e13473.).
What about lasers?
Fractional CO2 laser treatments, which are pulsed to minimize damage from heat, have “a lot of providers very excited,” Dr. Edwards said. In one open-label study of 40 patients, most reported a decrease in symptoms. (J Low Genit Tract Dis. 2020 Apr;24[2]:225-8.)
“We’re awaiting blinded, controlled studies,” Dr. Edwards said. “We don’t have those available yet although they are in progress.”
Ten of Dr. Edwards’ patients who did not improve enough with medication have received laser treatments. One patient stopped laser therapy after one treatment. One did not improve. Two were completely cleared, and six had significant improvement.
If patients who improved stopped steroids against recommendations, lichen sclerosus recurred, Dr. Edwards said.
The ISSVD does not recommend laser for the routine treatment of lichen sclerosus because of a lack of adequate studies and long-term safety data and biologic implausibility, Dr. Edwards noted (J Low Genit Tract Dis. 2019 Apr;23[2]:151-60.) Laser treatments for lichen sclerosus should not be used outside of clinical trials or without special arrangements for clinical governance, consent, and audit, according to a consensus document from the society.
“I mostly agree with that,” Dr. Edwards said. “But I now think that this is a reasonable thing to use when other treatments have been exhausted.”
Dr. Edwards and Dr. Venkatesan had no conflicts of interest. Dr. Haefner is an author for UpToDate.
EXPERT ANALYSIS FROM THE ISSVD BIENNIAL CONFERENCE
Choosing Wisely: 10 practices to stop—or adopt—to reduce overuse in health care
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
When medical care is based on consistent, good-quality evidence, most physicians adopt it. However, not all care is well supported by the literature and may, in fact, be overused without offering benefit to patients. Choosing Wisely, at www.choosingwisely.org, is a health care initiative that highlights screening and testing recommendations from specialty societies in an effort to encourage patients and clinicians to talk about how to make high-value, effective health care decisions and avoid overuse. (See “Test and Tx overutilization: A bigger problem than you might think"1-3).
SIDEBAR
Test and Tx overutilization: A bigger problem than you might think
Care that isn’t backed up by the medical literature is adopted by some physicians and not adopted by others, leading to practice variations. Some variation is to be expected, since no 2 patients require exactly the same care, but substantial variations may be a clue to overuse.
A 2006 analysis of inpatient lab studies found that doctors ordered an average of 2.96 studies per patient per day, but only 29% of these tests (0.95 test/patient/day) contributed to management.1 A 2016 systematic review found more than 800 studies on overuse were published in a single year.2 One study of thyroid nodules followed almost 1000 patients with nodules as they underwent routine follow-up imaging. At the end of the study, 7 were found to have cancer, but of those, only 3 had enlarging or changing nodules that would have been detected with the follow-up imaging being studied. Three of the cancers were stable in size and 1 was found incidentally.3
Enabling physician and patient dialogue. The initiative began in 2010 when the American Board of Internal Medicine convened a panel of experts to identify low-value tests and therapies. Their list took the form of a “Top Five Things” that may not be high value in patient care, and it used language tailored to patients and physicians so that they could converse meaningfully. Physicians could use the evidence to make a clinical decision, and patients could feel empowered to ask informed questions about recommendations they received. The initiative has now expanded to include ways that health care systems can reduce low-value interventions.
Scope of participation. Since the first Choosing Wisely recommendations were published in 2013, more than 80 professional associations have contributed lists of their own. Professional societies participate voluntarily. The American Academy of Family Physicians (AAFP), Society of General Internal Medicine, and American Academy of Pediatrics (AAP) have contributed lists relevant to primary care. All Choosing Wisely recommendations can be searched or sorted by specialty organization. Recommendations are reviewed and revised regularly. If the evidence becomes conflicted or contradictory, recommendations are withdrawn.
Making meaningful improvements by Choosing Wisely
Several studies have shown that health care systems can implement Choosing Wisely recommendations to reduce overuse of unnecessary tests. A 2015 study examined the effect of applying a Choosing Wisely recommendation to reduce the use of continuous pulse oximetry in pediatric inpatients with asthma, wheezing, or bronchiolitis. The recommendation, from the Society of Hospital Medicine–Pediatric Hospital Medicine, advises against continuous pulse oximetry in children with acute respiratory illnesses unless the child is using supplemental oxygen.4 This study, done at the Cincinnati Children’s Hospital Medical Center, found that within 3 months of initiating a protocol on all general pediatrics floors, the average time on pulse oximetry after meeting clinical goals decreased from 10.7 hours to 3.1 hours. In addition, the percentage of patients who had their continuous pulse oximetry stopped within 2 hours of clinical stability (a goal time) increased from 25% to 46%.5
Patients are important drivers of health care utilization. A 2003 study showed that physicians are more likely to order referrals, tests, and prescriptions when patients ask for them, and that nearly 1 in 4 patients did so.6 A 2002 study found that physicians granted all but 3% of patient’s requests for orders or tests, and that fulfilling requests correlated with patient satisfaction in the specialty office studied (cardiology) but not in the primary care (internal medicine) office.7
From its inception, Choosing Wisely has considered patients as full partners in conversations about health care utilization. Choosing Wisely partners with Consumer Reports to create and disseminate plain-language summaries of recommendations. Community groups and physician organizations have also participated in implementation efforts. In 2018, Choosing Wisely secured a grant to expand outreach to diverse or underserved communities.
Choosing Wisely recommendations are not guidelines or mandates. They are intended to be evidence-based advice from a specialty society to its members and to patients about care that is often unnecessary. The goal is to create a conversation and not to eliminate these services from ever being offered or used.
Continue to: Improve your practice with these 10 primary care recommendations
Improve your practice with these 10 primary care recommendations
1 Avoid imaging studies in early acute low back pain without red flags.
Both the AAFP and the American Society of Anesthesiologists recommend against routine X-rays, magnetic resonance imaging, and computed tomography (CT) scans in the first 6 weeks of acute low back pain (LBP).8,9 The American College of Emergency Physicians (ACEP) recommends against routine lumbar spine imaging for emergency department (ED) patients.10 In all cases, imaging is indicated if the patient has any signs or symptoms of neurologic deficits or other indications, such as signs of spinal infection or fracture. However, as ACEP notes, diagnostic imaging does not typically help identify the cause of acute LBP, and when it does, it does not reduce the time to symptom improvement.10
2 Prescribe oral contraceptives on the basis of a medical history and a blood pressure measurement. No routine pelvic exam or other physical exam is necessary.
This AAFP recommendation11 is based on clinical practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) and other research.12 The ACOG practice guideline supports provision of hormonal contraception without a pelvic exam, cervical cancer (Pap) testing, urine pregnancy testing, or testing for sexually transmitted infections. ACOG guidelines also support over-the-counter provision of hormonal contraceptives, including combined oral contraceptives.12
3 Stop recommending daily self-glucose monitoring for patients with diabetes who are not using insulin.
Both the AAFP and the Society for General Internal Medicine recommend against daily blood sugar checks for people who do not use insulin.13,14 A Cochrane review of 9 trials (3300 patients) found that after 6 months, hemoglobin A1C was reduced by 0.3% in people who checked their sugar daily compared with those who did not, but this difference was not significant after a year.15 Hypoglycemic episodes were more common in the “checking” group, and there were no differences in quality of life. A qualitative study found that blood sugar results had little impact on patients’ motivation to change behavior.16
4 Don’t screen for herpes simplex virus (HSV) infection in asymptomatic adults, even those who are pregnant.
This AAFP recommendation17 comes from a US Preventive Services Task Force (USPSTF) Grade D recommendation.18 Most people with positive HSV-2 serology have had an outbreak; even those who do not think they have had one will realize that they had the symptoms once they hear them described.18 With available tests, 1 in 2 positive results for HSV-2 among asymptomatic people will be a false-positive.18
There is no known cure, intervention, or reduction in transmission for infected patients who do not have symptoms.18 Also, serologically detected HSV-2 does not reliably predict genital herpes; and HSV-1 has been found to cause an increasing percentage of genital infection cases.18
Continue to: 5 Don't screen for testicular cancer in asymptomatic individuals
5 Don’t screen for testicular cancer in asymptomatic individuals.
This AAFP recommendation19 also comes from a USPSTF Grade D recommendation.20 A 2010 systematic review found no evidence to support screening of asymptomatic people with a physical exam or ultrasound. All available studies involved symptomatic patients.20
6 Stop recommending cough and cold medicines for children younger than 4 years.
The AAP recommends that clinicians discourage the use of any cough or cold medicine for children in this age-group.21 A 2008 study found that more than 7000 children annually presented to EDs for adverse events from cough and cold medicines.22 Previous studies found no benefit in reducing symptoms.23 In children older than 12 months, a Cochrane review found that honey has a modest benefit for cough in single-night trials.24
7 Avoid performing serum allergy panels.
The American Academy of Allergy, Asthma, and Immunology discourages the use of serum panel testing when patients present with allergy symptoms.25 A patient can have a strong positive immunoglobulin E (IgE) serum result to an allergen and have no clinical allergic symptoms or can have a weak positive serum result and a strong clinical reaction. Targeted skin or serum IgE testing—for example, testing for cashew allergy in a patient known to have had a reaction after eating one—is reasonable.26
8 Avoid routine electroencephalography (EEG), head CT, and carotid ultrasound as initial work-up for simple syncope in adults.
These recommendations, from the American Epilepsy Society,27 ACEP,28 American College of Physicians,29 and American Academy of Neurology (AAN),30 emphasize the low yield of routine work-ups for patients with simple syncope. The AAN notes that 40% of people will experience syncope during adulthood and most will not have carotid disease, which generally manifests with stroke-like symptoms rather than syncope. One study found that approximately 1 in 8 patients referred to an epilepsy clinic had neurocardiogenic syncope rather than epilepsy.31
EEGs have high false-negative and false-positive rates, and history-taking is a better tool with which to make a diagnosis. CT scans performed in the ED were found to contribute to the diagnosis of simple syncope in fewer than 2% of cases of syncope, compared with orthostatic blood pressure (25% of cases).32
Continue to: 9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age
9 Wait to refer children with umbilical hernias to pediatric surgery until they are 4 to 5 years of age.
The AAP Section on Surgery offers evidence that the risk-benefit analysis strongly favors waiting on intervention.33 About 1 in 4 children will have an umbilical hernia, and about 85% of cases will resolve by age 5. The strangulation rate with umbilical hernias is very low, and although the risk of infection with surgery is likewise low, the risk of recurrence following surgery before the age of 4 is as high as 2.4%.34 The AAP Section on Surgery recommends against strapping or restraining the hernia, as well.
10 Avoid using appetite stimulants, such as megesterol, and high-calorie nutritional supplements to treat anorexia and cachexia in older adults.
Instead, the American Geriatrics Society recommends that physicians encourage caregivers to serve appealing food, provide support with eating, and remove barriers to appetite and nutrition.35 A Cochrane review showed that high-calorie supplements, such as Boost or Ensure, are associated with very modest weight gain—about 2% of weight—but are not associated with an increased life expectancy or improved quality of life.36
Prescription appetite stimulants are associated with adverse effects and yield inconsistent benefits in older adults. Megesterol, for example, was associated with headache, gastrointestinal adverse effects, insomnia, weakness, and fatigue. Mirtazapine is associated with sedation and fatigue.37
CORRESPONDENCE
Kathleen Rowland, MD, MS, Rush Copley Family Medicine Residency, Rush Medical College, 600 South Paulina, Kidston House Room 605, Chicago IL 60612; [email protected].
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
1. Miyakis S, Karamanof G, Liontos M, et al. Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy. Postgrad Med J. 2006;82:823-829.
2. Morgan DJ, Dhruva SS, Wright SM, et al. Update on medical overuse: a systematic review. JAMA Intern Med. 2016;176:1687-1692.
3. Durante C, Costante G, Lucisano G, et al. The natural history of benign thyroid nodules. JAMA. 2015;313:926-935.
4. Choosing Wisely. Society of Hospital Medicine—Pediatric hospital medicine. Don’t use continuous pulse oximetry routinely in children with acute respiratory illness unless they are on supplemental oxygen. www.choosingwisely.org/clinician-lists/society-hospital-medicine-pediatric-continuous-pulse-oximetry-in-children-with-acute-respiratory-illness/. Accessed September 28, 2020.
5. Schondelmeyer AC, Simmons JM, Statile AM, et al. Using quality improvement to reduce continuous pulse oximetry use in children with wheezing. Pediatrics. 2015;135:e1044-e1051.
6. Kravitz RL, Bell RA, Azari R, et al. Direct observation of requests for clinical services in office practice: what do patients want and do they get it? Arch Intern Med. 2003;163:1673-1681.
7. Kravitz RL, Bell RA, Franz CE, et al. Characterizing patient requests and physician responses in office practice. Health Serv Res. 2002;37:217-238.
8. Choosing Wisely. American Academy of Family Physicians. Don’t do imaging for low back pain within the first six weeks, unless red flags are present. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-imaging-low-back-pain/. Accessed September 28, 2020.
9. Choosing Wisely. American Society of Anesthesiologists–Pain Medicine. Avoid imaging studies (MRI, CT or X-rays) for acute low back pain without specific indications. www.choosingwisely.org/clinician-lists/american-society-anesthesiologists-imaging-studies-for-acute-low-back-pain/. Accessed September 28, 2020.
10. Choosing Wisely. American College of Emergency Physicians. Avoid lumbar spine imaging in the emergency department for adults with non-traumatic back pain unless the patient has severe or progressive neurologic deficits or is suspected of having a serious underlying condition (such as vertebral infection, cauda equina syndrome, or cancer with bony metastasis). www.choosingwisely.org/clinician-lists/acep-lumbar-spine-imaging-in-the-ed/. Accessed September 28, 2020.
11. Choosing Wisely. American Academy of Family Physicians. Don’t require a pelvic exam or other physical exam to prescribe oral contraceptive medications. www.choosingwisely.org/clinician-lists/american-academy-family-physicians-pelvic-or-physical-exams-to-prescribe-oral-contraceptives/. Accessed September 28, 2020.
12. Over-the-counter access to hormonal contraception. ACOG Committee Opinion, Number 788. Obstet Gynecol. 2019;134:e96-e105. https://journals.lww.com/greenjournal/Fulltext/2019/10000/Over_the_Counter_Access_to_Hormonal_Contraception_.46.aspx. Accessed September 28, 2020.
13. Choosing Wisely. American Academy of Family Physicians. Don’t routinely recommend daily home glucose monitoring for patients who have Type 2 diabetes mellitus and are not using insulin. www.choosingwisely.org/clinician-lists/aafp-daily-home-glucose-monitoring-for-patients-with-type-2-diabetes. Accessed September 28, 2020.
14. Choosing Wisely. Society of General Internal Medicine. Don’t recommend daily home finger glucose testing in patients with Type 2 diabetes mellitus not using insulin. www.choosingwisely.org/clinician-lists/society-general-internal-medicine-daily-home-finger-glucose-testing-type-2-diabetes-mellitus/. Accessed September 28, 2020.
15. Malanda UL, Welschen LM, Riphagen II, et al. Self‐monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin. Cochrane Database Syst Rev. 2012(1):CD005060.
16. Peel E, Douglas M, Lawton J. Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients’ perspectives. BMJ. 2007;335:493.
17. Choosing Wisely. American Academy of Family Physicians. Don’t screen for genital herpes simplex virus infection (HSV) in asymptomatic adults, including pregnant women. www.choosingwisely.org/clinician-lists/aafp-genital-herpes-screening-in-asymptomatic-adults/. Accessed September 28, 2020.
18. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Serologic screening for genital herpes infection: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:2525-2530.
19. Choosing Wisely. American Academy of Family Physicians. Don’t screen for testicular cancer in asymptomatic adolescent and adult males. www.choosingwisely.org/clinician-lists/aafp-testicular-cancer-screening-in-asymptomatic-adolescent-and-adult-men/. Accessed September 28, 2020.
20. Lin K, Sharangpani R. Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153:396-399.
21. Choosing Wisely. American Academy of Pediatrics. Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Accessed September 28, 2020.
22. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:783-787.
23. Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006;18:184-188.
24. Oduwole O, Udoh EE, Oyo‐Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev. 2018(4):CD007094.
25. Choosing Wisely. American Academy of Allergy, Asthma & Immunology. Don’t perform unproven diagnostic tests, such as immunoglobulin G(lgG) testing or an indiscriminate battery of immunoglobulin E(lgE) tests, in the evaluation of allergy. www.choosingwisely.org/clinician-lists/american-academy-allergy-asthma-immunology-diagnostic-tests-for-allergy-evaluation/. Accessed September 28, 2020.
26. Cox L, Williams B, Sicherer S, et al. Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology Specific IgE Test Task Force. Ann Allergy Asthma Immunol. 2008;101:580-592.
27. Choosing Wisely. American Epilepsy Society. Do not routinely order electroencephalogram (EEG) as part of initial syncope work-up. www.choosingwisely.org/clinician-lists/aes-eeg-as-part-of-initial-syncope-work-up/. Accessed September 28, 2020.
28. Choosing Wisely. American College of Emergency Physicians. Avoid CT of the head in asymptomatic adult patients in the emergency department with syncope, insignificant trauma and a normal neurological evaluation. www.choosingwisely.org/clinician-lists/acep-avoid-head-ct-for-asymptomatic-adults-with-syncope/. Accessed September 28, 2020.
29. Choosing Wisely. American College of Physicians. In the evaluation of simple syncope and a normal neurological examination, don’t obtain brain imaging studies (CT or MRI). www.choosingwisely.org/clinician-lists/american-college-physicians-brain-imaging-to-evaluate-simple-syncope/. Accessed September 28, 2020.
30. Choosing Wisely. American Academy of Neurology. Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. www.choosingwisely.org/clinician-lists/american-academy-neurology-carotid-artery-imaging-for-simple-syncope/. Accessed September 28, 2020.
31. Josephson CB, Rahey S, Sadler RM. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can J Neurol Sci. 2007;34:221-224.
32. Mendu ML, McAvay G, Lampert R, et al. Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch Intern Med. 2009;169:1299-1305.
33. Choosing Wisely. American Academy of Pediatrics–Section on Surgery. Avoid referring most children with umbilical hernias to a pediatric surgeon until around age 4-5 years. www.choosingwisely.org/clinician-lists/aap-sosu-avoid-surgery-referral-for-umbilical-hernias-until-age-4-5/. Accessed September 28, 2020.
34. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40:1009-1014.
35. Choosing Wisely. American Geriatrics Society. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, discontinue medications that may interfere with eating, provide appealing food and feeding assistance, and clarify patient goals and expectations. www.choosingwisely.org/clinician-lists/american-geriatrics-society-prescription-appetite-stimulants-to-treat-anorexia-cachexia-in-elderly/. Accessed September 28, 2020.
36. Milne AC, Potter J, Vivanti A, et al. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Sys Rev. 2009(2):CD003288.
37. Fox CB, Treadway AK, Blaszczyk AT, et al. Megestrol acetate and mirtazapine for the treatment of unplanned weight loss in the elderly. Pharmacotherapy. 2009;29:383-397.
Enhanced recovery program improves outcomes after cesarean delivery
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
according to recent research published in Obstetrics & Gynecology.
Luciana Mullman, MPH, of Saint Barnabas Medical Center in Livingston, N.J., and colleagues used a pre-post study design to evaluate the effectiveness of ERAS at a tertiary care institution after implementing the program for patients undergoing scheduled or emergent cesarean delivery between December 2018 and August 2019. The researchers compared the rates of opioid use, length of stay, and costs of care for patients undergoing cesarean section after ERAS was implemented with those outcomes for cesarean deliveries at the center prior to ERAS between January 2018 and December 2018.
The ERAS program
ERAS was described in the study as incorporating a preoperative strategy, intraoperative management and postoperative care for cesarean delivery. The preoperative strategy consisted of a patient guidebook and a personal meeting for patient education on what to expect for preoperative and postoperative experiences as well as instructions leading up to the surgery.
For intraoperative management, intravenous opioids were minimized and replaced with neuraxial opioids when appropriate. The patient’s body temperature was monitored and controlled during the intraoperative pathway, and fluid balance was maintained. To prevent postoperative nausea and vomiting, IV ondansetron at a dose of 4 mg was started at the beginning of the cesarean delivery. When the cesarean delivery was complete, an anesthesiologist administered transversus abdominis plane blocks with 0.3% ropivacaine 30 mL on each side before the patient moved to the recovery area.
Postoperatively, the patient’s catheter was removed in the recovery room, and then transferred to postpartum floors if appropriate based on patient status. Patients began resuming a clear liquid diet 1 hour after cesarean delivery and a regular diet 6 hours after delivery. At 6 hours after surgery, the patient was out of bed and moving; walks around the nursing unit were scheduled three times per day at minimum. For pain, patients were given a 1,000-mg acetaminophen tablet every 8 hours, a 600-mg ibuprofen tablet every 6 hours, and dextromethorphan 30 mg/mL every 8 hours, with oral oxycodone 5 mg administered after physician evaluation for breakthrough pain.
Overall, there were 3,679 cesarean deliveries in the study, which included 2,171 deliveries prior to ERAS implementation and 1,508 cesarean deliveries after implementation. Patients with a scheduled cesarean delivery prior to ERAS implementation received no consistent educational program for anticipating cesarean delivery. After implementation, those patients with scheduled cesarean delivery received the full preoperative, intraoperative, and postoperative pathway, while emergent cesarean cases included the intraoperative management and postoperative care, but did not contain the preoperative component.
Improved outcomes after ERAS
The researchers found a significant decrease in the use of opioids after implementing ERAS at the center, with 24% of patients receiving opioids after ERAS, compared with 84% of patients prior to ERAS (odds ratio, 16.8; 95% confidence interval, 14.3-19.9; P < .001). These reductions in opioid use from the pre- and postimplementation periods were similar for patients with scheduled cesarean deliveries (85% vs. 27%; OR, 14.9; 95% CI, 12.2-18.3; P < .001) and emergent cesarean deliveries (83% vs. 19%; OR, 21.4; 95% CI, 16.1-28.7; P < .001).
There was also a significant reduction in total morphine milligram equivalents (MME) for patients who received opioids after ERAS (median, 15.0 MME), compared with before (median, 56.5 MME) implementing ERAS (mean relative change, 0.32; 95% CI, 0.28-0.35; P < .001). These results also were significant among both scheduled (median 59.9 vs. 15.0 MME; mean relative change, 0.31; 95% CI, 0.27-0.36; P < .001) and emergent (median 56.5 vs. 15.0 MME; mean relative change, 0.95; 95% CI, 0.89-1.01; P < .001) cesarean deliveries.
The overall length of stay after cesarean delivery significantly decreased after ERAS from an average of 3.2 days to 2.7 days (mean relative change, 0.82, 95% CI, 0.80-0.83; P < .001), and was significant in both scheduled (3.2 vs. 2.7 days; mean relative change, 0.83; 95% CI, 0.81-0.85; P < .001) and emergent (3.1 vs. 2.5 days; mean relative change, 0.80; 95% CI, 0.77-0.82; P < .001) groups. While the number of patients discharged within 2 days increased from 9% to 49% after ERAS implementation, there was no significant difference overall or in either group regarding 30-day readmission. The researchers also noted the median direct costs of cesarean delivery decreased by $349 per case after starting ERAS (mean relative change, 0.93; 95% CI, 0.91-0.95).
ERAS implementation lagging in obstetrics
In an interview, Iris Krishna, MD, MPH, a maternal-fetal medicine specialist at Emory University, Atlanta, said the ERAS approach has been used successfully in other surgical specialties but has “lagged” in obstetrics. “To date, there has been less attention in improving perioperative outcomes for women undergoing cesarean delivery, the most common abdominal surgery for women.”
Dr. Krishna said this study shows ERAS can be used in obstetrics to improve outcomes after cesarean section without increasing readmission rates. “Overall, this study demonstrates that ERAS can be successfully implemented for cesarean delivery as it has been for a variety of surgical specialties. ERAS for cesarean delivery can improve the quality of patient care while reducing health care costs.”
Women in the postpartum and postoperative period could benefit from ERAS as they recover from surgery and adjust to becoming a new mother, Dr. Krishna noted. “The goal of ERAS is to help patients return to physiological functioning as quickly as possible. Improving postoperative recovery can help with mother-infant bonding and breastfeeding.
“Implementation of a standardized approach for cesarean delivery has the potential to reduce health disparities and the disproportionately high rates of maternal morbidity and mortality in the United States,” she added. “ERAS for cesarean delivery also has the potential to address the opioid epidemic amongst reproductive-age women by improving postcesarean pain management and reducing opioid prescribing.”
Dr. Krishna also explained that an ERAS program would be feasible to implement in most centers. “It will require a shift of some elements of care from the inpatient to outpatient setting, but theoretically feasible as pregnant women frequently undergo many clinic visits during their pregnancy course.
“Education on ERAS for cesarean delivery can be implemented into prenatal care visits. ERAS implementation will also require a multidisciplinary team approach that includes obstetrics, anesthesia, nursing, pharmacy, pediatrics – all key stakeholders that will need to ‘buy in’ or be willing to support the protocol to ensure its success. As in this study, it would be helpful for hospitals to have an ERAS coordinator to champion and ensure compliance of protocol.”
Dr. Miller reported that he has received payments from the Coventus Professional Liability Insurance: Risk Management Committee and the New Jersey Board of Medical Examiners. The other authors reported no relevant conflicts of interest. Dr. Krishna reported no relevant conflicts of interest.
SOURCE: Mullman L et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004023.
FROM OBSTETRICS & GYNECOLOGY
How ObGyns can best work with radiologists to optimize screening for patients with dense breasts
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
If your ObGyn practices are anything like ours, every time there is news coverage of a study regarding mammography or about efforts to pass a breast density inform law, your phone rings with patient calls. In fact, every density inform law enacted in the United States, except for in Illinois, directs patients to their referring provider—generally their ObGyn—to discuss the screening and risk implications of dense breast tissue.
The steady increased awareness of breast density means that we, as ObGyns and other primary care providers (PCPs), have additional responsibilities in managing the breast health of our patients. This includes guiding discussions with patients about what breast density means and whether supplemental screening beyond mammography might be beneficial.
As members of the Medical Advisory Board for DenseBreast-info.org (an online educational resource dedicated to providing breast density information to patients and health care professionals), we are aware of the growing body of evidence demonstrating improved detection of early breast cancer using supplemental screening in dense breasts. However, we know that there is confusion among clinicians about how and when to facilitate tailored screening for women with dense breasts or other breast cancer risk factors. Here we answer 6 questions focusing on how to navigate patient discussions around the topic and the best way to collaborate with radiologists to improve breast care for patients.
Play an active role
1. What role should ObGyns and PCPs play in women’s breast health?
Elizabeth Etkin-Kramer, MD: I am a firm believer that ObGyns and all women’s health providers should be able to assess their patients’ risk of breast cancer and explain the process for managing this risk with their patients. This explanation includes the clinical implications of breast density and when supplemental screening should be employed. It is also important for providers to know when to offer genetic testing and when a patient’s personal or family history indicates supplemental screening with breast magnetic resonance imaging (MRI).
DaCarla M. Albright, MD: I absolutely agree that PCPs, ObGyns, and family practitioners should spend the time to be educated about breast density and supplemental screening options. While the exact role providers play in managing patients’ breast health may vary depending on the practice type or location, the need for knowledge and comfort when talking with patients to help them make informed decisions is critical. Breast health and screening, including the importance of breast density, happen to be a particular interest of mine. I have participated in educational webinars, invited lectures, and breast cancer awareness media events on this topic in the past.
Continue to: Join forces with imaging centers...
Join forces with imaging centers
2. How can ObGyns and radiologists collaborate most effectively to use screening results to personalize breast care for patients?
Dr. Etkin-Kramer: It is important to have a close relationship with the radiologists that read our patients’ mammograms. We need to be able to easily contact the radiologist and quickly get clarification on a patient’s report or discuss next steps. Imaging centers should consider running outreach programs to educate their referring providers on how to risk assess, with this assessment inclusive of breast density. Dinner lectures or grand round meetings are effective to facilitate communication between the radiology community and the ObGyn community. Finally, as we all know, supplemental screening is often subject to copays and deductibles per insurance coverage. If advocacy groups, who are working to eliminate these types of costs, cannot get insurers to waive these payments, we need a less expensive self-pay option.
Dr. Albright: I definitely have and encourage an open line of communication between my practice and breast radiology, as well as our breast surgeons and cancer center to set up consultations as needed. We also invite our radiologists as guests to monthly practice meetings or grand rounds within our department to further improve access and open communication, as this environment is one in which greater provider education on density and adjunctive screening can be achieved.
Know when to refer a high-risk patient
3. Most ObGyns routinely collect family history and perform formal risk assessment. What do you need to know about referring patients to a high-risk program?
Dr. Etkin-Kramer: It is important as ObGyns to be knowledgeable about breast and ovarian cancer risk assessment and genetic testing for cancer susceptibility genes. Our patients expect that of us. I am comfortable doing risk assessment in my office, but I sometimes refer to other specialists in the community if the patient needs additional counseling. For risk assessment, I look at family and personal history, breast density, and other factors that might lead me to believe the patient might carry a hereditary cancer susceptibility gene, including Ashkenazi Jewish ancestry.1 When indicated, I check lifetime as well as short-term (5- to 10-year) risk, usually using Breast Cancer Surveillance Consortium (BCSC) or Tyrer-Cuzick/International Breast Cancer Intervention Study (IBIS) models, as these include breast density.
I discuss risk-reducing medications. The US Preventive Services Task Force recommends these agents if my patient’s 5-year risk of breast cancer is 1.67% or greater, and I strongly recommend chemoprevention when the patient’s 5-year BCSC risk exceeds 3%, provided likely benefits exceed risks.2,3 I discuss adding screening breast MRI if lifetime risk by Tyrer-Cuzick exceeds 20%. (Note that Gail and BCSC models are not recommended to be used to determine risk for purposes of supplemental screening with MRI as they do not consider paternal family history nor age of relatives at diagnosis.)
Dr. Albright: ObGyns should be able to ascertain a pertinent history and identify patients at risk for breast cancer based on their personal history, family history, and breast imaging/biopsy history, if relevant. We also need to improve our discussions of supplemental screening for patients who have heterogeneously dense or extremely dense breast tissue. I sense that some ObGyns may rely heavily on the radiologist to suggest supplemental screening, but patients actually look to ObGyns as their providers to have this knowledge and give them direction.
Since I practice at a large academic medical center, I have the opportunity to refer patients to our Breast Cancer Genetics Program because I may be limited on time for counseling in the office and do not want to miss salient details. With all of the information I have ascertained about the patient, I am able to determine and encourage appropriate screening and assure insurance coverage for adjunctive breast MRI when appropriate.
Continue to: Consider how you order patients’ screening to reduce barriers and cost...
Consider how you order patients’ screening to reduce barriers and cost
4. How would you suggest reducing barriers when referring patients for supplemental screening, such as MRI for high-risk women or ultrasound for those with dense breasts? Would you prefer it if such screening could be performed without additional script/referral? How does insurance coverage factor in?
Dr. Etkin-Kramer: I would love for a screening mammogram with possible ultrasound, on one script, to be the norm. One of the centers that I work with accepts a script written this way. Further, when a patient receives screening at a freestanding facility as opposed to a hospital, the fee for the supplemental screening may be lower because they do not add on a facility fee.
Dr. Albright: We have an order in our electronic health record that allows for screening mammography but adds on diagnostic mammography/bilateral ultrasonography, if indicated by imaging. I am mostly ordering that option now for all of my screening patients; rarely have I had issues with insurance accepting that script. As for when ordering an MRI, I always try to ensure that I have done the patient’s personal risk assessment and included that lifetime breast cancer risk on the order. If the risk is 20% or higher, I typically do not have any insurance coverage issues. If I am ordering MRI as supplemental screening, I typically order the “Fast MRI” protocol that our center offers. This order incurs a $299 out-of-pocket cost for the patient. Any patient with heterogeneously or extremely dense breasts on mammography should have this option, but it requires patient education, discussion with the provider, and an additional cost. I definitely think that insurers need to consider covering supplemental screening, since breast density is reportable in a majority of the US states and will soon be the national standard.
Pearls for guiding patients
5. How do you discuss breast density and the need for supplemental screening with your patients?
Dr. Etkin-Kramer: I strongly feel that my patients need to know when a screening test has limited ability to do its job. This is the case with dense breasts. Visuals help; when discussing breast density, I like the images supplied by DenseBreast-info.org (FIGURE). I explain the two implications of dense tissue:
- First, dense tissue makes it harder to visualize cancers in the breast—the denser the breasts, the less likely the radiologist can pick up a cancer, so mammographic sensitivity for extremely dense breasts can be as low as 25% to 50%.
- Second, high breast density adds to the risk of developing breast cancer. I explain that supplemental screening will pick up additional cancers in women with dense breasts. For example, breast ultrasound will pick up about 2-3/1000 additional breast cancers per year and MRI or molecular breast imaging (MBI) will pick up much more, perhaps 10/1000.
MRI is more invasive than an ultrasound and uses gadolinium, and MBI has more radiation. Supplemental screening is not endorsed by ACOG’s most recent Committee Opinion from 2017; 4 however, patients may choose to have it done. This is where shared-decision making is important.
I strongly recommend that all women’s health care providers complete the CME course on the DenseBreast-info.org website. “ Breast Density: Why It Matters ” is a certified educational program for referring physicians that helps health care professionals learn about breast density, its associated risks, and how best to guide patients regarding breast cancer screening.
Continue to: Dr. Albright...
Dr. Albright: When I discuss breast density, I make sure that patients understand that their mammogram determines the density of their breast tissue. I review that in the higher density categories (heterogeneously dense or extremely dense), there is a higher risk of missing cancer, and that these categories are also associated with a higher risk of breast cancer. I also discuss the potential need for supplemental screening, for which my institution primarily offers Fast MRI. However, we can offer breast ultrasonography instead as an option, especially for those concerned about gadolinium exposure. Our center offers either of these supplemental screenings at a cost of $299. I also review the lack of coverage for supplemental screening by some insurance carriers, as both providers and patients may need to advocate for insurer coverage of adjunct studies.
Educational resources
6. What reference materials, illustrations, or other tools do you use to educate your patients?
Dr. Etkin-Kramer: I frequently use handouts printed from the DenseBreast-info.org website, and there is now a brand new patient fact sheet that I have just started using. I also have an example of breast density categories from fatty replaced to extremely dense on my computer, and I am putting it on a new smart board.
Dr. Albright: The extensive resources available at DenseBreast-info.org can improve both patient and provider knowledge of these important issues, so I suggest patients visit that website, and I use many of the images and visuals to help explain breast density. I even use the materials from the website for educating my resident trainees on breast health and screening. ●
Nearly 16,000 children (up to age 19 years) face cancer-related treatment every year.1 For girls and young women, undergoing chest radiotherapy puts them at higher risk for secondary breast cancer. In fact, they have a 30% chance of developing such cancer by age 50—a risk that is similar to women with a BRCA1 mutation.2 Therefore, current recommendations for breast cancer screening among those who have undergone childhood chest radiation (≥20 Gy) are to begin annual mammography, with adjunct magnetic resonance imaging (MRI), at age 25 years (or 8 years after chest radiotherapy).3
To determine the benefits and risks of these recommendations, as well as of similar strategies, Yeh and colleagues performed simulation modeling using data from the Childhood Cancer Survivor Study and two CISNET (Cancer Intervention and Surveillance Modeling Network) models.4 For their study they targeted a cohort of female childhood cancer survivors having undergone chest radiotherapy and evaluated breast cancer screening with the following strategies:
- mammography plus MRI, starting at ages 25, 30, or 35 years and continuing to age 74
- MRI alone, starting at ages 25, 30, or 35 years and continuing to age 74.
They found that both strategies reduced the risk of breast cancer in the targeted cohort but that screening beginning at the earliest ages prevented most deaths. No screening at all was associated with a 10% to 11% lifetime risk of breast cancer, but mammography plus MRI beginning at age 25 reduced that risk by 56% to 71% depending on the model. Screening with MRI alone reduced mortality risk by 56% to 62%. When considering cost per quality adjusted life-year gained, the researchers found that screening beginning at age 30 to be the most cost-effective.4
Yeh and colleagues addressed concerns with mammography and radiation. Although they said the associated amount of radiation exposure is small, the use of mammography in women younger than age 30 is controversial—and not recommended by the American Cancer Society or the National Comprehensive Cancer Network.5,6
Bottom line. Yeh and colleagues conclude that MRI screening, with or without mammography, beginning between the ages of 25 and 30 should be emphasized in screening guidelines. They note the importance of insurance coverage for MRI in those at risk for breast cancer due to childhood radiation exposure.4
References
- National Cancer Institute. How common is cancer in children? https://www.cancer.gov/types/childhood-cancers/child-adolescentcancers-fact-sheet#how-common-is-cancer-in-children. Accessed September 25, 2020.
- Moskowitz CS, Chou JF, Wolden SL, et al. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217- 2223.
- Children’s Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. http:// www.survivorshipguidelines.org/pdf/2018/COG_LTFU_Guidelines_v5.pdf. Accessed September 25, 2020.
- Yeh JM, Lowry KP, Schechter CB, et al. Clinical benefits, harms, and cost-effectiveness of breast cancer screening for survivors of childhood cancer treated with chest radiation. Ann Intern Med. 2020;173:331-341.
- Saslow D, Boetes C, Burke W, et al; American Cancer Society Breast Cancer Advisory Group. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Breast cancer screening and diagnosis version 1.2019. https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed September 25, 2020.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
- Bharucha PP, Chiu KE, Francois FM, et al. Genetic testing and screening recommendations for patients with hereditary breast cancer. RadioGraphics. 2020;40:913-936.
- Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. 2011;29:2327-2333.
- Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22:3230-3235.
- American College of Obstetricians and Gynecologists. Committee opinion no. 625: management of women with dense breasts diagnosed by mammography [published correction appears in Obstet Gynecol. 2016;127:166]. Obstet Gynecol. 2015;125(3):750-751.
