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Time for another cup of coffee … or two
Nutrition enthusiasts have been saying for years that “we are what we eat.” In this issue of JFP, Drs. Malone and Tsai review the evidence regarding the medicinal properties of certain herbal and botanical supplements. (See here.) Although there are many unfounded claims about the health effects of a wide variety of supplements, increasing evidence from well-conducted randomized trials and large epidemiologic studies demonstrates that certain items we ingest have therapeutic value for a variety of conditions.
However, as Dr. Malone points out, herbal supplements and botanicals are not regulated by the US Food and Drug Administration, so manufacturers are not required to provide proof of effectiveness or safety to market their products. Some of these products have adverse effects. For example, butterbur can cause liver toxicity.1
Because about 38% of Americans use supplements, all primary care clinicians should know which products do—and do not—have evidence of efficacy.2 I suggest you read Dr. Malone’s 2-part article (part 2 is available here), but I can’t resist highlighting several of my favorites:
Coffee. Coffee used to be maligned because of its caffeine content, but more recent evidence suggests it protects against liver disease and has positive effects on cardiovascular disease and even mortality. (See Dr. Malone’s article for references.) There are no randomized trials, however, so we can’t be entirely sure if these associations are causal, but at least I can feel better about the 4 cups of coffee I drink every day!
Tea, especially green tea, appears to have many positive effects on health, including potential roles in reducing the risk of cancer, cardiovascular disease, type 2 diabetes, and even dementia. As with coffee, these associations are based on large observational studies and not randomized trials.
Chamomile. If your coffee gives you too much of a buzz and causes you to feel anxious, calm down with chamomile tea or oil. Evidence from randomized trials indicates it has positive effects on insomnia and anxiety.
Peppermint oil. The data for calming irritable bowel syndrome is fairly strong, and it may be effective in aborting migraines when applied to the forehead. It’s certainly worth a try for these difficult-to-treat conditions.
When patients ask you about botanicals and herbals, a great resource is
Now I will finish my fourth cup of coffee . . .
1. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
2. National Center for Complementary and Integrative Health. The use of complementary and alternative medicine in the United States. Available at: https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Accessed December 14, 2017.
Editor-in-Chief
Editor-in-Chief
Editor-in-Chief
Nutrition enthusiasts have been saying for years that “we are what we eat.” In this issue of JFP, Drs. Malone and Tsai review the evidence regarding the medicinal properties of certain herbal and botanical supplements. (See here.) Although there are many unfounded claims about the health effects of a wide variety of supplements, increasing evidence from well-conducted randomized trials and large epidemiologic studies demonstrates that certain items we ingest have therapeutic value for a variety of conditions.
However, as Dr. Malone points out, herbal supplements and botanicals are not regulated by the US Food and Drug Administration, so manufacturers are not required to provide proof of effectiveness or safety to market their products. Some of these products have adverse effects. For example, butterbur can cause liver toxicity.1
Because about 38% of Americans use supplements, all primary care clinicians should know which products do—and do not—have evidence of efficacy.2 I suggest you read Dr. Malone’s 2-part article (part 2 is available here), but I can’t resist highlighting several of my favorites:
Coffee. Coffee used to be maligned because of its caffeine content, but more recent evidence suggests it protects against liver disease and has positive effects on cardiovascular disease and even mortality. (See Dr. Malone’s article for references.) There are no randomized trials, however, so we can’t be entirely sure if these associations are causal, but at least I can feel better about the 4 cups of coffee I drink every day!
Tea, especially green tea, appears to have many positive effects on health, including potential roles in reducing the risk of cancer, cardiovascular disease, type 2 diabetes, and even dementia. As with coffee, these associations are based on large observational studies and not randomized trials.
Chamomile. If your coffee gives you too much of a buzz and causes you to feel anxious, calm down with chamomile tea or oil. Evidence from randomized trials indicates it has positive effects on insomnia and anxiety.
Peppermint oil. The data for calming irritable bowel syndrome is fairly strong, and it may be effective in aborting migraines when applied to the forehead. It’s certainly worth a try for these difficult-to-treat conditions.
When patients ask you about botanicals and herbals, a great resource is
Now I will finish my fourth cup of coffee . . .
Nutrition enthusiasts have been saying for years that “we are what we eat.” In this issue of JFP, Drs. Malone and Tsai review the evidence regarding the medicinal properties of certain herbal and botanical supplements. (See here.) Although there are many unfounded claims about the health effects of a wide variety of supplements, increasing evidence from well-conducted randomized trials and large epidemiologic studies demonstrates that certain items we ingest have therapeutic value for a variety of conditions.
However, as Dr. Malone points out, herbal supplements and botanicals are not regulated by the US Food and Drug Administration, so manufacturers are not required to provide proof of effectiveness or safety to market their products. Some of these products have adverse effects. For example, butterbur can cause liver toxicity.1
Because about 38% of Americans use supplements, all primary care clinicians should know which products do—and do not—have evidence of efficacy.2 I suggest you read Dr. Malone’s 2-part article (part 2 is available here), but I can’t resist highlighting several of my favorites:
Coffee. Coffee used to be maligned because of its caffeine content, but more recent evidence suggests it protects against liver disease and has positive effects on cardiovascular disease and even mortality. (See Dr. Malone’s article for references.) There are no randomized trials, however, so we can’t be entirely sure if these associations are causal, but at least I can feel better about the 4 cups of coffee I drink every day!
Tea, especially green tea, appears to have many positive effects on health, including potential roles in reducing the risk of cancer, cardiovascular disease, type 2 diabetes, and even dementia. As with coffee, these associations are based on large observational studies and not randomized trials.
Chamomile. If your coffee gives you too much of a buzz and causes you to feel anxious, calm down with chamomile tea or oil. Evidence from randomized trials indicates it has positive effects on insomnia and anxiety.
Peppermint oil. The data for calming irritable bowel syndrome is fairly strong, and it may be effective in aborting migraines when applied to the forehead. It’s certainly worth a try for these difficult-to-treat conditions.
When patients ask you about botanicals and herbals, a great resource is
Now I will finish my fourth cup of coffee . . .
1. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
2. National Center for Complementary and Integrative Health. The use of complementary and alternative medicine in the United States. Available at: https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Accessed December 14, 2017.
1. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
2. National Center for Complementary and Integrative Health. The use of complementary and alternative medicine in the United States. Available at: https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Accessed December 14, 2017.
Is this hypertension treatment strategy based on SOR “A” evidence?
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al gave an “A” Strength of Recommendation (SOR) rating to the Practice Recommendation that read: “Target a systolic blood pressure (SBP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden.”
As justification for this SBP target, the authors cited a subgroup analysis from the Systolic Blood Pressure Intervention Trial (SPRINT),1 which consisted of patients ≥75 years of age.2 I posit that the inconsistencies of the data cited by Hansell et al contradict an “A” rating, and that the methodology used in SPRINT greatly mitigates the generalizability of the results.
First, Hansell et al admit that no consensus exists on an optimal BP target for older patients. SOR taxonomy requires that the evidence behind an SOR of “A” be based on consistent and good-quality patient-oriented evidence.3 One source cited by the authors states that evidence supporting lower targets is inconsistent,4 while a recent Cochrane review does not support low BP targets.5 Given that the evidence is inconsistent, the SOR should be a “B”, at best.
Second, the evidence to target a systolic BP <120 mm Hg primarily comes from SPRINT.1,2,4 In a Letter to the Editor that appeared in The New England Journal of Medicine, Dr. Marc A. Pfeffer addressed a key methodology issue of that trial: SPRINT protocol called for the withdrawal of antihypertensive therapy in the standard treatment group if a single systolic BP reading was <130 mm Hg, or if readings at 2 or more consecutive visits were <135 mm Hg, regardless of patient symptoms.6
The letter also questioned how frequently this withdrawal occurred, to which the SPRINT authors replied that 87% of participants required at least one reduction in the dose of medication to maintain the treatment target in the standard group, and complete withdrawal of medication was required in <7.5% of participants.7 While this dose adjustment may have been necessary to adequately test the SPRINT hypothesis that lower systolic BP targets are better, routine dose reduction in an asymptomatic patient is not standard practice.
Given the small benefit in absolute risk reduction in SPRINT’s aggressive hypertensive treatment arm of 0.54% per year for the primary composite outcome and 0.37% per year for all-cause mortality,2 the frequent medication dose reductions in the standard treatment arm likely contributed significantly to the statistical benefit seen in the aggressive treatment group in SPRINT.
If an SOR of “A” for BP targets is to be made, the print publication of Hansell et al’s article should communicate the degree of benefit, preferably in terms of absolute risk reduction. Only the online publication of TABLE W1 stated the degree of benefit in the SPRINT subgroup study, but it was stated in terms of relative risk.
Given the current suboptimal rates of hypertension control, primary care physicians would do well to impact morbidity and mortality in older adults by working to achieve standard targets, such as an SBP of <140 mm Hg or <150 mm Hg. Once standard targets are achieved, a conversation could then ensue about the potential benefits and harms of lower BP targets.
Chris Fallert, MD
St. Paul, Minn
1. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
2. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
3. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
4. Weiss J, Freeman M, Low A, et al. Benefits and harms of intensive blood pressure treatment in adults aged 60 years or older: a systematic review and meta-analysis. Ann Intern Med. 2017;166:419-429.
5. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
6. Pfeffer MA. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2290.
7. Wright JT Jr, Whelton PK, Reboussin DM. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2294.
Authors’ response:
An SOR of “A” is based on consistent and good-quality patient-oriented evidence, which is further defined for treatment, prevention, and screening studies as (a) systematic reviews/meta-analyses of randomized controlled trials (RCTs) with consistent findings or (b) a high-quality individual RCT.1 The recommendation to “target a systolic blood pressure (BP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden” meets level 1 evidence based on both (a) and (b).
While a Cochrane review of hypertension did not support a systolic BP target <120 mm Hg, the populations evaluated included a variety of ages; the studies did not specifically focus on those ≥75 years of age with inherently high cardiovascular risk while excluding patients with diabetes.2 The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial results,3 which are often viewed as inconsistent with SPRINT,4 included patients with diabetes and patients of a younger average age than SPRINT. Although no overall mortality benefit of intensive BP control was found in the ACCORD trial, there was significant reduction in stroke, as well as additional benefit in the ACCORD standard glycemia group.3,5
The American College of Cardiology/American Heart Association 2017 BP guidelines summarize several meta-analyses that consistently support tighter BP control with recommendations for a lower BP target of <130 mm Hg systolic.5,6 They selected a target of <130 mm Hg, rather than <120 mm Hg, assuming that general health care providers cannot be as efficacious at lowering BP as researchers in efficacy trials.5
With regard to medication withdrawal as a flaw in the SPRINT design,4 an accepted geriatric principle is reduction in polypharmacy whenever possible. Medication reduction or withdrawal when a patient is too far below target is prudent. The 2 different target groups in an RCT have to be statistically different to draw conclusions about the differences. This strategy has been employed in other BP trials. Medication withdrawal is an appropriate means to achieve targets, which the SPRINT investigators did successfully with a least-square mean systolic BP for patients ≥75 years of age in the control group of 134.8 mm Hg and 123.4 mm Hg in the intensive group.4 Even with reduction in polypharmacy in the standard group, SPRINT demonstrated cardiovascular and mortality benefit with tighter control.4
With regard to Dr. Fallert’s comments about a small absolute risk reduction for the entire SPRINT study population, our article in JFP specifically pertains to adults ≥75 years of age. The numbers needed to treat for composite cardiovascular outcomes and all-cause mortality in the ≥75 SPRINT group are 27 (95% confidence interval [CI], 19-61) and 41 (95% CI, 27-145), respectively.4
We agree that there is suboptimal hypertension control at present. However, physicians should not only focus on this modifiable risk factor to reduce CVD risk and mortality in appropriate patients, but they should focus on doing it to the evidence-based goal.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
2. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
3. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
4. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
5. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
6. Reboussin DM, Allen NB, Griswold ME, et al. Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Available at: http://hyper.ahajournals.org/content/early/2017/11/10/HYP.0000000000000067. Accessed December 12, 2017.
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al gave an “A” Strength of Recommendation (SOR) rating to the Practice Recommendation that read: “Target a systolic blood pressure (SBP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden.”
As justification for this SBP target, the authors cited a subgroup analysis from the Systolic Blood Pressure Intervention Trial (SPRINT),1 which consisted of patients ≥75 years of age.2 I posit that the inconsistencies of the data cited by Hansell et al contradict an “A” rating, and that the methodology used in SPRINT greatly mitigates the generalizability of the results.
First, Hansell et al admit that no consensus exists on an optimal BP target for older patients. SOR taxonomy requires that the evidence behind an SOR of “A” be based on consistent and good-quality patient-oriented evidence.3 One source cited by the authors states that evidence supporting lower targets is inconsistent,4 while a recent Cochrane review does not support low BP targets.5 Given that the evidence is inconsistent, the SOR should be a “B”, at best.
Second, the evidence to target a systolic BP <120 mm Hg primarily comes from SPRINT.1,2,4 In a Letter to the Editor that appeared in The New England Journal of Medicine, Dr. Marc A. Pfeffer addressed a key methodology issue of that trial: SPRINT protocol called for the withdrawal of antihypertensive therapy in the standard treatment group if a single systolic BP reading was <130 mm Hg, or if readings at 2 or more consecutive visits were <135 mm Hg, regardless of patient symptoms.6
The letter also questioned how frequently this withdrawal occurred, to which the SPRINT authors replied that 87% of participants required at least one reduction in the dose of medication to maintain the treatment target in the standard group, and complete withdrawal of medication was required in <7.5% of participants.7 While this dose adjustment may have been necessary to adequately test the SPRINT hypothesis that lower systolic BP targets are better, routine dose reduction in an asymptomatic patient is not standard practice.
Given the small benefit in absolute risk reduction in SPRINT’s aggressive hypertensive treatment arm of 0.54% per year for the primary composite outcome and 0.37% per year for all-cause mortality,2 the frequent medication dose reductions in the standard treatment arm likely contributed significantly to the statistical benefit seen in the aggressive treatment group in SPRINT.
If an SOR of “A” for BP targets is to be made, the print publication of Hansell et al’s article should communicate the degree of benefit, preferably in terms of absolute risk reduction. Only the online publication of TABLE W1 stated the degree of benefit in the SPRINT subgroup study, but it was stated in terms of relative risk.
Given the current suboptimal rates of hypertension control, primary care physicians would do well to impact morbidity and mortality in older adults by working to achieve standard targets, such as an SBP of <140 mm Hg or <150 mm Hg. Once standard targets are achieved, a conversation could then ensue about the potential benefits and harms of lower BP targets.
Chris Fallert, MD
St. Paul, Minn
1. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
2. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
3. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
4. Weiss J, Freeman M, Low A, et al. Benefits and harms of intensive blood pressure treatment in adults aged 60 years or older: a systematic review and meta-analysis. Ann Intern Med. 2017;166:419-429.
5. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
6. Pfeffer MA. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2290.
7. Wright JT Jr, Whelton PK, Reboussin DM. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2294.
Authors’ response:
An SOR of “A” is based on consistent and good-quality patient-oriented evidence, which is further defined for treatment, prevention, and screening studies as (a) systematic reviews/meta-analyses of randomized controlled trials (RCTs) with consistent findings or (b) a high-quality individual RCT.1 The recommendation to “target a systolic blood pressure (BP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden” meets level 1 evidence based on both (a) and (b).
While a Cochrane review of hypertension did not support a systolic BP target <120 mm Hg, the populations evaluated included a variety of ages; the studies did not specifically focus on those ≥75 years of age with inherently high cardiovascular risk while excluding patients with diabetes.2 The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial results,3 which are often viewed as inconsistent with SPRINT,4 included patients with diabetes and patients of a younger average age than SPRINT. Although no overall mortality benefit of intensive BP control was found in the ACCORD trial, there was significant reduction in stroke, as well as additional benefit in the ACCORD standard glycemia group.3,5
The American College of Cardiology/American Heart Association 2017 BP guidelines summarize several meta-analyses that consistently support tighter BP control with recommendations for a lower BP target of <130 mm Hg systolic.5,6 They selected a target of <130 mm Hg, rather than <120 mm Hg, assuming that general health care providers cannot be as efficacious at lowering BP as researchers in efficacy trials.5
With regard to medication withdrawal as a flaw in the SPRINT design,4 an accepted geriatric principle is reduction in polypharmacy whenever possible. Medication reduction or withdrawal when a patient is too far below target is prudent. The 2 different target groups in an RCT have to be statistically different to draw conclusions about the differences. This strategy has been employed in other BP trials. Medication withdrawal is an appropriate means to achieve targets, which the SPRINT investigators did successfully with a least-square mean systolic BP for patients ≥75 years of age in the control group of 134.8 mm Hg and 123.4 mm Hg in the intensive group.4 Even with reduction in polypharmacy in the standard group, SPRINT demonstrated cardiovascular and mortality benefit with tighter control.4
With regard to Dr. Fallert’s comments about a small absolute risk reduction for the entire SPRINT study population, our article in JFP specifically pertains to adults ≥75 years of age. The numbers needed to treat for composite cardiovascular outcomes and all-cause mortality in the ≥75 SPRINT group are 27 (95% confidence interval [CI], 19-61) and 41 (95% CI, 27-145), respectively.4
We agree that there is suboptimal hypertension control at present. However, physicians should not only focus on this modifiable risk factor to reduce CVD risk and mortality in appropriate patients, but they should focus on doing it to the evidence-based goal.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
2. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
3. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
4. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
5. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
6. Reboussin DM, Allen NB, Griswold ME, et al. Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Available at: http://hyper.ahajournals.org/content/early/2017/11/10/HYP.0000000000000067. Accessed December 12, 2017.
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al gave an “A” Strength of Recommendation (SOR) rating to the Practice Recommendation that read: “Target a systolic blood pressure (SBP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden.”
As justification for this SBP target, the authors cited a subgroup analysis from the Systolic Blood Pressure Intervention Trial (SPRINT),1 which consisted of patients ≥75 years of age.2 I posit that the inconsistencies of the data cited by Hansell et al contradict an “A” rating, and that the methodology used in SPRINT greatly mitigates the generalizability of the results.
First, Hansell et al admit that no consensus exists on an optimal BP target for older patients. SOR taxonomy requires that the evidence behind an SOR of “A” be based on consistent and good-quality patient-oriented evidence.3 One source cited by the authors states that evidence supporting lower targets is inconsistent,4 while a recent Cochrane review does not support low BP targets.5 Given that the evidence is inconsistent, the SOR should be a “B”, at best.
Second, the evidence to target a systolic BP <120 mm Hg primarily comes from SPRINT.1,2,4 In a Letter to the Editor that appeared in The New England Journal of Medicine, Dr. Marc A. Pfeffer addressed a key methodology issue of that trial: SPRINT protocol called for the withdrawal of antihypertensive therapy in the standard treatment group if a single systolic BP reading was <130 mm Hg, or if readings at 2 or more consecutive visits were <135 mm Hg, regardless of patient symptoms.6
The letter also questioned how frequently this withdrawal occurred, to which the SPRINT authors replied that 87% of participants required at least one reduction in the dose of medication to maintain the treatment target in the standard group, and complete withdrawal of medication was required in <7.5% of participants.7 While this dose adjustment may have been necessary to adequately test the SPRINT hypothesis that lower systolic BP targets are better, routine dose reduction in an asymptomatic patient is not standard practice.
Given the small benefit in absolute risk reduction in SPRINT’s aggressive hypertensive treatment arm of 0.54% per year for the primary composite outcome and 0.37% per year for all-cause mortality,2 the frequent medication dose reductions in the standard treatment arm likely contributed significantly to the statistical benefit seen in the aggressive treatment group in SPRINT.
If an SOR of “A” for BP targets is to be made, the print publication of Hansell et al’s article should communicate the degree of benefit, preferably in terms of absolute risk reduction. Only the online publication of TABLE W1 stated the degree of benefit in the SPRINT subgroup study, but it was stated in terms of relative risk.
Given the current suboptimal rates of hypertension control, primary care physicians would do well to impact morbidity and mortality in older adults by working to achieve standard targets, such as an SBP of <140 mm Hg or <150 mm Hg. Once standard targets are achieved, a conversation could then ensue about the potential benefits and harms of lower BP targets.
Chris Fallert, MD
St. Paul, Minn
1. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
2. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
3. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
4. Weiss J, Freeman M, Low A, et al. Benefits and harms of intensive blood pressure treatment in adults aged 60 years or older: a systematic review and meta-analysis. Ann Intern Med. 2017;166:419-429.
5. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
6. Pfeffer MA. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2290.
7. Wright JT Jr, Whelton PK, Reboussin DM. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2016;374:2294.
Authors’ response:
An SOR of “A” is based on consistent and good-quality patient-oriented evidence, which is further defined for treatment, prevention, and screening studies as (a) systematic reviews/meta-analyses of randomized controlled trials (RCTs) with consistent findings or (b) a high-quality individual RCT.1 The recommendation to “target a systolic blood pressure (BP) <120 mm Hg in community-dwelling, nondiabetic patients ≥75 years of age if it is achievable without undue burden” meets level 1 evidence based on both (a) and (b).
While a Cochrane review of hypertension did not support a systolic BP target <120 mm Hg, the populations evaluated included a variety of ages; the studies did not specifically focus on those ≥75 years of age with inherently high cardiovascular risk while excluding patients with diabetes.2 The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial results,3 which are often viewed as inconsistent with SPRINT,4 included patients with diabetes and patients of a younger average age than SPRINT. Although no overall mortality benefit of intensive BP control was found in the ACCORD trial, there was significant reduction in stroke, as well as additional benefit in the ACCORD standard glycemia group.3,5
The American College of Cardiology/American Heart Association 2017 BP guidelines summarize several meta-analyses that consistently support tighter BP control with recommendations for a lower BP target of <130 mm Hg systolic.5,6 They selected a target of <130 mm Hg, rather than <120 mm Hg, assuming that general health care providers cannot be as efficacious at lowering BP as researchers in efficacy trials.5
With regard to medication withdrawal as a flaw in the SPRINT design,4 an accepted geriatric principle is reduction in polypharmacy whenever possible. Medication reduction or withdrawal when a patient is too far below target is prudent. The 2 different target groups in an RCT have to be statistically different to draw conclusions about the differences. This strategy has been employed in other BP trials. Medication withdrawal is an appropriate means to achieve targets, which the SPRINT investigators did successfully with a least-square mean systolic BP for patients ≥75 years of age in the control group of 134.8 mm Hg and 123.4 mm Hg in the intensive group.4 Even with reduction in polypharmacy in the standard group, SPRINT demonstrated cardiovascular and mortality benefit with tighter control.4
With regard to Dr. Fallert’s comments about a small absolute risk reduction for the entire SPRINT study population, our article in JFP specifically pertains to adults ≥75 years of age. The numbers needed to treat for composite cardiovascular outcomes and all-cause mortality in the ≥75 SPRINT group are 27 (95% confidence interval [CI], 19-61) and 41 (95% CI, 27-145), respectively.4
We agree that there is suboptimal hypertension control at present. However, physicians should not only focus on this modifiable risk factor to reduce CVD risk and mortality in appropriate patients, but they should focus on doing it to the evidence-based goal.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69:548-556.
2. Garrison SR, Kolber MR, Korownyk CS, et al. Blood pressure targets for hypertension in older adults. Cochrane Database Syst Rev. 2017;8:CD011575.
3. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
4. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
5. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
6. Reboussin DM, Allen NB, Griswold ME, et al. Systematic Review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. Available at: http://hyper.ahajournals.org/content/early/2017/11/10/HYP.0000000000000067. Accessed December 12, 2017.
Let’s recognize Dr. John Geyman, too
Thank you for your tribute to David Warfield Stires, The Journal of Family Practice’s founding publisher (J Fam Pract. 2017;66:654-655). The real hero of the story, however, is Dr. John Geyman, who had the vision to found a research journal at the birth of our specialty. This was no easy task, as John faced a challenging chicken-and-egg problem: how to establish a research journal when academic family medicine was just getting underway and had no track record of generating a steady stream of quality research. The latter problem was due, in part, to the lack of a research journal devoted to promoting and publishing research in the field.
Yet, John did it, putting family medicine research on the publishing map. His groundbreaking work set the stage for future journals, including the Journal of the American Board of Family Medicine, the American Medical Association’s now-defunct Archives of Family Medicine, and the American Academy of Family Physicians’ Annals of Family Medicine.
As a family medicine resident in the 1970s, I remember coveting JFP so much that I managed to collect every issue from Volume 1, Issue 1, through the turn of the century. And as a young faculty member at Georgetown University Medical Center in the 1980s, I painstakingly created an annotated bibliography of the then-published content of JFP to use for teaching, research, and administration.
When I became editor of American Family Physician in 1988, I made a pilgrimage to the University of Washington School of Medicine in Seattle, where John was chairman of the Department of Family Medicine. I wanted to seek his advice, learn from his vast experience, and pay tribute to all that he’d done for our specialty. Over the past 30 years, John has continued to leave his mark. (See http://www.johngeymanmd.org/bio.html.)
A tribute to David Warfield Stires is incomplete without a corresponding acknowledgement and celebration of John’s decades-long visionary leadership in family medicine.
Jay Siwek, MD
Washington, DC
Thank you for your tribute to David Warfield Stires, The Journal of Family Practice’s founding publisher (J Fam Pract. 2017;66:654-655). The real hero of the story, however, is Dr. John Geyman, who had the vision to found a research journal at the birth of our specialty. This was no easy task, as John faced a challenging chicken-and-egg problem: how to establish a research journal when academic family medicine was just getting underway and had no track record of generating a steady stream of quality research. The latter problem was due, in part, to the lack of a research journal devoted to promoting and publishing research in the field.
Yet, John did it, putting family medicine research on the publishing map. His groundbreaking work set the stage for future journals, including the Journal of the American Board of Family Medicine, the American Medical Association’s now-defunct Archives of Family Medicine, and the American Academy of Family Physicians’ Annals of Family Medicine.
As a family medicine resident in the 1970s, I remember coveting JFP so much that I managed to collect every issue from Volume 1, Issue 1, through the turn of the century. And as a young faculty member at Georgetown University Medical Center in the 1980s, I painstakingly created an annotated bibliography of the then-published content of JFP to use for teaching, research, and administration.
When I became editor of American Family Physician in 1988, I made a pilgrimage to the University of Washington School of Medicine in Seattle, where John was chairman of the Department of Family Medicine. I wanted to seek his advice, learn from his vast experience, and pay tribute to all that he’d done for our specialty. Over the past 30 years, John has continued to leave his mark. (See http://www.johngeymanmd.org/bio.html.)
A tribute to David Warfield Stires is incomplete without a corresponding acknowledgement and celebration of John’s decades-long visionary leadership in family medicine.
Jay Siwek, MD
Washington, DC
Thank you for your tribute to David Warfield Stires, The Journal of Family Practice’s founding publisher (J Fam Pract. 2017;66:654-655). The real hero of the story, however, is Dr. John Geyman, who had the vision to found a research journal at the birth of our specialty. This was no easy task, as John faced a challenging chicken-and-egg problem: how to establish a research journal when academic family medicine was just getting underway and had no track record of generating a steady stream of quality research. The latter problem was due, in part, to the lack of a research journal devoted to promoting and publishing research in the field.
Yet, John did it, putting family medicine research on the publishing map. His groundbreaking work set the stage for future journals, including the Journal of the American Board of Family Medicine, the American Medical Association’s now-defunct Archives of Family Medicine, and the American Academy of Family Physicians’ Annals of Family Medicine.
As a family medicine resident in the 1970s, I remember coveting JFP so much that I managed to collect every issue from Volume 1, Issue 1, through the turn of the century. And as a young faculty member at Georgetown University Medical Center in the 1980s, I painstakingly created an annotated bibliography of the then-published content of JFP to use for teaching, research, and administration.
When I became editor of American Family Physician in 1988, I made a pilgrimage to the University of Washington School of Medicine in Seattle, where John was chairman of the Department of Family Medicine. I wanted to seek his advice, learn from his vast experience, and pay tribute to all that he’d done for our specialty. Over the past 30 years, John has continued to leave his mark. (See http://www.johngeymanmd.org/bio.html.)
A tribute to David Warfield Stires is incomplete without a corresponding acknowledgement and celebration of John’s decades-long visionary leadership in family medicine.
Jay Siwek, MD
Washington, DC
Utilize guidelines, but customize BP treatment in older patients
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al recommend a systolic blood pressure (SBP) treatment target of <120 mm Hg for community-dwelling, nondiabetic patients ≥75 years of age. This recommendation is not supported by the authors’ cited guidelines, and we have serious concerns about the risk of harm from such overly stringent BP control in this population.
While Hansell et al acknowledge that no consensus exists regarding an optimal BP target for older patients, the authors cite the Eighth Joint National Committee (JNC 8), the American College of Physicians (ACP), the Systolic Blood Pressure Intervention Trial (SPRINT) subgroup analysis, and the BP arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to justify their recommendation. But as the authors mention, JNC 8 conducted a comprehensive review of the available evidence and determined that a BP target of <150/90 mm Hg for hypertensive patients ≥60 years of age is appropriate.1
The authors also state that ACP recommends an SBP target of <140 mm Hg, while, in fact, the recommendations from ACP (which are joint guidelines published with the American Academy of Family Physicians) say that high-quality evidence strongly supports an SBP target of <150 mm Hg to reduce the risk for mortality, stroke, and cardiac events in adults ≥60 years of age.2
SPRINT does support Hansell et al’s recommended SBP target of <120 mm Hg, but this trial provided only composite data of adults ≥75 years of age and did not differentiate between the outcomes in otherwise healthy adults ≥75 years of age vs those with cardiovascular conditions.3 As Hansell et al point out, the SPRINT trial was halted prematurely, which compromises the validity of their findings.
Lastly, the ACCORD trial did not find benefit to treating SBP <120 mm Hg compared with <140 mm Hg in adults with diabetes, but it did find substantial harms in the <120 mm Hg group, including an increased risk of renal impairment and hypokalemia.4
Hansel et al’s overreliance on the SPRINT subgroup analysis represents a significant flaw in the assertion that an SBP target <120 mm Hg is reasonable for all community-dwelling, non-diabetic adults ≥75 years of age. While the authors made the allowance that a higher target (<140 mm Hg) is acceptable if a target of <120 mm Hg places undue burden on the patient, the guidelines they cited, when considered together, suggest that starting at a higher target is not only sufficient to prevent complications, but also reduces overtreatment.
Adults ≥75 years of age are a diverse group regarding disease conditions, life expectancy, and personal priorities. While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines so that we can tailor BP treatment targets to each patient’s unique clinical situation and personal priorities. Applying a blanket recommendation to this heterogeneous population may result in significant harms from overtreatment.
Jennifer L. Middleton, MD, MPH, FAAFP; Miriam Chan, PharmD, CDE
Columbus, Ohio
1. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
2. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
3. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
4. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585.
Authors’ response:
We agree with the title of this letter, “Utilize guidelines, but customize BP treatment in older patients.” Our recommendations are not limited to targeting a systolic BP <120 mm Hg for community-dwelling, nondiabetic adults ≥75 years of age, but include consideration for “undue burden.” Our third practice recommendation, which recommends that one consider cognitive function, polypharmacy, multimorbidity, and frailty, is an equally—if not more—important recommendation.
With regard to the specific concerns about the current guidelines:
- The American College of Physicians and American Academy of Family Physicians’ “Recommendation 1” advocates a systolic BP goal <150 mm Hg for adults ≥60 years of age. However, “Recommendation 3” endorses intensifying treatment in adults ≥60 years of age at high cardiovascular (CV) risk. Based on Framingham criteria, all adults ≥75 years of age are considered at high risk for CV disease, as stated in our article. Therefore, “Recommendation 3” for a target of <140 mm Hg is applicable for the population addressed in our article.1
- The Eighth Joint National Committee (JNC 8) does recommend a BP target <150 mm Hg for adults ≥60 years of age, but does not take into account recent data, which is why we wanted to highlight that data for physicians.2
- Since submission of our article, The American College of Cardiology/American Heart Association (ACC/AHA) has published its first set of guidelines since 2003, which lowered BP target to <130 mm Hg in patients with high CV risk. Those guidelines outline the validity of SPRINT and the consistency of the existing evidence, including the linear relationship of BP and mortality.3
- SPRINT was halted early specifically because of the mortality benefit in the intensive treatment group, which is ethically appropriate.4 It is unclear to us how this compromises the validity of the trial. There is often concern for bias from early cessation in small trials, but this was a large, well-powered trial.
- The ACC/AHA guidelines also address some of the nuances of ACCORD, which is specific to patients with diabetes (whom we excluded from our first Practice Recommendation). Although no overall mortality benefit was found, there was stroke reduction in this group and additional benefit in the standard glycemia group.3,5 A meta-analysis of SPRINT and ACCORD showed CV disease reduction with a BP target <120 mm Hg.6
Although we do believe that SPRINT is a landmark trial contributing a great deal to our recommendations, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions. We stressed that prescribers use caution and slow titration because of adverse effects. Geriatric medicine is a complex art, and one of the goals of our article was to highlight this complexity and emphasize the importance of considering goals of care, comorbidity, frailty, and cognitive function when choosing optimal BP targets.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
2. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
3. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
4. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
5. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
6. Perkovic V, Rodgers A. Redefining blood-pressure targets—SPRINT starts the marathon. N Engl Med. 2015;373:2175-2178.
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al recommend a systolic blood pressure (SBP) treatment target of <120 mm Hg for community-dwelling, nondiabetic patients ≥75 years of age. This recommendation is not supported by the authors’ cited guidelines, and we have serious concerns about the risk of harm from such overly stringent BP control in this population.
While Hansell et al acknowledge that no consensus exists regarding an optimal BP target for older patients, the authors cite the Eighth Joint National Committee (JNC 8), the American College of Physicians (ACP), the Systolic Blood Pressure Intervention Trial (SPRINT) subgroup analysis, and the BP arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to justify their recommendation. But as the authors mention, JNC 8 conducted a comprehensive review of the available evidence and determined that a BP target of <150/90 mm Hg for hypertensive patients ≥60 years of age is appropriate.1
The authors also state that ACP recommends an SBP target of <140 mm Hg, while, in fact, the recommendations from ACP (which are joint guidelines published with the American Academy of Family Physicians) say that high-quality evidence strongly supports an SBP target of <150 mm Hg to reduce the risk for mortality, stroke, and cardiac events in adults ≥60 years of age.2
SPRINT does support Hansell et al’s recommended SBP target of <120 mm Hg, but this trial provided only composite data of adults ≥75 years of age and did not differentiate between the outcomes in otherwise healthy adults ≥75 years of age vs those with cardiovascular conditions.3 As Hansell et al point out, the SPRINT trial was halted prematurely, which compromises the validity of their findings.
Lastly, the ACCORD trial did not find benefit to treating SBP <120 mm Hg compared with <140 mm Hg in adults with diabetes, but it did find substantial harms in the <120 mm Hg group, including an increased risk of renal impairment and hypokalemia.4
Hansel et al’s overreliance on the SPRINT subgroup analysis represents a significant flaw in the assertion that an SBP target <120 mm Hg is reasonable for all community-dwelling, non-diabetic adults ≥75 years of age. While the authors made the allowance that a higher target (<140 mm Hg) is acceptable if a target of <120 mm Hg places undue burden on the patient, the guidelines they cited, when considered together, suggest that starting at a higher target is not only sufficient to prevent complications, but also reduces overtreatment.
Adults ≥75 years of age are a diverse group regarding disease conditions, life expectancy, and personal priorities. While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines so that we can tailor BP treatment targets to each patient’s unique clinical situation and personal priorities. Applying a blanket recommendation to this heterogeneous population may result in significant harms from overtreatment.
Jennifer L. Middleton, MD, MPH, FAAFP; Miriam Chan, PharmD, CDE
Columbus, Ohio
1. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
2. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
3. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
4. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585.
Authors’ response:
We agree with the title of this letter, “Utilize guidelines, but customize BP treatment in older patients.” Our recommendations are not limited to targeting a systolic BP <120 mm Hg for community-dwelling, nondiabetic adults ≥75 years of age, but include consideration for “undue burden.” Our third practice recommendation, which recommends that one consider cognitive function, polypharmacy, multimorbidity, and frailty, is an equally—if not more—important recommendation.
With regard to the specific concerns about the current guidelines:
- The American College of Physicians and American Academy of Family Physicians’ “Recommendation 1” advocates a systolic BP goal <150 mm Hg for adults ≥60 years of age. However, “Recommendation 3” endorses intensifying treatment in adults ≥60 years of age at high cardiovascular (CV) risk. Based on Framingham criteria, all adults ≥75 years of age are considered at high risk for CV disease, as stated in our article. Therefore, “Recommendation 3” for a target of <140 mm Hg is applicable for the population addressed in our article.1
- The Eighth Joint National Committee (JNC 8) does recommend a BP target <150 mm Hg for adults ≥60 years of age, but does not take into account recent data, which is why we wanted to highlight that data for physicians.2
- Since submission of our article, The American College of Cardiology/American Heart Association (ACC/AHA) has published its first set of guidelines since 2003, which lowered BP target to <130 mm Hg in patients with high CV risk. Those guidelines outline the validity of SPRINT and the consistency of the existing evidence, including the linear relationship of BP and mortality.3
- SPRINT was halted early specifically because of the mortality benefit in the intensive treatment group, which is ethically appropriate.4 It is unclear to us how this compromises the validity of the trial. There is often concern for bias from early cessation in small trials, but this was a large, well-powered trial.
- The ACC/AHA guidelines also address some of the nuances of ACCORD, which is specific to patients with diabetes (whom we excluded from our first Practice Recommendation). Although no overall mortality benefit was found, there was stroke reduction in this group and additional benefit in the standard glycemia group.3,5 A meta-analysis of SPRINT and ACCORD showed CV disease reduction with a BP target <120 mm Hg.6
Although we do believe that SPRINT is a landmark trial contributing a great deal to our recommendations, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions. We stressed that prescribers use caution and slow titration because of adverse effects. Geriatric medicine is a complex art, and one of the goals of our article was to highlight this complexity and emphasize the importance of considering goals of care, comorbidity, frailty, and cognitive function when choosing optimal BP targets.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
2. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
3. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
4. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
5. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
6. Perkovic V, Rodgers A. Redefining blood-pressure targets—SPRINT starts the marathon. N Engl Med. 2015;373:2175-2178.
In the article, “Hypertension treatment strategies for older adults” (J Fam Pract. 2017;66:546-554), Hansell et al recommend a systolic blood pressure (SBP) treatment target of <120 mm Hg for community-dwelling, nondiabetic patients ≥75 years of age. This recommendation is not supported by the authors’ cited guidelines, and we have serious concerns about the risk of harm from such overly stringent BP control in this population.
While Hansell et al acknowledge that no consensus exists regarding an optimal BP target for older patients, the authors cite the Eighth Joint National Committee (JNC 8), the American College of Physicians (ACP), the Systolic Blood Pressure Intervention Trial (SPRINT) subgroup analysis, and the BP arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to justify their recommendation. But as the authors mention, JNC 8 conducted a comprehensive review of the available evidence and determined that a BP target of <150/90 mm Hg for hypertensive patients ≥60 years of age is appropriate.1
The authors also state that ACP recommends an SBP target of <140 mm Hg, while, in fact, the recommendations from ACP (which are joint guidelines published with the American Academy of Family Physicians) say that high-quality evidence strongly supports an SBP target of <150 mm Hg to reduce the risk for mortality, stroke, and cardiac events in adults ≥60 years of age.2
SPRINT does support Hansell et al’s recommended SBP target of <120 mm Hg, but this trial provided only composite data of adults ≥75 years of age and did not differentiate between the outcomes in otherwise healthy adults ≥75 years of age vs those with cardiovascular conditions.3 As Hansell et al point out, the SPRINT trial was halted prematurely, which compromises the validity of their findings.
Lastly, the ACCORD trial did not find benefit to treating SBP <120 mm Hg compared with <140 mm Hg in adults with diabetes, but it did find substantial harms in the <120 mm Hg group, including an increased risk of renal impairment and hypokalemia.4
Hansel et al’s overreliance on the SPRINT subgroup analysis represents a significant flaw in the assertion that an SBP target <120 mm Hg is reasonable for all community-dwelling, non-diabetic adults ≥75 years of age. While the authors made the allowance that a higher target (<140 mm Hg) is acceptable if a target of <120 mm Hg places undue burden on the patient, the guidelines they cited, when considered together, suggest that starting at a higher target is not only sufficient to prevent complications, but also reduces overtreatment.
Adults ≥75 years of age are a diverse group regarding disease conditions, life expectancy, and personal priorities. While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines so that we can tailor BP treatment targets to each patient’s unique clinical situation and personal priorities. Applying a blanket recommendation to this heterogeneous population may result in significant harms from overtreatment.
Jennifer L. Middleton, MD, MPH, FAAFP; Miriam Chan, PharmD, CDE
Columbus, Ohio
1. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
2. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
3. Williamson JD, Suplano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA. 2016;315:2673-2682.
4. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585.
Authors’ response:
We agree with the title of this letter, “Utilize guidelines, but customize BP treatment in older patients.” Our recommendations are not limited to targeting a systolic BP <120 mm Hg for community-dwelling, nondiabetic adults ≥75 years of age, but include consideration for “undue burden.” Our third practice recommendation, which recommends that one consider cognitive function, polypharmacy, multimorbidity, and frailty, is an equally—if not more—important recommendation.
With regard to the specific concerns about the current guidelines:
- The American College of Physicians and American Academy of Family Physicians’ “Recommendation 1” advocates a systolic BP goal <150 mm Hg for adults ≥60 years of age. However, “Recommendation 3” endorses intensifying treatment in adults ≥60 years of age at high cardiovascular (CV) risk. Based on Framingham criteria, all adults ≥75 years of age are considered at high risk for CV disease, as stated in our article. Therefore, “Recommendation 3” for a target of <140 mm Hg is applicable for the population addressed in our article.1
- The Eighth Joint National Committee (JNC 8) does recommend a BP target <150 mm Hg for adults ≥60 years of age, but does not take into account recent data, which is why we wanted to highlight that data for physicians.2
- Since submission of our article, The American College of Cardiology/American Heart Association (ACC/AHA) has published its first set of guidelines since 2003, which lowered BP target to <130 mm Hg in patients with high CV risk. Those guidelines outline the validity of SPRINT and the consistency of the existing evidence, including the linear relationship of BP and mortality.3
- SPRINT was halted early specifically because of the mortality benefit in the intensive treatment group, which is ethically appropriate.4 It is unclear to us how this compromises the validity of the trial. There is often concern for bias from early cessation in small trials, but this was a large, well-powered trial.
- The ACC/AHA guidelines also address some of the nuances of ACCORD, which is specific to patients with diabetes (whom we excluded from our first Practice Recommendation). Although no overall mortality benefit was found, there was stroke reduction in this group and additional benefit in the standard glycemia group.3,5 A meta-analysis of SPRINT and ACCORD showed CV disease reduction with a BP target <120 mm Hg.6
Although we do believe that SPRINT is a landmark trial contributing a great deal to our recommendations, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions. We stressed that prescribers use caution and slow titration because of adverse effects. Geriatric medicine is a complex art, and one of the goals of our article was to highlight this complexity and emphasize the importance of considering goals of care, comorbidity, frailty, and cognitive function when choosing optimal BP targets.
Maggie W. Hansell, MD; Emily M. Mann, MD; Julienne K. Kirk, PharmD
Winston-Salem, NC
1. Qaseem A, Wilt TJ, Rich R, et al. Pharmacological treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2017;166:430-437.
2. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
3. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Available at: http://hyper.ahajournals.org/content/hypertensionaha/early/2017/11/10/HYP.0000000000000066.full.pdf. Accessed December 12, 2017.
4. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2106.
5. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive blood-pressure control in type 2 diabetes. N Engl J Med. 2010;362:1575-1585.
6. Perkovic V, Rodgers A. Redefining blood-pressure targets—SPRINT starts the marathon. N Engl Med. 2015;373:2175-2178.
Weakness with left elbow flexion • left anterior shoulder pain • Dx?
THE CASE
A 41-year-old, right-hand dominant man sought care at our facility one day after trying to pull his boat out of the water. He’d tried to lift the boat with his hands while his forearms were fully supinated and his elbows were flexed to about 90°. He then felt a sharp burning sensation in his left anterior shoulder and was unable to lift the boat. The patient denied feeling a popping sensation at the time of the injury. He had mild pain at night, but was able to sleep. He said that he had mild diminished strength with elbow flexion, but denied having any numbness, tingling, or discoloration of his skin.
The patient said he did weightlifting and strength training of his upper and lower extremities 4 times/week. He was in good general health, was not taking any medications or supplements, and denied smoking or using illicit drugs. His surgical history was significant for a Bankart repair 8 years ago.
On physical examination, the patient had a scar from the previous surgery, a hollow area in his left anterior shoulder, and a prominent biceps muscle belly (FIGURE). His shoulder range of motion was normal. Left shoulder Neer, Hawkins-Kennedy, drop-arm, cross-arm, empty can, and apprehension tests were negative. A left Speed’s test (resisted elbow flexion when elbow is flexed 20° to 30° with the forearm in supination and the arm in about 60° of flexion) was positive for mild anterior shoulder pain. So, too, was a Yergason’s test (resisted forearm supination and elbow flexion when forearm is pronated and elbow is flexed to 90°). The patient’s elbow flexion strength was 4 out of 5, and his supination strength was 5 out of 5. Neurovascular and sensory examinations of his upper extremities, including radial and ulnar pulses, were normal.
THE DIAGNOSIS
A diagnostic musculoskeletal ultrasound revealed an empty tendon sheath of the long head of the biceps in the bicipital groove and a retracted echogenic stump with associated hematoma at the proximal musculotendinous junction. Based on the patient’s history, physical examination, and ultrasound, a diagnosis of an acute rupture of the left long head of the biceps brachii tendon was made.
DISCUSSION
Diagnosis of acute rupture is often made clinically based on a visually apparent defect proximally and a bulbous mass distally (“Popeye deformity”).1 Ultrasound and magnetic resonance imaging (MRI) may aid in the diagnosis by demonstrating an absence of the long head in the bicipital groove or at its insertion.
The biceps brachii tendon functions in flexion and supination of the forearm. The long head of the biceps also plays a stabilizing role in the glenohumeral joint during elbow flexion and supination.2 Injury to the biceps most often occurs in middle-aged men following a traumatic sudden eccentric bicipital contraction event, during which most patients describe a snapping or popping sensation.3,4
Rupture of the proximal biceps tendon represents about 90% of all biceps ruptures, which almost exclusively involve the long head of the biceps.3,5,6 Risk factors for tendon rupture include obesity, smoking, steroid injection in or around the tendon, and previous tendinopathy.7-10
Functional limitations. It is generally thought that functional limitations following a proximal biceps rupture are relatively minimal, due to the work of other flexors and supinators, including the brachialis and brachioradialis. However, because strength and endurance of the muscle can decrease by about 25%, physical laborers and high-demand athletes may notice a degree of residual weakness with supination and elbow flexion.11,12
Surgery is suitable for some, but not all
Surgical repair is recommended for acute ruptures in patients with high physical demands and for whom a slight loss of flexion and supination strength would not be well tolerated.13 Tenotomy and tenodesis are the main techniques used to surgically repair a rupture of the long head of the biceps brachii tendon. Although there is no consensus on which technique is superior, it seems that there is less cosmetic deformity and better post-surgery biomechanical strength with tenodesis compared with tenotomy.14 However, tenodesis is associated with a higher likelihood of bicipital pain,14 and recent case reports have suggested it is associated with an increased risk of humeral fracture.15 Therefore, each patient should be treated on an individual case basis, taking into account age, activity level, and physical demand.14
For most patients, treatment remains conservative with typically excellent outcomes. Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder. Such exercises can be started almost immediately after injury. In one study, nonoperative management was recommended for patients with sedentary work, injury in the non-dominant arm, and acceptable cosmetic deformity. Researchers noted that patients who opt for a nonsurgical treatment generally do well with a home exercise program and rarely have stiffness.1
If the patient is a young athlete, if cosmetic deformity is unacceptable, or if the injury is in the dominant arm of a laborer, then the patient may want to consider tenodesis.1 Tangari et al found that in high-demand athletes, biceps tenodesis resulted in excellent functional and cosmetic results with no clinically significant decrease in strength after an average follow-up of 7.6 years.13 In a case s
Our patient elected to proceed with a tenodesis procedure. Two months after the surgery, he had fully recovered.
THE TAKEAWAY
Rupture of the biceps brachii tendon is relatively uncommon. In the vast majority of cases, it happens in the long head of the dominant arm of middle-aged men. Diagnosis is mainly clinical; however, ultrasound and MRI can confirm the diagnosis when there is doubt. Nonoperative management is appropriate for the majority of patients. Young athletes, patients who are concerned with cosmetic appearance, and labor workers with injury to their dominant arm should be referred to an orthopedic surgeon for possible surgery.
1. Geaney LE, Mazzocca AD. Biceps brachii tendon ruptures: a review of diagnosis and treatment of proximal and distal biceps tendon ruptures. Phys Sportsmed. 2010;38:117-125.
2. Payne LZ, Deng XH, Craig EV, et al. The combined dynamic and static contributions to subacromial impingement. A biomechanical analysis. Am J Sports Med. 1997;25:801-808.
3. Jayamoorthy T, Field JR, Costi JJ, et al. Biceps tenodesis: a biomechanical study of fixation methods. J Shoulder Elbow Surg. 2004;13:160-164.
4. Mazzocca AD, Spang JT, Arciero RA. Distal biceps rupture. Orthop Clin North Am. 2008;39:237-249, vii.
5. Carter AN, Erickson SM. Proximal biceps tendon rupture: primarily an injury of middle age. Phys Sportsmed. 1999;27:95-101.
6. Elser F, Braun S, Dewing CB, et al. Anatomy, function, injuries, and treatment of the long head of the biceps brachii tendon. Arthroscopy. 2011;27:581-592.
7. Kelly MP, Perkinson SG, Ablove RH, et al. Distal biceps tendon ruptures: an epidemiological analysis using a large population database. Am J Sports Med. 2015;43:2012-2017.
8. Schneider A, Bennett JM, O’Connor DP, et al. Bilateral ruptures of the distal biceps brachii tendon. J Shoulder Elbow Surg. 2009;18:804-807.
9. Sethi N, Wright R, Yamaguchi K. Disorders of the long head of the biceps tendon. J Shoulder Elbow Surg. 1999;8:644-654.
10. The Physician and Sportsmedicine. Complete rupture of large tendons. Risk factors, signs, and definitive treatment. Available at: https://orthony.com/directory/uploads/flik_complete-rupture-of-large-tendons.pdf. Accessed December 8, 2017.
11. Pearl ML, Bessos K, Wong K. Strength deficits related to distal biceps tendon rupture and repair. A case report. Am J Sports Med. 1998;26:295-296.
12. Deutch SR, Gelineck J, Johannsen HV, et al. Permanent disabilities in the displaced muscle from rupture of the long head tendon of the biceps. Scand J Med Sci Sports. 2005;15:159-162.
13. Tangari M, Carbone S, Gallo M, et al. Long head of the biceps tendon rupture in professional wrestlers: treatment with a mini-open tenodesis. J Shoulder Elbow Surg. 2011;20:409-413.
14. Hsu AR, Ghodadra NS, Provencher MT, et al. Biceps tenotomy versus tenodesis: a review of clinical outcomes and biomechanical results. J Shoulder Elbow Surg. 2011;20:326-332.
15. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20:e7-e11.
THE CASE
A 41-year-old, right-hand dominant man sought care at our facility one day after trying to pull his boat out of the water. He’d tried to lift the boat with his hands while his forearms were fully supinated and his elbows were flexed to about 90°. He then felt a sharp burning sensation in his left anterior shoulder and was unable to lift the boat. The patient denied feeling a popping sensation at the time of the injury. He had mild pain at night, but was able to sleep. He said that he had mild diminished strength with elbow flexion, but denied having any numbness, tingling, or discoloration of his skin.
The patient said he did weightlifting and strength training of his upper and lower extremities 4 times/week. He was in good general health, was not taking any medications or supplements, and denied smoking or using illicit drugs. His surgical history was significant for a Bankart repair 8 years ago.
On physical examination, the patient had a scar from the previous surgery, a hollow area in his left anterior shoulder, and a prominent biceps muscle belly (FIGURE). His shoulder range of motion was normal. Left shoulder Neer, Hawkins-Kennedy, drop-arm, cross-arm, empty can, and apprehension tests were negative. A left Speed’s test (resisted elbow flexion when elbow is flexed 20° to 30° with the forearm in supination and the arm in about 60° of flexion) was positive for mild anterior shoulder pain. So, too, was a Yergason’s test (resisted forearm supination and elbow flexion when forearm is pronated and elbow is flexed to 90°). The patient’s elbow flexion strength was 4 out of 5, and his supination strength was 5 out of 5. Neurovascular and sensory examinations of his upper extremities, including radial and ulnar pulses, were normal.
THE DIAGNOSIS
A diagnostic musculoskeletal ultrasound revealed an empty tendon sheath of the long head of the biceps in the bicipital groove and a retracted echogenic stump with associated hematoma at the proximal musculotendinous junction. Based on the patient’s history, physical examination, and ultrasound, a diagnosis of an acute rupture of the left long head of the biceps brachii tendon was made.
DISCUSSION
Diagnosis of acute rupture is often made clinically based on a visually apparent defect proximally and a bulbous mass distally (“Popeye deformity”).1 Ultrasound and magnetic resonance imaging (MRI) may aid in the diagnosis by demonstrating an absence of the long head in the bicipital groove or at its insertion.
The biceps brachii tendon functions in flexion and supination of the forearm. The long head of the biceps also plays a stabilizing role in the glenohumeral joint during elbow flexion and supination.2 Injury to the biceps most often occurs in middle-aged men following a traumatic sudden eccentric bicipital contraction event, during which most patients describe a snapping or popping sensation.3,4
Rupture of the proximal biceps tendon represents about 90% of all biceps ruptures, which almost exclusively involve the long head of the biceps.3,5,6 Risk factors for tendon rupture include obesity, smoking, steroid injection in or around the tendon, and previous tendinopathy.7-10
Functional limitations. It is generally thought that functional limitations following a proximal biceps rupture are relatively minimal, due to the work of other flexors and supinators, including the brachialis and brachioradialis. However, because strength and endurance of the muscle can decrease by about 25%, physical laborers and high-demand athletes may notice a degree of residual weakness with supination and elbow flexion.11,12
Surgery is suitable for some, but not all
Surgical repair is recommended for acute ruptures in patients with high physical demands and for whom a slight loss of flexion and supination strength would not be well tolerated.13 Tenotomy and tenodesis are the main techniques used to surgically repair a rupture of the long head of the biceps brachii tendon. Although there is no consensus on which technique is superior, it seems that there is less cosmetic deformity and better post-surgery biomechanical strength with tenodesis compared with tenotomy.14 However, tenodesis is associated with a higher likelihood of bicipital pain,14 and recent case reports have suggested it is associated with an increased risk of humeral fracture.15 Therefore, each patient should be treated on an individual case basis, taking into account age, activity level, and physical demand.14
For most patients, treatment remains conservative with typically excellent outcomes. Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder. Such exercises can be started almost immediately after injury. In one study, nonoperative management was recommended for patients with sedentary work, injury in the non-dominant arm, and acceptable cosmetic deformity. Researchers noted that patients who opt for a nonsurgical treatment generally do well with a home exercise program and rarely have stiffness.1
If the patient is a young athlete, if cosmetic deformity is unacceptable, or if the injury is in the dominant arm of a laborer, then the patient may want to consider tenodesis.1 Tangari et al found that in high-demand athletes, biceps tenodesis resulted in excellent functional and cosmetic results with no clinically significant decrease in strength after an average follow-up of 7.6 years.13 In a case s
Our patient elected to proceed with a tenodesis procedure. Two months after the surgery, he had fully recovered.
THE TAKEAWAY
Rupture of the biceps brachii tendon is relatively uncommon. In the vast majority of cases, it happens in the long head of the dominant arm of middle-aged men. Diagnosis is mainly clinical; however, ultrasound and MRI can confirm the diagnosis when there is doubt. Nonoperative management is appropriate for the majority of patients. Young athletes, patients who are concerned with cosmetic appearance, and labor workers with injury to their dominant arm should be referred to an orthopedic surgeon for possible surgery.
THE CASE
A 41-year-old, right-hand dominant man sought care at our facility one day after trying to pull his boat out of the water. He’d tried to lift the boat with his hands while his forearms were fully supinated and his elbows were flexed to about 90°. He then felt a sharp burning sensation in his left anterior shoulder and was unable to lift the boat. The patient denied feeling a popping sensation at the time of the injury. He had mild pain at night, but was able to sleep. He said that he had mild diminished strength with elbow flexion, but denied having any numbness, tingling, or discoloration of his skin.
The patient said he did weightlifting and strength training of his upper and lower extremities 4 times/week. He was in good general health, was not taking any medications or supplements, and denied smoking or using illicit drugs. His surgical history was significant for a Bankart repair 8 years ago.
On physical examination, the patient had a scar from the previous surgery, a hollow area in his left anterior shoulder, and a prominent biceps muscle belly (FIGURE). His shoulder range of motion was normal. Left shoulder Neer, Hawkins-Kennedy, drop-arm, cross-arm, empty can, and apprehension tests were negative. A left Speed’s test (resisted elbow flexion when elbow is flexed 20° to 30° with the forearm in supination and the arm in about 60° of flexion) was positive for mild anterior shoulder pain. So, too, was a Yergason’s test (resisted forearm supination and elbow flexion when forearm is pronated and elbow is flexed to 90°). The patient’s elbow flexion strength was 4 out of 5, and his supination strength was 5 out of 5. Neurovascular and sensory examinations of his upper extremities, including radial and ulnar pulses, were normal.
THE DIAGNOSIS
A diagnostic musculoskeletal ultrasound revealed an empty tendon sheath of the long head of the biceps in the bicipital groove and a retracted echogenic stump with associated hematoma at the proximal musculotendinous junction. Based on the patient’s history, physical examination, and ultrasound, a diagnosis of an acute rupture of the left long head of the biceps brachii tendon was made.
DISCUSSION
Diagnosis of acute rupture is often made clinically based on a visually apparent defect proximally and a bulbous mass distally (“Popeye deformity”).1 Ultrasound and magnetic resonance imaging (MRI) may aid in the diagnosis by demonstrating an absence of the long head in the bicipital groove or at its insertion.
The biceps brachii tendon functions in flexion and supination of the forearm. The long head of the biceps also plays a stabilizing role in the glenohumeral joint during elbow flexion and supination.2 Injury to the biceps most often occurs in middle-aged men following a traumatic sudden eccentric bicipital contraction event, during which most patients describe a snapping or popping sensation.3,4
Rupture of the proximal biceps tendon represents about 90% of all biceps ruptures, which almost exclusively involve the long head of the biceps.3,5,6 Risk factors for tendon rupture include obesity, smoking, steroid injection in or around the tendon, and previous tendinopathy.7-10
Functional limitations. It is generally thought that functional limitations following a proximal biceps rupture are relatively minimal, due to the work of other flexors and supinators, including the brachialis and brachioradialis. However, because strength and endurance of the muscle can decrease by about 25%, physical laborers and high-demand athletes may notice a degree of residual weakness with supination and elbow flexion.11,12
Surgery is suitable for some, but not all
Surgical repair is recommended for acute ruptures in patients with high physical demands and for whom a slight loss of flexion and supination strength would not be well tolerated.13 Tenotomy and tenodesis are the main techniques used to surgically repair a rupture of the long head of the biceps brachii tendon. Although there is no consensus on which technique is superior, it seems that there is less cosmetic deformity and better post-surgery biomechanical strength with tenodesis compared with tenotomy.14 However, tenodesis is associated with a higher likelihood of bicipital pain,14 and recent case reports have suggested it is associated with an increased risk of humeral fracture.15 Therefore, each patient should be treated on an individual case basis, taking into account age, activity level, and physical demand.14
For most patients, treatment remains conservative with typically excellent outcomes. Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder. Such exercises can be started almost immediately after injury. In one study, nonoperative management was recommended for patients with sedentary work, injury in the non-dominant arm, and acceptable cosmetic deformity. Researchers noted that patients who opt for a nonsurgical treatment generally do well with a home exercise program and rarely have stiffness.1
If the patient is a young athlete, if cosmetic deformity is unacceptable, or if the injury is in the dominant arm of a laborer, then the patient may want to consider tenodesis.1 Tangari et al found that in high-demand athletes, biceps tenodesis resulted in excellent functional and cosmetic results with no clinically significant decrease in strength after an average follow-up of 7.6 years.13 In a case s
Our patient elected to proceed with a tenodesis procedure. Two months after the surgery, he had fully recovered.
THE TAKEAWAY
Rupture of the biceps brachii tendon is relatively uncommon. In the vast majority of cases, it happens in the long head of the dominant arm of middle-aged men. Diagnosis is mainly clinical; however, ultrasound and MRI can confirm the diagnosis when there is doubt. Nonoperative management is appropriate for the majority of patients. Young athletes, patients who are concerned with cosmetic appearance, and labor workers with injury to their dominant arm should be referred to an orthopedic surgeon for possible surgery.
1. Geaney LE, Mazzocca AD. Biceps brachii tendon ruptures: a review of diagnosis and treatment of proximal and distal biceps tendon ruptures. Phys Sportsmed. 2010;38:117-125.
2. Payne LZ, Deng XH, Craig EV, et al. The combined dynamic and static contributions to subacromial impingement. A biomechanical analysis. Am J Sports Med. 1997;25:801-808.
3. Jayamoorthy T, Field JR, Costi JJ, et al. Biceps tenodesis: a biomechanical study of fixation methods. J Shoulder Elbow Surg. 2004;13:160-164.
4. Mazzocca AD, Spang JT, Arciero RA. Distal biceps rupture. Orthop Clin North Am. 2008;39:237-249, vii.
5. Carter AN, Erickson SM. Proximal biceps tendon rupture: primarily an injury of middle age. Phys Sportsmed. 1999;27:95-101.
6. Elser F, Braun S, Dewing CB, et al. Anatomy, function, injuries, and treatment of the long head of the biceps brachii tendon. Arthroscopy. 2011;27:581-592.
7. Kelly MP, Perkinson SG, Ablove RH, et al. Distal biceps tendon ruptures: an epidemiological analysis using a large population database. Am J Sports Med. 2015;43:2012-2017.
8. Schneider A, Bennett JM, O’Connor DP, et al. Bilateral ruptures of the distal biceps brachii tendon. J Shoulder Elbow Surg. 2009;18:804-807.
9. Sethi N, Wright R, Yamaguchi K. Disorders of the long head of the biceps tendon. J Shoulder Elbow Surg. 1999;8:644-654.
10. The Physician and Sportsmedicine. Complete rupture of large tendons. Risk factors, signs, and definitive treatment. Available at: https://orthony.com/directory/uploads/flik_complete-rupture-of-large-tendons.pdf. Accessed December 8, 2017.
11. Pearl ML, Bessos K, Wong K. Strength deficits related to distal biceps tendon rupture and repair. A case report. Am J Sports Med. 1998;26:295-296.
12. Deutch SR, Gelineck J, Johannsen HV, et al. Permanent disabilities in the displaced muscle from rupture of the long head tendon of the biceps. Scand J Med Sci Sports. 2005;15:159-162.
13. Tangari M, Carbone S, Gallo M, et al. Long head of the biceps tendon rupture in professional wrestlers: treatment with a mini-open tenodesis. J Shoulder Elbow Surg. 2011;20:409-413.
14. Hsu AR, Ghodadra NS, Provencher MT, et al. Biceps tenotomy versus tenodesis: a review of clinical outcomes and biomechanical results. J Shoulder Elbow Surg. 2011;20:326-332.
15. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20:e7-e11.
1. Geaney LE, Mazzocca AD. Biceps brachii tendon ruptures: a review of diagnosis and treatment of proximal and distal biceps tendon ruptures. Phys Sportsmed. 2010;38:117-125.
2. Payne LZ, Deng XH, Craig EV, et al. The combined dynamic and static contributions to subacromial impingement. A biomechanical analysis. Am J Sports Med. 1997;25:801-808.
3. Jayamoorthy T, Field JR, Costi JJ, et al. Biceps tenodesis: a biomechanical study of fixation methods. J Shoulder Elbow Surg. 2004;13:160-164.
4. Mazzocca AD, Spang JT, Arciero RA. Distal biceps rupture. Orthop Clin North Am. 2008;39:237-249, vii.
5. Carter AN, Erickson SM. Proximal biceps tendon rupture: primarily an injury of middle age. Phys Sportsmed. 1999;27:95-101.
6. Elser F, Braun S, Dewing CB, et al. Anatomy, function, injuries, and treatment of the long head of the biceps brachii tendon. Arthroscopy. 2011;27:581-592.
7. Kelly MP, Perkinson SG, Ablove RH, et al. Distal biceps tendon ruptures: an epidemiological analysis using a large population database. Am J Sports Med. 2015;43:2012-2017.
8. Schneider A, Bennett JM, O’Connor DP, et al. Bilateral ruptures of the distal biceps brachii tendon. J Shoulder Elbow Surg. 2009;18:804-807.
9. Sethi N, Wright R, Yamaguchi K. Disorders of the long head of the biceps tendon. J Shoulder Elbow Surg. 1999;8:644-654.
10. The Physician and Sportsmedicine. Complete rupture of large tendons. Risk factors, signs, and definitive treatment. Available at: https://orthony.com/directory/uploads/flik_complete-rupture-of-large-tendons.pdf. Accessed December 8, 2017.
11. Pearl ML, Bessos K, Wong K. Strength deficits related to distal biceps tendon rupture and repair. A case report. Am J Sports Med. 1998;26:295-296.
12. Deutch SR, Gelineck J, Johannsen HV, et al. Permanent disabilities in the displaced muscle from rupture of the long head tendon of the biceps. Scand J Med Sci Sports. 2005;15:159-162.
13. Tangari M, Carbone S, Gallo M, et al. Long head of the biceps tendon rupture in professional wrestlers: treatment with a mini-open tenodesis. J Shoulder Elbow Surg. 2011;20:409-413.
14. Hsu AR, Ghodadra NS, Provencher MT, et al. Biceps tenotomy versus tenodesis: a review of clinical outcomes and biomechanical results. J Shoulder Elbow Surg. 2011;20:326-332.
15. Sears BW, Spencer EE, Getz CL. Humeral fracture following subpectoral biceps tenodesis in 2 active, healthy patients. J Shoulder Elbow Surg. 2011;20:e7-e11.
Painful jaw lesion
A 48-year-old Chinese woman was referred to our center with a 7-month history of a painful lesion on her left jaw that had been gradually increasing in size. The patient noted occasional purulent and bloody discharge from the lesion. She denied having a toothache.
An examination revealed an erythematous nodule with perilesional puckering superior to the left body of the mandible, measuring 7 × 8 mm, with no discharge or surrounding inflammation (FIGURE 1). There was no cervical lymphadenopathy.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Odontogenic sinus tract
Further examination on the inside of the patient’s mouth revealed root stumps of the left inferior molars (FIGURE 2). Based on the appearance of the lesion and molar involvement, we diagnosed odontogenic sinus tract (OST). OST, also known as odontogenic fistula or dental sinus, is a clinical diagnosis.
Symptoms such as odontalgia may be present in only 50% of patients with OST; thus, patients often initially consult their physician, rather than their dentist.1 If OST is suspected, evaluation should begin with a thorough history focusing on any recent facial trauma or past dental diseases. Dental panoramic or periapical radiography can be performed to confirm the extent of dental disease, and pulp vitality testing can determine if a diseased tooth is restorable.
A biopsy of the sinus tract is not required, as it would only reveal granulation tissue. Bimanual palpation of the oral cavity may reveal a cord-like structure from the cutaneous sinus to the underlying alveolar bone. (This structure was palpated in our patient.)
The pathogenesis of OST begins with dental caries, which progress to degeneration of the pulp and formation of periapical abscesses and root stumps. Progressive suppuration causes local destruction and subsequent tract formation through the alveolar bone and mandible. The build-up in pressure within this tract results in an eruption through the skin, manifesting as a sinus with extrusion of pus. The most common site of OST is at the angle of the mandible.2
The differential Dx is limited
There are a small number of other cutaneous conditions that may arise in the region of the mandible, but they have clinical features that distinguish them from OST.
Pyogenic granuloma presents as an erythematous papule that bleeds on contact. It usually develops rapidly following antecedent trauma.
Actinomycosis usually appears as an indolent plaque, with draining sinuses that extrude yellow grains on pressure. It may result from an underlying dental infection.
Squamous cell carcinoma of the skin often presents as a scaly plaque or non-healing ulcer with irregular margins and everted edges.
A furuncle is a tender, erythematous papule or nodule centered on a hair follicle. It is commonly associated with Staphylococcus aureus infection.
Treating OST
Treatment requires endodontic referral for root canal therapy, after which most cases resolve within a few weeks. OST can heal with post-inflammatory hyper- or hypopigmentation as a result of melanocyte damage. Systemic antibiotic administration is not necessary.3
We referred our patient to a dentist, who removed the root stumps and provided root canal treatment. The OST healed within several weeks. The patient had residual hypopigmentation after the OST healed, but was satisfied with the outcome.
CORRESPONDENCE
Hua-Liang Joel Lim, MBBS, MMed, National Skin Centre, 1 Mandalay Rd, Singapore 308205; [email protected].
1. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol. 1986;14:94-100.
2. Brown RS, Jones R, Feimster T, et al. Cutaneous sinus tracts (or emerging sinus tracts) of odontogenic origin: a report of 3 cases. Clin Cosmet Investig Dent. 2010;2:63-67.
3. Susic M, Krakar N, Borcic J, et al. Odontogenic sinus tract to the neck skin: a case report. J Dermatol. 2004;31:920-922.
A 48-year-old Chinese woman was referred to our center with a 7-month history of a painful lesion on her left jaw that had been gradually increasing in size. The patient noted occasional purulent and bloody discharge from the lesion. She denied having a toothache.
An examination revealed an erythematous nodule with perilesional puckering superior to the left body of the mandible, measuring 7 × 8 mm, with no discharge or surrounding inflammation (FIGURE 1). There was no cervical lymphadenopathy.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Odontogenic sinus tract
Further examination on the inside of the patient’s mouth revealed root stumps of the left inferior molars (FIGURE 2). Based on the appearance of the lesion and molar involvement, we diagnosed odontogenic sinus tract (OST). OST, also known as odontogenic fistula or dental sinus, is a clinical diagnosis.
Symptoms such as odontalgia may be present in only 50% of patients with OST; thus, patients often initially consult their physician, rather than their dentist.1 If OST is suspected, evaluation should begin with a thorough history focusing on any recent facial trauma or past dental diseases. Dental panoramic or periapical radiography can be performed to confirm the extent of dental disease, and pulp vitality testing can determine if a diseased tooth is restorable.
A biopsy of the sinus tract is not required, as it would only reveal granulation tissue. Bimanual palpation of the oral cavity may reveal a cord-like structure from the cutaneous sinus to the underlying alveolar bone. (This structure was palpated in our patient.)
The pathogenesis of OST begins with dental caries, which progress to degeneration of the pulp and formation of periapical abscesses and root stumps. Progressive suppuration causes local destruction and subsequent tract formation through the alveolar bone and mandible. The build-up in pressure within this tract results in an eruption through the skin, manifesting as a sinus with extrusion of pus. The most common site of OST is at the angle of the mandible.2
The differential Dx is limited
There are a small number of other cutaneous conditions that may arise in the region of the mandible, but they have clinical features that distinguish them from OST.
Pyogenic granuloma presents as an erythematous papule that bleeds on contact. It usually develops rapidly following antecedent trauma.
Actinomycosis usually appears as an indolent plaque, with draining sinuses that extrude yellow grains on pressure. It may result from an underlying dental infection.
Squamous cell carcinoma of the skin often presents as a scaly plaque or non-healing ulcer with irregular margins and everted edges.
A furuncle is a tender, erythematous papule or nodule centered on a hair follicle. It is commonly associated with Staphylococcus aureus infection.
Treating OST
Treatment requires endodontic referral for root canal therapy, after which most cases resolve within a few weeks. OST can heal with post-inflammatory hyper- or hypopigmentation as a result of melanocyte damage. Systemic antibiotic administration is not necessary.3
We referred our patient to a dentist, who removed the root stumps and provided root canal treatment. The OST healed within several weeks. The patient had residual hypopigmentation after the OST healed, but was satisfied with the outcome.
CORRESPONDENCE
Hua-Liang Joel Lim, MBBS, MMed, National Skin Centre, 1 Mandalay Rd, Singapore 308205; [email protected].
A 48-year-old Chinese woman was referred to our center with a 7-month history of a painful lesion on her left jaw that had been gradually increasing in size. The patient noted occasional purulent and bloody discharge from the lesion. She denied having a toothache.
An examination revealed an erythematous nodule with perilesional puckering superior to the left body of the mandible, measuring 7 × 8 mm, with no discharge or surrounding inflammation (FIGURE 1). There was no cervical lymphadenopathy.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Odontogenic sinus tract
Further examination on the inside of the patient’s mouth revealed root stumps of the left inferior molars (FIGURE 2). Based on the appearance of the lesion and molar involvement, we diagnosed odontogenic sinus tract (OST). OST, also known as odontogenic fistula or dental sinus, is a clinical diagnosis.
Symptoms such as odontalgia may be present in only 50% of patients with OST; thus, patients often initially consult their physician, rather than their dentist.1 If OST is suspected, evaluation should begin with a thorough history focusing on any recent facial trauma or past dental diseases. Dental panoramic or periapical radiography can be performed to confirm the extent of dental disease, and pulp vitality testing can determine if a diseased tooth is restorable.
A biopsy of the sinus tract is not required, as it would only reveal granulation tissue. Bimanual palpation of the oral cavity may reveal a cord-like structure from the cutaneous sinus to the underlying alveolar bone. (This structure was palpated in our patient.)
The pathogenesis of OST begins with dental caries, which progress to degeneration of the pulp and formation of periapical abscesses and root stumps. Progressive suppuration causes local destruction and subsequent tract formation through the alveolar bone and mandible. The build-up in pressure within this tract results in an eruption through the skin, manifesting as a sinus with extrusion of pus. The most common site of OST is at the angle of the mandible.2
The differential Dx is limited
There are a small number of other cutaneous conditions that may arise in the region of the mandible, but they have clinical features that distinguish them from OST.
Pyogenic granuloma presents as an erythematous papule that bleeds on contact. It usually develops rapidly following antecedent trauma.
Actinomycosis usually appears as an indolent plaque, with draining sinuses that extrude yellow grains on pressure. It may result from an underlying dental infection.
Squamous cell carcinoma of the skin often presents as a scaly plaque or non-healing ulcer with irregular margins and everted edges.
A furuncle is a tender, erythematous papule or nodule centered on a hair follicle. It is commonly associated with Staphylococcus aureus infection.
Treating OST
Treatment requires endodontic referral for root canal therapy, after which most cases resolve within a few weeks. OST can heal with post-inflammatory hyper- or hypopigmentation as a result of melanocyte damage. Systemic antibiotic administration is not necessary.3
We referred our patient to a dentist, who removed the root stumps and provided root canal treatment. The OST healed within several weeks. The patient had residual hypopigmentation after the OST healed, but was satisfied with the outcome.
CORRESPONDENCE
Hua-Liang Joel Lim, MBBS, MMed, National Skin Centre, 1 Mandalay Rd, Singapore 308205; [email protected].
1. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol. 1986;14:94-100.
2. Brown RS, Jones R, Feimster T, et al. Cutaneous sinus tracts (or emerging sinus tracts) of odontogenic origin: a report of 3 cases. Clin Cosmet Investig Dent. 2010;2:63-67.
3. Susic M, Krakar N, Borcic J, et al. Odontogenic sinus tract to the neck skin: a case report. J Dermatol. 2004;31:920-922.
1. Cioffi GA, Terezhalmy GT, Parlette HL. Cutaneous draining sinus tract: an odontogenic etiology. J Am Acad Dermatol. 1986;14:94-100.
2. Brown RS, Jones R, Feimster T, et al. Cutaneous sinus tracts (or emerging sinus tracts) of odontogenic origin: a report of 3 cases. Clin Cosmet Investig Dent. 2010;2:63-67.
3. Susic M, Krakar N, Borcic J, et al. Odontogenic sinus tract to the neck skin: a case report. J Dermatol. 2004;31:920-922.
Worsening dyspnea
A 62-year-old woman presented with a 2- to 3-week history of fatigue, nonproductive cough, dyspnea on exertion, and intermittent fever/chills. Her past medical history was significant for rheumatoid arthritis (RA) that had been treated with methotrexate and prednisone for the past 6 years. The patient was currently smoking half a pack a day with a 40-pack year history. The patient was a lifelong resident of Arizona and had previously worked in a stone mine.
On physical examination she appeared comfortable without any increased work of breathing. Her vital signs included a temperature of 36.6° C, a blood pressure of 110/54 mm Hg, a pulse of 90 beats/min, respirations of 16/min, and room-air oxygen saturation of 87%. Pulmonary examination revealed scattered wheezes with fine bibasilar crackles. The remainder of her physical exam was normal. Because she was hypoxic, she was admitted to the hospital.
At the hospital, a chest x-ray showed diffuse, bilateral interstitial changes (FIGURE 1). Laboratory tests revealed a white blood cell count of 13,800/mcL (normal: 4500-10,500/mcL) with 73% neutrophils (normal: 40%-60%), 3% bands (normal: 0-3%), 14% monocytes (normal: 2%-8%), 6% eosinophils (normal: 1%-4%), and 3% lymphocytes (normal: 20%-30%). Community-acquired pneumonia was suspected, and the patient was started on levofloxacin. Over the next 2 days, her dyspnea worsened. She became tachycardic, and her oxygen requirement increased to 15 L/min via a non-rebreather mask. She was transferred to the intensive care unit.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Interstitial lung disease
Given the patient’s worsening respiratory status, a computed tomography (CT) scan was ordered (FIGURE 2). Review of the CT scan showed ground-glass opacification, mild subpleural honeycombing, reticularity, and traction bronchiectasis bilaterally at the lung bases. Bronchoscopy with lavage was performed to rule out infectious etiologies and was negative. These findings, along with the patient’s medical history of RA and use of methotrexate, led us to diagnose interstitial lung disease (ILD) in this patient.
ILD refers to a group of disorders that primarily affects the pulmonary interstitium, rather than the alveolar spaces or pleura.1 The most common causes of ILD seen in primary care are idiopathic pulmonary fibrosis, connective tissue disease, and hypersensitivity pneumonitis secondary to drugs (such as methotrexate, citalopram, fluoxetine, nitrofurantoin, and cephalosporins), radiation, or occupational exposures. (Textile, metal, and plastic workers are at a heightened risk, as are painters and individuals who work with animals.)1 In 2010, idiopathic pulmonary fibrosis had a prevalence of 18.2 cases per 100,000 people.2 Determining the underlying cause of ILD is important, as it may influence prognosis and treatment decisions.
The most common presenting symptoms of ILD are exertional dyspnea, cough with insidious onset, fatigue, and weakness.1,3 Bear in mind, however, that patients with ILD associated with a connective tissue disease may have more subtle manifestations of exertional dyspnea, such as a change in activity level or low resting oxygen saturations. The pulmonary exam can be normal or can reveal fine end-inspiratory crackles, and may include high-pitched, inspiratory rhonchi, or “squeaks.”1
When a diagnosis of ILD is suspected, investigation should begin with high-resolution CT (HRCT).1.3-5 In patients for whom a potential cause of ILD is not identified or who have more than one potential cause, specific patterns seen on the HRCT can help determine the most likely etiology.5 Chest x-ray has low sensitivity and specificity for ILD and can frequently be misinterpreted, as occurred with our patient.1
Rule out other causes of dyspnea
The differential diagnosis for dyspnea includes:
Heart failure. Congestive heart failure can present with acutely worsening dyspnea and cough, but is also commonly associated with orthopnea and/or paroxysmal nocturnal dyspnea. On physical examination, findings of volume overload such as pulmonary crackles, lower extremity edema, and elevated jugular venous pressure are additional signs that heart failure is present.
Pulmonary embolism (PE). Patients with PE commonly present with acute dyspnea, chest pain, and may also have a cough. Additional risk factors for PE (prolonged immobility, fracture, recent hospitalization) may also be present. A Wells score and a D-dimer test can be used to determine the probability of a patient having PE.
Asthma/chronic obstructive pulmonary disease. COPD exacerbations commonly present with a productive cough and worsening dyspnea. Pulmonary exam findings include wheezing, tachypnea, increased respiratory effort, and poor air movement.
Infection (including coccidioidomycosis in the desert southwest, where this patient lived). Our patient was initially treated for pneumonia because she had reported fevers associated with dyspnea and cough along with an elevated white blood cell count. Chest x-ray findings in patients with pneumonia can reveal either lobar consolidation or interstitial infiltrates.
Failure to respond to treatment of the more common causes of dyspnea, as occurred with our patient, should prompt consideration of ILD, particularly in those who have a history of connective tissue disease. Once a diagnosis of ILD is made, referral to a pulmonary specialist is advised.1,3
A poor prognosis and a focus on quality of life
Immunosuppressive therapy is currently the standard treatment for ILD, although there is little evidence to support this practice.1,3,4 Therapy usually includes corticosteroids with or without the addition of a second immunosuppressive agent such as azathioprine, mycophenolate mofetil, or cyclophosphamide.1,4
In addition to drug therapy, the American College of Chest Physicians recommends routine assessment of quality-of-life (QOL) concerns in patients with ILD (TABLE).6,7 Additional QOL tools available to physicians include the Medical Outcomes Study Short-Form 36-Item Instrument8 and the St. George’s Respiratory Questionnaire.9
The prognosis is poor, even with treatment. Patients with ILD have a life expectancy that averages 2 to 4 years from diagnosis.6 Patients with ILD are frequently distressed about worsening control of dyspnea and becoming a burden to family members; they also have anxiety about dying.6 It’s important to allocate sufficient time for end-of-life discussions, as studies have shown that patients would like their physicians to address the issue more thoroughly.10
Our patient was started on high-flow oxygen and high-dose steroids. Azathioprine was later added. The patient’s methotrexate was stopped, in light of its association with ILD. Unfortunately, the treatments were not successful and the patient’s respiratory status continued to deteriorate. A family meeting was held with the patient to discuss end-of-life wishes, and the patient expressed a preference for hospice care. She died a few days after hospice enrollment.
CORRESPONDENCE
Karyn B. Kolman, MD, University of Arizona College of Medicine at South Campus Family Medicine Residency, 2800 E Ajo Way, Room 3006, Tucson, AZ 85713; [email protected].
1. Wallis A, Spinks K. The diagnosis and management of interstial lung disease. BMJ. 2015;350:h2072.
2. Raghu G, Chen SY, Hou Q, et al. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old. Eur Respir J. 2016;48:179-186.
3. Yunt ZX, Solomon JJ. Lung disease in rheumatoid arthritis. Rheum Dis Clin North Am. 2015;41:225-236.
4. Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013;143:814-824.
5. Nair A, Walsh SL, Desai SR. Imaging of pulmonary involvement in rheumatic disease. Rheum Dis Clin North Am. 2015;41:167-196.
6. Gilbert CR, Smith CM. Advanced parenchymal lung disease: quality of life and palliative care. Mt Sinai J Med. 2009;76:63-70.
7. Swigris JJ, Stewart AL, Gould MK, et al. Patients’ perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives. Health Qual Life Outcomes. 2005;3:61.
8. RAND. Medical Outcomes Study 36-Item Short Form Survey (SF-36). Available at: http://www.rand.org/health/surveys_tools/mos/mos_core_36item.html. Accessed May 27, 2016.
9. St George’s Respiratory Questionnaire. Available at: http://www.healthstatus.sgul.ac.uk/. Accessed May 27, 2016.
10. Bajwah S, Koffman J, Higginson IJ, et. al. ‘I wish I knew more…’ the end-of-life planning and information needs for end-stage fibrotic interstitial lung disease: views of patients, carers, and health professionals. BMJ Support Palliat Care. 2013;3;84-90.
A 62-year-old woman presented with a 2- to 3-week history of fatigue, nonproductive cough, dyspnea on exertion, and intermittent fever/chills. Her past medical history was significant for rheumatoid arthritis (RA) that had been treated with methotrexate and prednisone for the past 6 years. The patient was currently smoking half a pack a day with a 40-pack year history. The patient was a lifelong resident of Arizona and had previously worked in a stone mine.
On physical examination she appeared comfortable without any increased work of breathing. Her vital signs included a temperature of 36.6° C, a blood pressure of 110/54 mm Hg, a pulse of 90 beats/min, respirations of 16/min, and room-air oxygen saturation of 87%. Pulmonary examination revealed scattered wheezes with fine bibasilar crackles. The remainder of her physical exam was normal. Because she was hypoxic, she was admitted to the hospital.
At the hospital, a chest x-ray showed diffuse, bilateral interstitial changes (FIGURE 1). Laboratory tests revealed a white blood cell count of 13,800/mcL (normal: 4500-10,500/mcL) with 73% neutrophils (normal: 40%-60%), 3% bands (normal: 0-3%), 14% monocytes (normal: 2%-8%), 6% eosinophils (normal: 1%-4%), and 3% lymphocytes (normal: 20%-30%). Community-acquired pneumonia was suspected, and the patient was started on levofloxacin. Over the next 2 days, her dyspnea worsened. She became tachycardic, and her oxygen requirement increased to 15 L/min via a non-rebreather mask. She was transferred to the intensive care unit.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Interstitial lung disease
Given the patient’s worsening respiratory status, a computed tomography (CT) scan was ordered (FIGURE 2). Review of the CT scan showed ground-glass opacification, mild subpleural honeycombing, reticularity, and traction bronchiectasis bilaterally at the lung bases. Bronchoscopy with lavage was performed to rule out infectious etiologies and was negative. These findings, along with the patient’s medical history of RA and use of methotrexate, led us to diagnose interstitial lung disease (ILD) in this patient.
ILD refers to a group of disorders that primarily affects the pulmonary interstitium, rather than the alveolar spaces or pleura.1 The most common causes of ILD seen in primary care are idiopathic pulmonary fibrosis, connective tissue disease, and hypersensitivity pneumonitis secondary to drugs (such as methotrexate, citalopram, fluoxetine, nitrofurantoin, and cephalosporins), radiation, or occupational exposures. (Textile, metal, and plastic workers are at a heightened risk, as are painters and individuals who work with animals.)1 In 2010, idiopathic pulmonary fibrosis had a prevalence of 18.2 cases per 100,000 people.2 Determining the underlying cause of ILD is important, as it may influence prognosis and treatment decisions.
The most common presenting symptoms of ILD are exertional dyspnea, cough with insidious onset, fatigue, and weakness.1,3 Bear in mind, however, that patients with ILD associated with a connective tissue disease may have more subtle manifestations of exertional dyspnea, such as a change in activity level or low resting oxygen saturations. The pulmonary exam can be normal or can reveal fine end-inspiratory crackles, and may include high-pitched, inspiratory rhonchi, or “squeaks.”1
When a diagnosis of ILD is suspected, investigation should begin with high-resolution CT (HRCT).1.3-5 In patients for whom a potential cause of ILD is not identified or who have more than one potential cause, specific patterns seen on the HRCT can help determine the most likely etiology.5 Chest x-ray has low sensitivity and specificity for ILD and can frequently be misinterpreted, as occurred with our patient.1
Rule out other causes of dyspnea
The differential diagnosis for dyspnea includes:
Heart failure. Congestive heart failure can present with acutely worsening dyspnea and cough, but is also commonly associated with orthopnea and/or paroxysmal nocturnal dyspnea. On physical examination, findings of volume overload such as pulmonary crackles, lower extremity edema, and elevated jugular venous pressure are additional signs that heart failure is present.
Pulmonary embolism (PE). Patients with PE commonly present with acute dyspnea, chest pain, and may also have a cough. Additional risk factors for PE (prolonged immobility, fracture, recent hospitalization) may also be present. A Wells score and a D-dimer test can be used to determine the probability of a patient having PE.
Asthma/chronic obstructive pulmonary disease. COPD exacerbations commonly present with a productive cough and worsening dyspnea. Pulmonary exam findings include wheezing, tachypnea, increased respiratory effort, and poor air movement.
Infection (including coccidioidomycosis in the desert southwest, where this patient lived). Our patient was initially treated for pneumonia because she had reported fevers associated with dyspnea and cough along with an elevated white blood cell count. Chest x-ray findings in patients with pneumonia can reveal either lobar consolidation or interstitial infiltrates.
Failure to respond to treatment of the more common causes of dyspnea, as occurred with our patient, should prompt consideration of ILD, particularly in those who have a history of connective tissue disease. Once a diagnosis of ILD is made, referral to a pulmonary specialist is advised.1,3
A poor prognosis and a focus on quality of life
Immunosuppressive therapy is currently the standard treatment for ILD, although there is little evidence to support this practice.1,3,4 Therapy usually includes corticosteroids with or without the addition of a second immunosuppressive agent such as azathioprine, mycophenolate mofetil, or cyclophosphamide.1,4
In addition to drug therapy, the American College of Chest Physicians recommends routine assessment of quality-of-life (QOL) concerns in patients with ILD (TABLE).6,7 Additional QOL tools available to physicians include the Medical Outcomes Study Short-Form 36-Item Instrument8 and the St. George’s Respiratory Questionnaire.9
The prognosis is poor, even with treatment. Patients with ILD have a life expectancy that averages 2 to 4 years from diagnosis.6 Patients with ILD are frequently distressed about worsening control of dyspnea and becoming a burden to family members; they also have anxiety about dying.6 It’s important to allocate sufficient time for end-of-life discussions, as studies have shown that patients would like their physicians to address the issue more thoroughly.10
Our patient was started on high-flow oxygen and high-dose steroids. Azathioprine was later added. The patient’s methotrexate was stopped, in light of its association with ILD. Unfortunately, the treatments were not successful and the patient’s respiratory status continued to deteriorate. A family meeting was held with the patient to discuss end-of-life wishes, and the patient expressed a preference for hospice care. She died a few days after hospice enrollment.
CORRESPONDENCE
Karyn B. Kolman, MD, University of Arizona College of Medicine at South Campus Family Medicine Residency, 2800 E Ajo Way, Room 3006, Tucson, AZ 85713; [email protected].
A 62-year-old woman presented with a 2- to 3-week history of fatigue, nonproductive cough, dyspnea on exertion, and intermittent fever/chills. Her past medical history was significant for rheumatoid arthritis (RA) that had been treated with methotrexate and prednisone for the past 6 years. The patient was currently smoking half a pack a day with a 40-pack year history. The patient was a lifelong resident of Arizona and had previously worked in a stone mine.
On physical examination she appeared comfortable without any increased work of breathing. Her vital signs included a temperature of 36.6° C, a blood pressure of 110/54 mm Hg, a pulse of 90 beats/min, respirations of 16/min, and room-air oxygen saturation of 87%. Pulmonary examination revealed scattered wheezes with fine bibasilar crackles. The remainder of her physical exam was normal. Because she was hypoxic, she was admitted to the hospital.
At the hospital, a chest x-ray showed diffuse, bilateral interstitial changes (FIGURE 1). Laboratory tests revealed a white blood cell count of 13,800/mcL (normal: 4500-10,500/mcL) with 73% neutrophils (normal: 40%-60%), 3% bands (normal: 0-3%), 14% monocytes (normal: 2%-8%), 6% eosinophils (normal: 1%-4%), and 3% lymphocytes (normal: 20%-30%). Community-acquired pneumonia was suspected, and the patient was started on levofloxacin. Over the next 2 days, her dyspnea worsened. She became tachycardic, and her oxygen requirement increased to 15 L/min via a non-rebreather mask. She was transferred to the intensive care unit.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Interstitial lung disease
Given the patient’s worsening respiratory status, a computed tomography (CT) scan was ordered (FIGURE 2). Review of the CT scan showed ground-glass opacification, mild subpleural honeycombing, reticularity, and traction bronchiectasis bilaterally at the lung bases. Bronchoscopy with lavage was performed to rule out infectious etiologies and was negative. These findings, along with the patient’s medical history of RA and use of methotrexate, led us to diagnose interstitial lung disease (ILD) in this patient.
ILD refers to a group of disorders that primarily affects the pulmonary interstitium, rather than the alveolar spaces or pleura.1 The most common causes of ILD seen in primary care are idiopathic pulmonary fibrosis, connective tissue disease, and hypersensitivity pneumonitis secondary to drugs (such as methotrexate, citalopram, fluoxetine, nitrofurantoin, and cephalosporins), radiation, or occupational exposures. (Textile, metal, and plastic workers are at a heightened risk, as are painters and individuals who work with animals.)1 In 2010, idiopathic pulmonary fibrosis had a prevalence of 18.2 cases per 100,000 people.2 Determining the underlying cause of ILD is important, as it may influence prognosis and treatment decisions.
The most common presenting symptoms of ILD are exertional dyspnea, cough with insidious onset, fatigue, and weakness.1,3 Bear in mind, however, that patients with ILD associated with a connective tissue disease may have more subtle manifestations of exertional dyspnea, such as a change in activity level or low resting oxygen saturations. The pulmonary exam can be normal or can reveal fine end-inspiratory crackles, and may include high-pitched, inspiratory rhonchi, or “squeaks.”1
When a diagnosis of ILD is suspected, investigation should begin with high-resolution CT (HRCT).1.3-5 In patients for whom a potential cause of ILD is not identified or who have more than one potential cause, specific patterns seen on the HRCT can help determine the most likely etiology.5 Chest x-ray has low sensitivity and specificity for ILD and can frequently be misinterpreted, as occurred with our patient.1
Rule out other causes of dyspnea
The differential diagnosis for dyspnea includes:
Heart failure. Congestive heart failure can present with acutely worsening dyspnea and cough, but is also commonly associated with orthopnea and/or paroxysmal nocturnal dyspnea. On physical examination, findings of volume overload such as pulmonary crackles, lower extremity edema, and elevated jugular venous pressure are additional signs that heart failure is present.
Pulmonary embolism (PE). Patients with PE commonly present with acute dyspnea, chest pain, and may also have a cough. Additional risk factors for PE (prolonged immobility, fracture, recent hospitalization) may also be present. A Wells score and a D-dimer test can be used to determine the probability of a patient having PE.
Asthma/chronic obstructive pulmonary disease. COPD exacerbations commonly present with a productive cough and worsening dyspnea. Pulmonary exam findings include wheezing, tachypnea, increased respiratory effort, and poor air movement.
Infection (including coccidioidomycosis in the desert southwest, where this patient lived). Our patient was initially treated for pneumonia because she had reported fevers associated with dyspnea and cough along with an elevated white blood cell count. Chest x-ray findings in patients with pneumonia can reveal either lobar consolidation or interstitial infiltrates.
Failure to respond to treatment of the more common causes of dyspnea, as occurred with our patient, should prompt consideration of ILD, particularly in those who have a history of connective tissue disease. Once a diagnosis of ILD is made, referral to a pulmonary specialist is advised.1,3
A poor prognosis and a focus on quality of life
Immunosuppressive therapy is currently the standard treatment for ILD, although there is little evidence to support this practice.1,3,4 Therapy usually includes corticosteroids with or without the addition of a second immunosuppressive agent such as azathioprine, mycophenolate mofetil, or cyclophosphamide.1,4
In addition to drug therapy, the American College of Chest Physicians recommends routine assessment of quality-of-life (QOL) concerns in patients with ILD (TABLE).6,7 Additional QOL tools available to physicians include the Medical Outcomes Study Short-Form 36-Item Instrument8 and the St. George’s Respiratory Questionnaire.9
The prognosis is poor, even with treatment. Patients with ILD have a life expectancy that averages 2 to 4 years from diagnosis.6 Patients with ILD are frequently distressed about worsening control of dyspnea and becoming a burden to family members; they also have anxiety about dying.6 It’s important to allocate sufficient time for end-of-life discussions, as studies have shown that patients would like their physicians to address the issue more thoroughly.10
Our patient was started on high-flow oxygen and high-dose steroids. Azathioprine was later added. The patient’s methotrexate was stopped, in light of its association with ILD. Unfortunately, the treatments were not successful and the patient’s respiratory status continued to deteriorate. A family meeting was held with the patient to discuss end-of-life wishes, and the patient expressed a preference for hospice care. She died a few days after hospice enrollment.
CORRESPONDENCE
Karyn B. Kolman, MD, University of Arizona College of Medicine at South Campus Family Medicine Residency, 2800 E Ajo Way, Room 3006, Tucson, AZ 85713; [email protected].
1. Wallis A, Spinks K. The diagnosis and management of interstial lung disease. BMJ. 2015;350:h2072.
2. Raghu G, Chen SY, Hou Q, et al. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old. Eur Respir J. 2016;48:179-186.
3. Yunt ZX, Solomon JJ. Lung disease in rheumatoid arthritis. Rheum Dis Clin North Am. 2015;41:225-236.
4. Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013;143:814-824.
5. Nair A, Walsh SL, Desai SR. Imaging of pulmonary involvement in rheumatic disease. Rheum Dis Clin North Am. 2015;41:167-196.
6. Gilbert CR, Smith CM. Advanced parenchymal lung disease: quality of life and palliative care. Mt Sinai J Med. 2009;76:63-70.
7. Swigris JJ, Stewart AL, Gould MK, et al. Patients’ perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives. Health Qual Life Outcomes. 2005;3:61.
8. RAND. Medical Outcomes Study 36-Item Short Form Survey (SF-36). Available at: http://www.rand.org/health/surveys_tools/mos/mos_core_36item.html. Accessed May 27, 2016.
9. St George’s Respiratory Questionnaire. Available at: http://www.healthstatus.sgul.ac.uk/. Accessed May 27, 2016.
10. Bajwah S, Koffman J, Higginson IJ, et. al. ‘I wish I knew more…’ the end-of-life planning and information needs for end-stage fibrotic interstitial lung disease: views of patients, carers, and health professionals. BMJ Support Palliat Care. 2013;3;84-90.
1. Wallis A, Spinks K. The diagnosis and management of interstial lung disease. BMJ. 2015;350:h2072.
2. Raghu G, Chen SY, Hou Q, et al. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old. Eur Respir J. 2016;48:179-186.
3. Yunt ZX, Solomon JJ. Lung disease in rheumatoid arthritis. Rheum Dis Clin North Am. 2015;41:225-236.
4. Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest. 2013;143:814-824.
5. Nair A, Walsh SL, Desai SR. Imaging of pulmonary involvement in rheumatic disease. Rheum Dis Clin North Am. 2015;41:167-196.
6. Gilbert CR, Smith CM. Advanced parenchymal lung disease: quality of life and palliative care. Mt Sinai J Med. 2009;76:63-70.
7. Swigris JJ, Stewart AL, Gould MK, et al. Patients’ perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives. Health Qual Life Outcomes. 2005;3:61.
8. RAND. Medical Outcomes Study 36-Item Short Form Survey (SF-36). Available at: http://www.rand.org/health/surveys_tools/mos/mos_core_36item.html. Accessed May 27, 2016.
9. St George’s Respiratory Questionnaire. Available at: http://www.healthstatus.sgul.ac.uk/. Accessed May 27, 2016.
10. Bajwah S, Koffman J, Higginson IJ, et. al. ‘I wish I knew more…’ the end-of-life planning and information needs for end-stage fibrotic interstitial lung disease: views of patients, carers, and health professionals. BMJ Support Palliat Care. 2013;3;84-90.
Tamsulosin for patients with ureteral stones?
ILLUSTRATIVE CASE
A 54-year-old man presents to the emergency department (ED) with acute onset left flank pain that radiates to the groin. A computed tomography (CT) scan of the abdomen/pelvis without contrast reveals a 7-mm distal ureteral stone. He is deemed appropriate for outpatient management. In addition to pain medications, should you prescribe tamsulosin?
According to the most recent National Health and Nutrition Examination Survey, the population prevalence of kidney stones is 8.8% with a self-reported prevalence in men of 10.6% and a self-reported prevalence in women of 7.1%.2 Most ureteral stones can be treated in the outpatient setting with oral hydration, antiemetics, and pain control with nonsteroidal anti-inflammatory medications as first-line treatment and opioids as a second-line option.3 In addition, alpha-blockers are used for medical expulsive therapy (MET). In fact, the European Association of Urology guideline on urolithiasis states that MET may accelerate passage of ureteral stones.3
Recently, however, uncertainty has surrounded the effectiveness of the alpha-blocker tamsulosin. Two systematic reviews, limited by heterogeneity because some of the studies lacked a placebo control and blinding, concluded that alpha-blockers increased stone passage within one to 6 weeks when compared with placebo or no additional therapy.4,5 However, a recent large multicenter, randomized controlled trial (RCT) revealed no difference between tamsulosin and nifedipine or either one compared with placebo at decreasing the need for further treatment to achieve stone passage within 4 weeks.6
[polldaddy:9906038]
STUDY SUMMARY
New meta-analysis breaks down results by stone size
This meta-analysis by Wang et al, consisting of 8 randomized, double-blind, placebo-controlled trials of adult patients (N=1384), examined the effect of oral tamsulosin 0.4 mg/d (average of a 28-day course) on distal ureteral stone passage.1 A subgroup analysis comparing stone size (<5 mm and 5-10 mm) was also conducted to determine if stone size modified the effect of tamsulosin.
Although the initial search included studies published between 1966 and 2015, the 8 that were eventually analyzed were published between 2009 and 2015, were conducted in multiple countries (and included regardless of language), and were conducted in ED and outpatient urology settings. The main outcome measure was the risk difference in stone passage between the tamsulosin group and placebo group after follow-up imaging at 3 weeks with CT or plain film radiographs.
Tamsulosin helps some, but not all. The pooled risk of stone passage was higher in the tamsulosin group than in the placebo group (85% vs 66%; risk difference [RD]=17%; 95% confidence interval [CI], 6%-27%), but significant heterogeneity existed across the trials (I2=80.2%). After subgroup analysis by stone size, the researchers found that tamsulosin was beneficial for larger stones, 5 to 10 mm in size (6 trials, N=514; RD=22%; 95% CI, 12%-33%; number needed to treat=5), compared with placebo, but not for smaller stones, <5 mm in size (4 trials, N=533; RD=-0.3%; 95% CI, -4% to 3%). The measure of heterogeneity in the 5- to 10-mm subgroup demonstrated a less heterogeneous population of studies (I2=33%) than that for the <5-mm subgroup (I2=0%).
In terms of adverse events, tamsulosin did not increase the risk of dizziness (RD=.2%; 95% CI, -2.1% to 2.5%) or postural hypotension (RD=.1%; 95% CI, -0.4% to 0.5%) compared with placebo.
WHAT’S NEW
Passage of larger stones increases with tamsulosin
This meta-analysis included only randomized, double-blind, placebo-controlled trials. Prior meta-analyses did not. Also, this review included the SUSPEND (Spontaneous Urinary Stone Passage Enabled by Drugs) trial, an RCT discussed in a previous PURL (Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.) that recommended against the alpha-blockers tamsulosin and nifedipine for ureteral stones measuring <10 mm.6,7
But the subgroup analysis in this more recent review went one step further in the investigation of tamsulosin’s effect by examining passage rates by stone size (<5 mm vs 5-10 mm) and revealing that passage of larger stones (5-10 mm) increased with tamsulosin. The different results based on stone size may explain the recent uncertainty as to whether tamsulosin improves the rate of stone passage.
CAVEATS
Study doesn’t address proximal, or extra-large stones
Only distal stones were included in 7 of the 8 trials. Thus, this meta-analysis was unable to determine the effect on more proximal stones. Also, it’s unclear if the drug provides any benefit with stones >10 mm in size.
CHALLENGES TO IMPLEMENTATION
None worth mentioning
We see no challenges to implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Wang RC, Smith-Bindman R, Whitaker E, et al. Effect of tamsulosin on stone passage for ureteral stones: a systematic review and meta-analysis. Ann Emerg Med. 2017;69:353-361.
2. Scales CD Jr, Smith AC, Hanley JM, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.
3. Türk C, Petrik A, Sarica K, et al. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol. 2016;69:468-474.
4. Hollingsworth JM, Canales BK, Rogers MAM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016;355:i6112.
5. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014:CD008509.
6. Pickard R, Starr K, MacLennan G, et al. Medical expulsion therapy in adults with ureteric colic: a multicentre, randomized, placebo-controlled trial. Lancet. 2015;386:341-349.
7. Slattengren AH, Prasad S, Jarrett JB. Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.
ILLUSTRATIVE CASE
A 54-year-old man presents to the emergency department (ED) with acute onset left flank pain that radiates to the groin. A computed tomography (CT) scan of the abdomen/pelvis without contrast reveals a 7-mm distal ureteral stone. He is deemed appropriate for outpatient management. In addition to pain medications, should you prescribe tamsulosin?
According to the most recent National Health and Nutrition Examination Survey, the population prevalence of kidney stones is 8.8% with a self-reported prevalence in men of 10.6% and a self-reported prevalence in women of 7.1%.2 Most ureteral stones can be treated in the outpatient setting with oral hydration, antiemetics, and pain control with nonsteroidal anti-inflammatory medications as first-line treatment and opioids as a second-line option.3 In addition, alpha-blockers are used for medical expulsive therapy (MET). In fact, the European Association of Urology guideline on urolithiasis states that MET may accelerate passage of ureteral stones.3
Recently, however, uncertainty has surrounded the effectiveness of the alpha-blocker tamsulosin. Two systematic reviews, limited by heterogeneity because some of the studies lacked a placebo control and blinding, concluded that alpha-blockers increased stone passage within one to 6 weeks when compared with placebo or no additional therapy.4,5 However, a recent large multicenter, randomized controlled trial (RCT) revealed no difference between tamsulosin and nifedipine or either one compared with placebo at decreasing the need for further treatment to achieve stone passage within 4 weeks.6
[polldaddy:9906038]
STUDY SUMMARY
New meta-analysis breaks down results by stone size
This meta-analysis by Wang et al, consisting of 8 randomized, double-blind, placebo-controlled trials of adult patients (N=1384), examined the effect of oral tamsulosin 0.4 mg/d (average of a 28-day course) on distal ureteral stone passage.1 A subgroup analysis comparing stone size (<5 mm and 5-10 mm) was also conducted to determine if stone size modified the effect of tamsulosin.
Although the initial search included studies published between 1966 and 2015, the 8 that were eventually analyzed were published between 2009 and 2015, were conducted in multiple countries (and included regardless of language), and were conducted in ED and outpatient urology settings. The main outcome measure was the risk difference in stone passage between the tamsulosin group and placebo group after follow-up imaging at 3 weeks with CT or plain film radiographs.
Tamsulosin helps some, but not all. The pooled risk of stone passage was higher in the tamsulosin group than in the placebo group (85% vs 66%; risk difference [RD]=17%; 95% confidence interval [CI], 6%-27%), but significant heterogeneity existed across the trials (I2=80.2%). After subgroup analysis by stone size, the researchers found that tamsulosin was beneficial for larger stones, 5 to 10 mm in size (6 trials, N=514; RD=22%; 95% CI, 12%-33%; number needed to treat=5), compared with placebo, but not for smaller stones, <5 mm in size (4 trials, N=533; RD=-0.3%; 95% CI, -4% to 3%). The measure of heterogeneity in the 5- to 10-mm subgroup demonstrated a less heterogeneous population of studies (I2=33%) than that for the <5-mm subgroup (I2=0%).
In terms of adverse events, tamsulosin did not increase the risk of dizziness (RD=.2%; 95% CI, -2.1% to 2.5%) or postural hypotension (RD=.1%; 95% CI, -0.4% to 0.5%) compared with placebo.
WHAT’S NEW
Passage of larger stones increases with tamsulosin
This meta-analysis included only randomized, double-blind, placebo-controlled trials. Prior meta-analyses did not. Also, this review included the SUSPEND (Spontaneous Urinary Stone Passage Enabled by Drugs) trial, an RCT discussed in a previous PURL (Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.) that recommended against the alpha-blockers tamsulosin and nifedipine for ureteral stones measuring <10 mm.6,7
But the subgroup analysis in this more recent review went one step further in the investigation of tamsulosin’s effect by examining passage rates by stone size (<5 mm vs 5-10 mm) and revealing that passage of larger stones (5-10 mm) increased with tamsulosin. The different results based on stone size may explain the recent uncertainty as to whether tamsulosin improves the rate of stone passage.
CAVEATS
Study doesn’t address proximal, or extra-large stones
Only distal stones were included in 7 of the 8 trials. Thus, this meta-analysis was unable to determine the effect on more proximal stones. Also, it’s unclear if the drug provides any benefit with stones >10 mm in size.
CHALLENGES TO IMPLEMENTATION
None worth mentioning
We see no challenges to implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 54-year-old man presents to the emergency department (ED) with acute onset left flank pain that radiates to the groin. A computed tomography (CT) scan of the abdomen/pelvis without contrast reveals a 7-mm distal ureteral stone. He is deemed appropriate for outpatient management. In addition to pain medications, should you prescribe tamsulosin?
According to the most recent National Health and Nutrition Examination Survey, the population prevalence of kidney stones is 8.8% with a self-reported prevalence in men of 10.6% and a self-reported prevalence in women of 7.1%.2 Most ureteral stones can be treated in the outpatient setting with oral hydration, antiemetics, and pain control with nonsteroidal anti-inflammatory medications as first-line treatment and opioids as a second-line option.3 In addition, alpha-blockers are used for medical expulsive therapy (MET). In fact, the European Association of Urology guideline on urolithiasis states that MET may accelerate passage of ureteral stones.3
Recently, however, uncertainty has surrounded the effectiveness of the alpha-blocker tamsulosin. Two systematic reviews, limited by heterogeneity because some of the studies lacked a placebo control and blinding, concluded that alpha-blockers increased stone passage within one to 6 weeks when compared with placebo or no additional therapy.4,5 However, a recent large multicenter, randomized controlled trial (RCT) revealed no difference between tamsulosin and nifedipine or either one compared with placebo at decreasing the need for further treatment to achieve stone passage within 4 weeks.6
[polldaddy:9906038]
STUDY SUMMARY
New meta-analysis breaks down results by stone size
This meta-analysis by Wang et al, consisting of 8 randomized, double-blind, placebo-controlled trials of adult patients (N=1384), examined the effect of oral tamsulosin 0.4 mg/d (average of a 28-day course) on distal ureteral stone passage.1 A subgroup analysis comparing stone size (<5 mm and 5-10 mm) was also conducted to determine if stone size modified the effect of tamsulosin.
Although the initial search included studies published between 1966 and 2015, the 8 that were eventually analyzed were published between 2009 and 2015, were conducted in multiple countries (and included regardless of language), and were conducted in ED and outpatient urology settings. The main outcome measure was the risk difference in stone passage between the tamsulosin group and placebo group after follow-up imaging at 3 weeks with CT or plain film radiographs.
Tamsulosin helps some, but not all. The pooled risk of stone passage was higher in the tamsulosin group than in the placebo group (85% vs 66%; risk difference [RD]=17%; 95% confidence interval [CI], 6%-27%), but significant heterogeneity existed across the trials (I2=80.2%). After subgroup analysis by stone size, the researchers found that tamsulosin was beneficial for larger stones, 5 to 10 mm in size (6 trials, N=514; RD=22%; 95% CI, 12%-33%; number needed to treat=5), compared with placebo, but not for smaller stones, <5 mm in size (4 trials, N=533; RD=-0.3%; 95% CI, -4% to 3%). The measure of heterogeneity in the 5- to 10-mm subgroup demonstrated a less heterogeneous population of studies (I2=33%) than that for the <5-mm subgroup (I2=0%).
In terms of adverse events, tamsulosin did not increase the risk of dizziness (RD=.2%; 95% CI, -2.1% to 2.5%) or postural hypotension (RD=.1%; 95% CI, -0.4% to 0.5%) compared with placebo.
WHAT’S NEW
Passage of larger stones increases with tamsulosin
This meta-analysis included only randomized, double-blind, placebo-controlled trials. Prior meta-analyses did not. Also, this review included the SUSPEND (Spontaneous Urinary Stone Passage Enabled by Drugs) trial, an RCT discussed in a previous PURL (Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.) that recommended against the alpha-blockers tamsulosin and nifedipine for ureteral stones measuring <10 mm.6,7
But the subgroup analysis in this more recent review went one step further in the investigation of tamsulosin’s effect by examining passage rates by stone size (<5 mm vs 5-10 mm) and revealing that passage of larger stones (5-10 mm) increased with tamsulosin. The different results based on stone size may explain the recent uncertainty as to whether tamsulosin improves the rate of stone passage.
CAVEATS
Study doesn’t address proximal, or extra-large stones
Only distal stones were included in 7 of the 8 trials. Thus, this meta-analysis was unable to determine the effect on more proximal stones. Also, it’s unclear if the drug provides any benefit with stones >10 mm in size.
CHALLENGES TO IMPLEMENTATION
None worth mentioning
We see no challenges to implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Wang RC, Smith-Bindman R, Whitaker E, et al. Effect of tamsulosin on stone passage for ureteral stones: a systematic review and meta-analysis. Ann Emerg Med. 2017;69:353-361.
2. Scales CD Jr, Smith AC, Hanley JM, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.
3. Türk C, Petrik A, Sarica K, et al. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol. 2016;69:468-474.
4. Hollingsworth JM, Canales BK, Rogers MAM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016;355:i6112.
5. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014:CD008509.
6. Pickard R, Starr K, MacLennan G, et al. Medical expulsion therapy in adults with ureteric colic: a multicentre, randomized, placebo-controlled trial. Lancet. 2015;386:341-349.
7. Slattengren AH, Prasad S, Jarrett JB. Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.
1. Wang RC, Smith-Bindman R, Whitaker E, et al. Effect of tamsulosin on stone passage for ureteral stones: a systematic review and meta-analysis. Ann Emerg Med. 2017;69:353-361.
2. Scales CD Jr, Smith AC, Hanley JM, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.
3. Türk C, Petrik A, Sarica K, et al. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol. 2016;69:468-474.
4. Hollingsworth JM, Canales BK, Rogers MAM, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016;355:i6112.
5. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014:CD008509.
6. Pickard R, Starr K, MacLennan G, et al. Medical expulsion therapy in adults with ureteric colic: a multicentre, randomized, placebo-controlled trial. Lancet. 2015;386:341-349.
7. Slattengren AH, Prasad S, Jarrett JB. Kidney stones? It’s time to rethink those meds. J Fam Pract. 2016;65:118-120.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
PRACTICE CHANGER
Prescribe tamsulosin for stone expulsion in patients with distal ureteral stones 5 to 10 mm in size.1
STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of randomized controlled trials.
Wang RC, Smith-Bindman R, Whitaker E, et al. Effect of tamsulosin on stone passage for ureteral stones: a systematic review and meta-analysis. Ann Emerg Med. 2017;69:353-361.
CDC provides advice on recent hepatitis A outbreaks
The epidemiology of hepatitis A virus (HAV) disease has changed. Since July 2016, there have been 5 large outbreaks of infection involving more than 1600 cases,1 with affected states requiring assistance from the Centers for Disease Control and Prevention (CDC). Two of these outbreaks were foodborne, and 3 involved person-to-person transmission.1
Before 2016, the number of outbreaks had been very low, and were predominantly associated with contaminated food, infected food handlers, and other food service-related exposures. Total annual cases of HAV infection had been declining steadily in all age groups since 1995 when HAV vaccine became available, from an estimated 271,000 cases resulting in 100 deaths2 to an estimated 2800 cases (with 1390 reported) resulting in 67 deaths in 2015 (FIGURE).3
Extent of the outbreaks
The largest hepatitis A outbreak involving person-to-person transmission in the United States in the past 20 years is occurring now in California. Predominantly affected are the homeless and users of illicit drugs, whose risk of infection is compounded by exposure to fecally-contaminated environments. As of December 1, the largest number of cases were recorded in San Diego (567), Santa Cruz (76), and Los Angeles (11).4 Adding 18 cases from other locations, the total has reached 672, resulting in 430 hospitalizations (64%) and 21 deaths (3%).4 In San Diego, 20% of those infected also had chronic hepatitis C and 5% had chronic hepatitis B.1
In southeastern Michigan, 555 cases have been reported, with 457 hospitalizations (82%) and 20 deaths (4%).5 In Utah, 91 cases and 53 hospitalizations (58%) have been documented.6 In these regions, the predominant risk factors have been homelessness and illicit drug use. And many of those infected have had chronic hepatitis C (27.5%), hepatitis B (13.2%), or both (9.9%).6 In 2 of the 3 states just described, the outbreaks have involved HAV genotype 1B.1
In New York City, an outbreak starting in January 2017 resulted in 51 cases. The epidemiology of this outbreak has been different from the others, involving men who have sex with men (MSM) and the HAV genotype 1A that matches a strain circulating among MSM in Europe.7
Low adult immunity is behind the outbreaks
These outbreaks have occurred in an adult US population that has low levels of immunity to HAV. In 2012 only 12.2% of adults ages 19 to 49 years had received 2 doses of HAV vaccine8 and only 24.2% of adults had antibodies to HAV,9 showing that most adults had never been infected with the virus or vaccinated. The reduction in HAV incidence previously described is due to the introduction of targeted, and then universal, child HAV vaccination recommendations by the Advisory Committee on Immunization Practices.
As the incidence of HAV disease declined, fewer individuals became infected as children, leading later to a susceptible pool of adults who had not been infected as children and who did not receive the vaccine in adulthood. Most of these adults will not be exposed to HAV due to decreased rates of infection in children, which, historically, has been the predominant means of adult exposure. The high hospitalization and death rates encountered in the recent and ongoing large outbreaks are explained by the multiple comorbidities of those infected.
Who should be vaccinated against HAV
The CDC recommends giving HAV vaccine to all children at age one year, and to the following groups:2,10,11
- residents of a community that has a high rate of hepatitis A infection
- household members or other close personal contacts (eg, regular babysitters) of adopted children newly arrived from countries with high or intermediate hepatitis A endemicity
- men who have sex with other men
- users of illicit injection and noninjection drugs
- workers in, or travelers to, countries with high rates of hepatitis A infection
- individuals with chronic liver disease
- individuals who work with HAV-infected animals or with HAV in a research setting.
Outbreak-specific vaccine recommendations
The CDC has additionally recommended that, during outbreaks, health care providers should consider taking the following 4 steps:12,13
- Increase the availability of HAV vaccine to the homeless and to those who use illicit drugs; to anyone who has ongoing, close contact with people who are homeless or who use injection and non-injection drugs; and as post-exposure prophylaxis for unvaccinated people who have been exposed to HAV in the previous 2 weeks.
- Defer the second dose of HAV vaccine if it is in short supply.
- Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
- Use TWINRIX if other HAV vaccines are unavailable, keeping in mind that a single dose of TWINRIX achieves 94% protection against HAV but only 31% against hepatitis B virus (HBV). Three doses of TWINRIX are needed for full protection against HBV.
Available vaccines
Three vaccines are available for protection against HAV (TABLE2,14). Post-exposure prevention of HAV can be achieved with HAV vaccine or immune globulin.15 Vaccine is preferred for individuals up to age 40 years and can be used for older individuals if immune globulin is unavailable.
The CDC reports that the supply of adult HAV vaccine is being strained by these large outbreaks.16 Physicians will need to stay in touch with their local public health departments regarding vaccine availability in the community and any local recommendations being made regarding vaccine administration, as well as to the status of any local HAV outbreaks.
1. Nelson N. Hepatitis A outbreaks. Presented at: Advisory Committee on Immunization Practices; October 25, 2017; Atlanta, GA. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-10/hepatitis-04-nelson.pdf. Accessed December 5, 2017.
2. CDC. Prevention of hepatitis A through passive or active immunization. Recommendations of the Advisory Committee on Immunization Practices. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm. Accessed November 28, 2017.
3. CDC. Viral hepatitis surveillance—United States, 2015. Available at: https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanceRpt.pdf. Accessed November 28, 2017.
4. California Department of Public Health. Hepatitis A outbreak in California. Available at: https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/Immunization/Hepatitis-A-Outbreak.aspx. Accessed November 28, 2017.
5. Michigan Department of Health & Human Services. Hepatitis A southeast Michigan outbreak. Available at: http://www.michigan.gov/mdhhs/0,5885,7-339-71550_2955_2976_82305_82310-447907--,00.html. Accessed November 28, 2017.
6. Utah Department of Health. Hepatitis A outbreak. Available at: http://health.utah.gov/epi/diseases/hepatitisA/HAVoutbreak_2017. Accessed November 28, 2017.
7. Latash J, Dorsinville M, Del Rosso P, et al. Notes from the field: increase in reported hepatitis A infections among men who have sex with men–New York City, January-August 2017. MMWR Morb Mortal Wkly Rep. 2017;66:999-1000.
8. CDC. Murphy TV, Denniston MM, Hill HA, et al. Progress toward eliminating hepatitis A disease in the United States. MMWR Morb Mortal Wkly Rep. 2016;65:29-41.
9. Klevens RM, Denniston MM, Jiles-Chapman RB, et al. Decreasing immunity to hepatitis A virus infection among US adults: findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012. Vaccine. 2015;33:6192-6198.
10. CDC. Vaccines and preventable diseases. Hepatitis A in-short. Available at: https://www.cdc.gov/vaccines/vpd/hepa/public/in-short-adult.html#who. Accessed November 20, 2017.
11. CDC. Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep. 2009;58:1006-1007.
12. CDC. Interim outbreak-specific guidance on hepatitis A vaccine administration. Available at: https://www.cdc.gov/hepatitis/outbreaks/InterimOutbreakGuidance-HAV-VaccineAdmin.htm. Accessed November 20, 2017.
13. CDC. 2017–Outbreaks of hepatitis A in multiple states among people who are homeless and people who use drugs. Available at: https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm. Accessed December 11, 2017.
14. CDC. Notice to readers: FDA approval of an alternate dosing schedule for a combined hepatitis A and B vaccine (Twinrix). Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5640a5.htm. Accessed December 8, 2017.
15. CDC. Update: prevention of hepatitis A after exposure to hepatitis A virus and in International Travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56:1080-1084.
16. CDC. Current vaccine shortages and delays. Available at: https://www.cdc.gov/vaccines/hcp/clinical-resources/shortages.html. Accessed November 28, 2017.
The epidemiology of hepatitis A virus (HAV) disease has changed. Since July 2016, there have been 5 large outbreaks of infection involving more than 1600 cases,1 with affected states requiring assistance from the Centers for Disease Control and Prevention (CDC). Two of these outbreaks were foodborne, and 3 involved person-to-person transmission.1
Before 2016, the number of outbreaks had been very low, and were predominantly associated with contaminated food, infected food handlers, and other food service-related exposures. Total annual cases of HAV infection had been declining steadily in all age groups since 1995 when HAV vaccine became available, from an estimated 271,000 cases resulting in 100 deaths2 to an estimated 2800 cases (with 1390 reported) resulting in 67 deaths in 2015 (FIGURE).3
Extent of the outbreaks
The largest hepatitis A outbreak involving person-to-person transmission in the United States in the past 20 years is occurring now in California. Predominantly affected are the homeless and users of illicit drugs, whose risk of infection is compounded by exposure to fecally-contaminated environments. As of December 1, the largest number of cases were recorded in San Diego (567), Santa Cruz (76), and Los Angeles (11).4 Adding 18 cases from other locations, the total has reached 672, resulting in 430 hospitalizations (64%) and 21 deaths (3%).4 In San Diego, 20% of those infected also had chronic hepatitis C and 5% had chronic hepatitis B.1
In southeastern Michigan, 555 cases have been reported, with 457 hospitalizations (82%) and 20 deaths (4%).5 In Utah, 91 cases and 53 hospitalizations (58%) have been documented.6 In these regions, the predominant risk factors have been homelessness and illicit drug use. And many of those infected have had chronic hepatitis C (27.5%), hepatitis B (13.2%), or both (9.9%).6 In 2 of the 3 states just described, the outbreaks have involved HAV genotype 1B.1
In New York City, an outbreak starting in January 2017 resulted in 51 cases. The epidemiology of this outbreak has been different from the others, involving men who have sex with men (MSM) and the HAV genotype 1A that matches a strain circulating among MSM in Europe.7
Low adult immunity is behind the outbreaks
These outbreaks have occurred in an adult US population that has low levels of immunity to HAV. In 2012 only 12.2% of adults ages 19 to 49 years had received 2 doses of HAV vaccine8 and only 24.2% of adults had antibodies to HAV,9 showing that most adults had never been infected with the virus or vaccinated. The reduction in HAV incidence previously described is due to the introduction of targeted, and then universal, child HAV vaccination recommendations by the Advisory Committee on Immunization Practices.
As the incidence of HAV disease declined, fewer individuals became infected as children, leading later to a susceptible pool of adults who had not been infected as children and who did not receive the vaccine in adulthood. Most of these adults will not be exposed to HAV due to decreased rates of infection in children, which, historically, has been the predominant means of adult exposure. The high hospitalization and death rates encountered in the recent and ongoing large outbreaks are explained by the multiple comorbidities of those infected.
Who should be vaccinated against HAV
The CDC recommends giving HAV vaccine to all children at age one year, and to the following groups:2,10,11
- residents of a community that has a high rate of hepatitis A infection
- household members or other close personal contacts (eg, regular babysitters) of adopted children newly arrived from countries with high or intermediate hepatitis A endemicity
- men who have sex with other men
- users of illicit injection and noninjection drugs
- workers in, or travelers to, countries with high rates of hepatitis A infection
- individuals with chronic liver disease
- individuals who work with HAV-infected animals or with HAV in a research setting.
Outbreak-specific vaccine recommendations
The CDC has additionally recommended that, during outbreaks, health care providers should consider taking the following 4 steps:12,13
- Increase the availability of HAV vaccine to the homeless and to those who use illicit drugs; to anyone who has ongoing, close contact with people who are homeless or who use injection and non-injection drugs; and as post-exposure prophylaxis for unvaccinated people who have been exposed to HAV in the previous 2 weeks.
- Defer the second dose of HAV vaccine if it is in short supply.
- Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
- Use TWINRIX if other HAV vaccines are unavailable, keeping in mind that a single dose of TWINRIX achieves 94% protection against HAV but only 31% against hepatitis B virus (HBV). Three doses of TWINRIX are needed for full protection against HBV.
Available vaccines
Three vaccines are available for protection against HAV (TABLE2,14). Post-exposure prevention of HAV can be achieved with HAV vaccine or immune globulin.15 Vaccine is preferred for individuals up to age 40 years and can be used for older individuals if immune globulin is unavailable.
The CDC reports that the supply of adult HAV vaccine is being strained by these large outbreaks.16 Physicians will need to stay in touch with their local public health departments regarding vaccine availability in the community and any local recommendations being made regarding vaccine administration, as well as to the status of any local HAV outbreaks.
The epidemiology of hepatitis A virus (HAV) disease has changed. Since July 2016, there have been 5 large outbreaks of infection involving more than 1600 cases,1 with affected states requiring assistance from the Centers for Disease Control and Prevention (CDC). Two of these outbreaks were foodborne, and 3 involved person-to-person transmission.1
Before 2016, the number of outbreaks had been very low, and were predominantly associated with contaminated food, infected food handlers, and other food service-related exposures. Total annual cases of HAV infection had been declining steadily in all age groups since 1995 when HAV vaccine became available, from an estimated 271,000 cases resulting in 100 deaths2 to an estimated 2800 cases (with 1390 reported) resulting in 67 deaths in 2015 (FIGURE).3
Extent of the outbreaks
The largest hepatitis A outbreak involving person-to-person transmission in the United States in the past 20 years is occurring now in California. Predominantly affected are the homeless and users of illicit drugs, whose risk of infection is compounded by exposure to fecally-contaminated environments. As of December 1, the largest number of cases were recorded in San Diego (567), Santa Cruz (76), and Los Angeles (11).4 Adding 18 cases from other locations, the total has reached 672, resulting in 430 hospitalizations (64%) and 21 deaths (3%).4 In San Diego, 20% of those infected also had chronic hepatitis C and 5% had chronic hepatitis B.1
In southeastern Michigan, 555 cases have been reported, with 457 hospitalizations (82%) and 20 deaths (4%).5 In Utah, 91 cases and 53 hospitalizations (58%) have been documented.6 In these regions, the predominant risk factors have been homelessness and illicit drug use. And many of those infected have had chronic hepatitis C (27.5%), hepatitis B (13.2%), or both (9.9%).6 In 2 of the 3 states just described, the outbreaks have involved HAV genotype 1B.1
In New York City, an outbreak starting in January 2017 resulted in 51 cases. The epidemiology of this outbreak has been different from the others, involving men who have sex with men (MSM) and the HAV genotype 1A that matches a strain circulating among MSM in Europe.7
Low adult immunity is behind the outbreaks
These outbreaks have occurred in an adult US population that has low levels of immunity to HAV. In 2012 only 12.2% of adults ages 19 to 49 years had received 2 doses of HAV vaccine8 and only 24.2% of adults had antibodies to HAV,9 showing that most adults had never been infected with the virus or vaccinated. The reduction in HAV incidence previously described is due to the introduction of targeted, and then universal, child HAV vaccination recommendations by the Advisory Committee on Immunization Practices.
As the incidence of HAV disease declined, fewer individuals became infected as children, leading later to a susceptible pool of adults who had not been infected as children and who did not receive the vaccine in adulthood. Most of these adults will not be exposed to HAV due to decreased rates of infection in children, which, historically, has been the predominant means of adult exposure. The high hospitalization and death rates encountered in the recent and ongoing large outbreaks are explained by the multiple comorbidities of those infected.
Who should be vaccinated against HAV
The CDC recommends giving HAV vaccine to all children at age one year, and to the following groups:2,10,11
- residents of a community that has a high rate of hepatitis A infection
- household members or other close personal contacts (eg, regular babysitters) of adopted children newly arrived from countries with high or intermediate hepatitis A endemicity
- men who have sex with other men
- users of illicit injection and noninjection drugs
- workers in, or travelers to, countries with high rates of hepatitis A infection
- individuals with chronic liver disease
- individuals who work with HAV-infected animals or with HAV in a research setting.
Outbreak-specific vaccine recommendations
The CDC has additionally recommended that, during outbreaks, health care providers should consider taking the following 4 steps:12,13
- Increase the availability of HAV vaccine to the homeless and to those who use illicit drugs; to anyone who has ongoing, close contact with people who are homeless or who use injection and non-injection drugs; and as post-exposure prophylaxis for unvaccinated people who have been exposed to HAV in the previous 2 weeks.
- Defer the second dose of HAV vaccine if it is in short supply.
- Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
- Use TWINRIX if other HAV vaccines are unavailable, keeping in mind that a single dose of TWINRIX achieves 94% protection against HAV but only 31% against hepatitis B virus (HBV). Three doses of TWINRIX are needed for full protection against HBV.
Available vaccines
Three vaccines are available for protection against HAV (TABLE2,14). Post-exposure prevention of HAV can be achieved with HAV vaccine or immune globulin.15 Vaccine is preferred for individuals up to age 40 years and can be used for older individuals if immune globulin is unavailable.
The CDC reports that the supply of adult HAV vaccine is being strained by these large outbreaks.16 Physicians will need to stay in touch with their local public health departments regarding vaccine availability in the community and any local recommendations being made regarding vaccine administration, as well as to the status of any local HAV outbreaks.
1. Nelson N. Hepatitis A outbreaks. Presented at: Advisory Committee on Immunization Practices; October 25, 2017; Atlanta, GA. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-10/hepatitis-04-nelson.pdf. Accessed December 5, 2017.
2. CDC. Prevention of hepatitis A through passive or active immunization. Recommendations of the Advisory Committee on Immunization Practices. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm. Accessed November 28, 2017.
3. CDC. Viral hepatitis surveillance—United States, 2015. Available at: https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanceRpt.pdf. Accessed November 28, 2017.
4. California Department of Public Health. Hepatitis A outbreak in California. Available at: https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/Immunization/Hepatitis-A-Outbreak.aspx. Accessed November 28, 2017.
5. Michigan Department of Health & Human Services. Hepatitis A southeast Michigan outbreak. Available at: http://www.michigan.gov/mdhhs/0,5885,7-339-71550_2955_2976_82305_82310-447907--,00.html. Accessed November 28, 2017.
6. Utah Department of Health. Hepatitis A outbreak. Available at: http://health.utah.gov/epi/diseases/hepatitisA/HAVoutbreak_2017. Accessed November 28, 2017.
7. Latash J, Dorsinville M, Del Rosso P, et al. Notes from the field: increase in reported hepatitis A infections among men who have sex with men–New York City, January-August 2017. MMWR Morb Mortal Wkly Rep. 2017;66:999-1000.
8. CDC. Murphy TV, Denniston MM, Hill HA, et al. Progress toward eliminating hepatitis A disease in the United States. MMWR Morb Mortal Wkly Rep. 2016;65:29-41.
9. Klevens RM, Denniston MM, Jiles-Chapman RB, et al. Decreasing immunity to hepatitis A virus infection among US adults: findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012. Vaccine. 2015;33:6192-6198.
10. CDC. Vaccines and preventable diseases. Hepatitis A in-short. Available at: https://www.cdc.gov/vaccines/vpd/hepa/public/in-short-adult.html#who. Accessed November 20, 2017.
11. CDC. Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep. 2009;58:1006-1007.
12. CDC. Interim outbreak-specific guidance on hepatitis A vaccine administration. Available at: https://www.cdc.gov/hepatitis/outbreaks/InterimOutbreakGuidance-HAV-VaccineAdmin.htm. Accessed November 20, 2017.
13. CDC. 2017–Outbreaks of hepatitis A in multiple states among people who are homeless and people who use drugs. Available at: https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm. Accessed December 11, 2017.
14. CDC. Notice to readers: FDA approval of an alternate dosing schedule for a combined hepatitis A and B vaccine (Twinrix). Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5640a5.htm. Accessed December 8, 2017.
15. CDC. Update: prevention of hepatitis A after exposure to hepatitis A virus and in International Travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56:1080-1084.
16. CDC. Current vaccine shortages and delays. Available at: https://www.cdc.gov/vaccines/hcp/clinical-resources/shortages.html. Accessed November 28, 2017.
1. Nelson N. Hepatitis A outbreaks. Presented at: Advisory Committee on Immunization Practices; October 25, 2017; Atlanta, GA. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2017-10/hepatitis-04-nelson.pdf. Accessed December 5, 2017.
2. CDC. Prevention of hepatitis A through passive or active immunization. Recommendations of the Advisory Committee on Immunization Practices. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm. Accessed November 28, 2017.
3. CDC. Viral hepatitis surveillance—United States, 2015. Available at: https://www.cdc.gov/hepatitis/statistics/2015surveillance/pdfs/2015HepSurveillanceRpt.pdf. Accessed November 28, 2017.
4. California Department of Public Health. Hepatitis A outbreak in California. Available at: https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/Immunization/Hepatitis-A-Outbreak.aspx. Accessed November 28, 2017.
5. Michigan Department of Health & Human Services. Hepatitis A southeast Michigan outbreak. Available at: http://www.michigan.gov/mdhhs/0,5885,7-339-71550_2955_2976_82305_82310-447907--,00.html. Accessed November 28, 2017.
6. Utah Department of Health. Hepatitis A outbreak. Available at: http://health.utah.gov/epi/diseases/hepatitisA/HAVoutbreak_2017. Accessed November 28, 2017.
7. Latash J, Dorsinville M, Del Rosso P, et al. Notes from the field: increase in reported hepatitis A infections among men who have sex with men–New York City, January-August 2017. MMWR Morb Mortal Wkly Rep. 2017;66:999-1000.
8. CDC. Murphy TV, Denniston MM, Hill HA, et al. Progress toward eliminating hepatitis A disease in the United States. MMWR Morb Mortal Wkly Rep. 2016;65:29-41.
9. Klevens RM, Denniston MM, Jiles-Chapman RB, et al. Decreasing immunity to hepatitis A virus infection among US adults: findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012. Vaccine. 2015;33:6192-6198.
10. CDC. Vaccines and preventable diseases. Hepatitis A in-short. Available at: https://www.cdc.gov/vaccines/vpd/hepa/public/in-short-adult.html#who. Accessed November 20, 2017.
11. CDC. Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep. 2009;58:1006-1007.
12. CDC. Interim outbreak-specific guidance on hepatitis A vaccine administration. Available at: https://www.cdc.gov/hepatitis/outbreaks/InterimOutbreakGuidance-HAV-VaccineAdmin.htm. Accessed November 20, 2017.
13. CDC. 2017–Outbreaks of hepatitis A in multiple states among people who are homeless and people who use drugs. Available at: https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm. Accessed December 11, 2017.
14. CDC. Notice to readers: FDA approval of an alternate dosing schedule for a combined hepatitis A and B vaccine (Twinrix). Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5640a5.htm. Accessed December 8, 2017.
15. CDC. Update: prevention of hepatitis A after exposure to hepatitis A virus and in International Travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;56:1080-1084.
16. CDC. Current vaccine shortages and delays. Available at: https://www.cdc.gov/vaccines/hcp/clinical-resources/shortages.html. Accessed November 28, 2017.
The evidence for herbal and botanical remedies, Part 1
The National Center for Complementary and Integrative Health, a division of the National Institutes of Medicine, estimates that about 38% of American adults use complementary and alternative medicine.1 That statistic includes 17.7% who say they use natural products. Despite their popularity, many physicians remain skeptical—and for good reason. Enthusiasts frequently offer dramatic anecdotes to “prove” their supplements' worth, but little scientific support is available for most herbal remedies. There are, however, exceptions. As this review of the medical literature will reveal, there is evidence to support the use of capsaicin to relieve osteoarthritis (OA) and postherpetic neuralgia (PHN) and support for green tea to serve as a lipid-lowering agent and help treat diabetes. Similarly, researchers have found that peppermint may be of value in the management of irritable bowel syndrome (IBS). (We also review the literature on butterbur for migraine headaches, but serious safety issues exist; TABLE.)
In the second part of this series, which is available here, we explore what the evidence tells us about the use of turmeric, chamomile, rosemary, coffee, and cocoa.
Worth noting as you consider this—or any—review of herbals is that while there is limited scientific evidence to establish the safety and efficacy of most herbal products, they are nonetheless freely sold without US Food & Drug Administration (FDA) approval because under current regulations, they are considered dietary supplements. That legal designation means companies can manufacture, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Because herbal medications do not require the same testing through the large randomized controlled trials (RCTs) required for pharmaceuticals, evidence is often based on smaller RCTs and other studies of lower overall quality. Despite these limitations, we believe it’s worth keeping an open mind about the value of evidence-based herbal and botanical treatments.
Capsaicin
Overview
Capsaicin, an active compound in chili peppers, provokes a burning sensation, but also has a long history of use in pain treatment.2 Qutenza, an FDA-approved chemically synthesized 8% capsaicin patch, is identical to the naturally occurring molecule.2 Topically applied capsaicin exerts its therapeutic effect by rapidly depleting substance P, thus reducing the transmission of pain from C fibers to higher neurologic centers in the area of administration.3
Meta-analyses and systematic reviews have shown capsaicin is effective for various painful conditions, including peripheral diabetic neuropathy, OA, and PHN.
Peripheral neuropathy.
OA. Capsaicin provides mild to moderate efficacy in randomized trials for patients with hand and knee OA, when compared with placebo.5-7 A systematic review of capsaicin for all osteoarthritic conditions noted that there was consistent evidence that capsaicin gel was effective for OA.8 However, a 2013 Cochrane review of only knee OA noted that capsicum extract did not provide significant clinical improvement for pain or function in knee OA and resulted in a significant number of adverse events.9
Low back pain (LBP). Based on a 2014 Cochrane review of 3 trials (755 subjects) of moderate quality, capsicum frutescens cream or plaster appeared more efficacious than placebo in people with chronic LBP.10 Based on current (low-quality) evidence in one trial, however, it’s not clear whether topical capsicum cream is more beneficial for acute LBP than a placebo.10
PHN. Topical 8% capsaicin is an FDA-approved treatment for PHN. A review and cost-effectiveness analysis demonstrated that 8% capsaicin had significantly higher effectiveness rates than the oral agents (tricyclic antidepressants, duloxetine, gabapentin, pregabalin) used to treat PHN.11 In addition, the cost-effectiveness analysis found that the capsaicin patch was similar in cost to a topical lidocaine patch and oral products for PHN.11
A meta-analysis of 7 RCTs indicated that 8% topical capsaicin was superior to the low-dose capsaicin patch for relieving pain associated with PHN.12
Adverse effects
Very few toxic effects have been reported during a half century of capsaicin use. Those that have been reported are mainly limited to mild local reactions.2 The most common adverse effect of topical capsaicin is local irritation (burning, stinging, and erythema), which had been reported to occur in approximately 40% of patients.6 Nevertheless, more than 90% of the subjects in clinical studies were able to complete the studies, and pain rapidly resolved after patch removal.2 Washing with soap and water may help prevent the compound from spreading to other parts of the body unintentionally.
The safety of the patch has been demonstrated with repeated dosing every 3 months for up to one year. However, the long-term risks of chronic capsaicin use and its effect on epidermal innervation are uncertain.5
The bottom line
Capsaicin appears to be an effective treatment for neuropathy and chronic LBP. It is FDA approved for the treatment of PHN. It may also benefit patients with OA and acute LBP. Serious adverse effects are uncommon with topical use. Common adverse effects include burning pain and irritation in the area of application, which can be intense and cause discontinuation.2
Butterbur
Overview
Petasites hybridus, also known as butterbur, is a member of the daisy family, Asteraceae, and is a perennial plant found throughout Europe and Asia.13 It was used as a remedy for ulcers, wounds, and inflammation in ancient Greece. Its calcium channel-blocking effects may counteract vasoconstriction and play a role in preventing hyper-excitation of neurons.14 Sesquiterpenes, the pharmacologically active compounds in butterbur, have strong anti-inflammatory and vasodilatory effects through lipoxygenase and leukotriene inhibition.14
Migraine headache. Butterbur appears to be effective in migraine prophylaxis. Several studies have shown butterbur to significantly reduce the number of migraine attacks per month when compared with placebo. In a small, randomized, placebo-controlled, parallel-group study on the efficacy and tolerability of a special butterbur root extract (Petadolex) for the prevention of migraine, response rate was 45% in the butterbur group vs 15% in the placebo group. Butterbur was well tolerated.15 Similar results were found in another RCT in which Petasites (butterbur) 75 mg bid significantly reduced migraine attack frequency by 48%, compared with 26% for the placebo group.16 Petadolex was well tolerated in this study, too, and no serious adverse events occurred. Findings suggest that 75 mg bid may be a good option for migraine prevention given the agent's safety profile.
Petadolex may also be a good option in pediatric migraine. A 2005 study in children and adolescents found that 77% of patients experienced a reduction in attacks by at least 50% with butterbur. Patients were treated with 50 mg to 150 mg over 4 months.17
In their guidelines for migraine prevention, the American Academy of Neurology (AAN) and American Headache Society gave butterbur a Level A recommendation and concluded that butterbur should be offered to patients with migraine to reduce the frequency and severity of migraine attacks.18 However, the AAN has since changed its position, stating that “The 2012 AAN guideline, ‘Evidence-based guideline update: NSAIDS and other complementary treatments for episodic migraine prevention in adults’ has been retired by the AAN Board of Directors on September 16, 2015, due to serious safety concerns with a preventative treatment, butterbur, recommended by this guideline. The recommendations and conclusions in all retired guidelines are considered no longer valid and no longer supported by the AAN.”19
Allergic rhinitis. Although the data is not convincing, some studies have shown that butterbur may be beneficial for the treatment of allergic rhinitis.20,21
Adverse effects
While the butterbur plant itself contains pyrrolizidine alkaloids (PA), which are hepatotoxic and carcinogenic, extracts of butterbur root that are almost completely free from these alkaloids are available. (Patients who choose to use butterbur should be advised to use only products that are certified and labeled pyrrolizidine alkaloids free.)
Petadolex, the medication used in migraine studies, was initially approved by the German health regulatory authority, but approval was later withdrawn due to concerns about liver toxicity.22 In 2012, the United Kingdom’s Medicines and Health Care Products Regulatory Agency withdrew all butterbur products from the market due to associated cases of liver toxicity.22 Petasites (butterbur) products are still available in the US market, and the risks and benefits should be discussed with all patients considering this treatment. Liver function monitoring is recommended for all patients using butterbur.22
The herb can also cause dyspepsia, headache, itchy eyes, gastrointestinal symptoms, asthma, fatigue, and drowsiness. Additionally, people who are allergic to ragweed and daisies may have allergic reactions to butterbur. Eructation (belching) occurred in 7% of patients in a pediatric study.17
The bottom line
Butterbur appears to be efficacious for migraine prophylaxis, but long-term safety is unknown and serious concerns exist for liver toxicity.
Green tea
Overview
Most tea leaves come from the Camellia sinensis bush, but green and black tea are processed differently to produce different end products.23 It is estimated that green tea accounts for approximately a quarter of all tea consumption, and is most commonly consumed in Asian countries.23 The health-promoting effects of green tea are mainly attributed to its polyphenol content.24 While there are many types of tea due to how they are processed, green tea has the highest concentration of polyphenols, including catechins, which are powerful antioxidants.23,24 Green tea has been used in traditional Chinese and Indian medicine to control bleeding, improve digestion, and promote overall health.23
Dementia. Green tea polyphenols may enhance cognition and may protect against the development of dementia. In-vitro studies have shown that green tea reduces hydrogen peroxide and beta-amyloid peptides, which are significant in the development of Alzheimer’s disease.25 A 12-subject double-blind study found green tea increased working memory and had an impact on frontoparietal brain connections.26 Furthermore, a cohort study with 13,645 Japanese participants over a 5-year period found that frequent green tea consumption (>5 cups per day) was associated with a lower risk of dementa.27 Additional studies are needed, but green tea may be useful in the treatment or prevention of dementia in the future.
Coronary artery disease. In one study, green tea plasma and urinary concentrations were associated with plasma biomarkers of cardiovascular disease and diabetes.28 In one review, the consumption of green tea was associated with a statistically significant reduction in low-density lipoprotein cholesterol.29 Furthermore, a 2015 systematic review and meta-analysis of prospective observational studies concluded that increased tea consumption (of any type) is associated with a reduced risk of coronary heart disease, cardiac death, stroke, and total mortality.30
Cancer. Many studies have shown that green tea may reduce the risk of cancer development, although epidemiologic evidence is inconsistent. Studies have shown that cancer rates tend to be lower in those who consume higher levels of green tea.31,32 Whether this can be attributed solely to green tea remains debatable. Several other studies have shown that polyphenols in green tea can inhibit the growth of cancer cells, but the exact mechanisms by which tea interacts with cancerous cells is unknown.23
Several population-based studies have been performed, mostly in Japan, which showed green tea consumption reduced the risk of developing cancer. Fewer prostate cancer cases have been reported in men who consume green tea.33 While studies have been performed to determine whether green tea has effects on pancreatic, esophageal, ovarian, breast, bladder, and colorectal cancer, the evidence remains inadequate.32
Diabetes. Green tea has been shown in several studies to have a beneficial effect on diabetes. A retrospective Japanese cohort study showed that those who consumed green tea were one-third less likely to develop type 2 diabetes mellitus.34 A 10-year study from Taiwan found lower body fat and smaller waist circumference in those who consumed green tea regularly.35 A 2014 meta-analysis and systematic review of tea (any type) consumption and the risk of diabetes concluded that 3 cups or more of tea per day was associated with a lower risk of diabetes.36 Another meta-analysis that included 17 RCTs and that focused on green tea concluded that green tea improves glucose control and A1C values.37
Adverse effects
There have been concerns about potential hepatotoxicity induced by green tea intake.38 However, a systematic review of 34 RCTs on liver-related adverse events from green tea showed only a slight elevation in liver function tests; no serious liver-related adverse events were reported.38 This review suggested that liver-related adverse events after intake of green tea extracts are rare.38
Consuming green tea in the diet may lower the risk of adverse effects since the concentration consumed is generally much lower than that found in extracts.
Contraindications to drinking green tea are few. Individuals with caffeine sensitivities could experience insomnia, anxiety, irritability, or upset stomach. Additionally, patients who are taking anticoagulation drugs, such as warfarin, should avoid green tea due to its vitamin K content, which can counter the effects of warfarin. Pregnant or breastfeeding women, those with heart problems or high blood pressure, kidney or liver problems, stomach ulcers, or anxiety disorders should use caution with green tea consumption.
The bottom line
Green tea consumption in the diet appears to be safe and may have beneficial effects on weight, diabetes mellitus risk, cancer risk, dementia, and cardiovascular risk. Patients may want to consider drinking green tea as part of a healthy diet, in combination with exercise.
Mint/peppermint/menthol
Overview
Mentha piperita, also known as peppermint, is a hybrid between water mint and spearmint. It is found throughout Europe and North America and is commonly used in tea and toothpaste and as a flavoring for gum. It is used both orally and topically. Menthol and methyl salicylate are the main active ingredients in peppermint, and peppermint has calcium channel-blocker effects.39 Menthol has been shown to help regulate cold and pain sensation through the TRPM8 receptor.40 The peppermint herb has been studied in the treatment of multiple conditions.
IBS. It appears that peppermint inhibits spontaneous peristaltic activity, which reduces gastric emptying, decreases basal tone in the gastrointestinal tract, and slows down peristalsis in the gut.39
The American College of Gastroenterology guidelines currently note that there is moderate-quality evidence for peppermint oil in the treatment of IBS.41 A Cochrane review concluded that peppermint appears to be beneficial for IBS-related symptoms and pain.42 In a systematic review of 9 studies from 2014, peppermint oil was found to be more effective than placebo for IBS symptoms such as pain, bloating, gas, and diarrhea.43 The review also indicated that peppermint oil is safe, with heartburn being the most common complaint.43 A 2016 study also found that triple-coated microspheres containing peppermint oil reduced the frequency and intensity of IBS symptoms.44
Non-ulcer dyspepsia. In combination with caraway oil, peppermint oil can be used to reduce symptoms of non-ulcer dyspepsia.45,46 A multicenter, randomized, placebo-controlled, double-blind study found that 43.3% of subjects improved with a peppermint-caraway oil combination after 8 weeks, compared with 3.5% receiving placebo.46
Barium enema-related colonic spasm. Peppermint can relax the lower esophageal sphincter, and it has been shown to be useful as an antispasmodic agent for barium enema-related colonic spasm.47,48
Itching/skin irritation. Peppermint, when applied topically, has been used to calm pruritus and relieve irritation and inflammation. It has a soothing and cooling effect on the skin. At least one study found it to be effective in the treatment of pruritus gravidarum, although the study population consisted of only 96 subjects.49
Migraine headache. Initial small trials suggest that menthol is likely beneficial for migraine headaches. A pilot trial of 25 patients treated with topical menthol 6% gel for an acute migraine attack showed a significant improvement in headache intensity by 2 hours after gel application.50 In a randomized, triple-blind, placebo-controlled, crossover study of 35 patients, a menthol 10% solution was shown to be more efficacious as abortive treatment of migraine headaches than placebo.51
Tension headache. A randomized, placebo-controlled double-blind crossover study of topical peppermint oil showed a significant clinical reduction in tension headache pain.52 Another small randomized, double-blind trial showed that tiger balm (containing menthol as the main ingredient) also produced statistically significant improvement in tension headache discomfort compared with placebo.53
Musculoskeletal pain. A small study comparing topical menthol to ice for muscle soreness noted decreased perceived discomfort with menthol.54 Menthol has also been shown to reduce pain in patients with knee OA.55
Carpal tunnel syndrome (CTS). A triple-blind, randomized, placebo-controlled trial concluded that topical menthol acutely reduced pain intensity during the working day in slaughterhouse workers with CTS and should be considered as an effective non-systemic alternative to regular analgesics in the workplace management of chronic and neuropathic pain.56
Adverse effects
Peppermint appears to be safe for most adults when used in small doses, and serious adverse effects are rare.43,57 While peppermint tea appears to be safe in moderate to large amounts, people allergic to plants in the peppermint family (eg, mint, thyme, sage, rosemary, marjoram, basil, lavender) may experience allergic reactions with swelling, wheals, or erythema. Peppermint may also cause heartburn due to relaxation of the cardiac sphincter.
Other symptoms may include nausea, vomiting, flushing, and headache.58 The herb may also be both hepatotoxic and nephrotoxic at extremely high doses.59 Other considerations for women are that it can trigger menstruation and should be avoided during pregnancy. Due to uncertain efficacy in this population, peppermint oil should not be used on the face of infants, young children, or pregnant women.58,59
The bottom line
Peppermint appears to be safe and well-tolerated. It is useful in alleviating IBS symptoms and may be effective in the treatment of non-ulcerative dyspepsia, musculoskeletal pain, headache, and carpal tunnel syndrome.54,55
Read part 2 here.
CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].
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2. Wallace M, Pappagallo M. Qutenza: a capsaicin 8% patch for the management of postherpetic neuralgia. Expert Rev Neurother. 2011;11:15-27.
3. Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging. 1995;7:317-328.
4. Derry S, Sven-Rice A, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;(2):CD007393.
5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328:991.
6. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther. 1991;13:383.
7. McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol. 1992;19:604.
8. De Silva V, El-Metwally A, Ernst E, et al; Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011;50:911-920.
9. Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.
10. Oltean H, Robbins C, van Tulder MW, et al. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014;(12):CD004504.
11. Armstrong EP, Malone DC, McCarberg B, et al. Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia. Curr Med Res Opin. 2011;27:939-950.
12. Mou J, Paillard F, Turnbull B, et al. Efficacy of Qutenza (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154:1632-1639.
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15. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51:89-97.
16. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
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18. Holland S, Silberstein SD, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1346-1353.
19. American Academy of Neurology. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: [RETIRED]. Sept 16, 2015. Available at: http://n.neurology.org/content/78/17/1346. Accessed December 14, 2017.
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21. Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: a systematic review. Ann Allergy Asthma Immunol. 2007;99:483-495.
22. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
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25. Okello EJ, McDougall GJ, Kumar S, et al. In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aβ((1-42))) induced cytotoxicity in differentiated PC12 cells. Phytomedicine. 2011;15;18:691-696.
26. Schmidt A, Hammann F, Wölnerhanssen B, et al. Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology (Berl). 2014;231:3879-3888.
27. Tomata Y, Sugiyama K, Kaiho Y, et al. Green tea consumption and the risk of incident dementia in elderly japanese: The Ohsaki Cohort 2006 Study. Am J Geriatr Psychiatry. 2016;24:881-889.
28. Takechi R, Alfonso H, Hiramatsu N, et al. Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women. Nutr Res. 2016;36:220-226.
29. Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111:1720-1729.
30. Zhang C, Qin YY, Wei X, et al. Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies. Eur J Epidemiol. 2015;30:103-113.
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33. Kurahashi N, Sasazuki S, Iwasaki M, et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008;167:71-77.
34. Iso H, Date C, Wakai K, et al. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med. 2006;144:554-562.
35. Kim HM, Kim J. The effects of green tea on obesity and type 2 diabetes. Diab Metabol J. 2013;37:173-175.
36. Yang J, Mao Q, Xu H, et al. Tea consumption and risk of type 2 diabetes mellitus: a systematic review and meta-analysis update. BMJ Open. 2014;4:e005632.
37. Liu K, Zhou R, Wang B, et al. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013;98:340-348.
38. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016;70:1340.
39. Tillisch K. Complementary and alternative medicine for gastrointestinal disorders. Clin Med (Lond). 2007;7:224-227.
40. Knowlton WM, McKemy DD. TRPM8: from cold to cancer, peppermint to pain. Curr Pharm Biotechnol. 2011;12:68-77.
41. Ford AC, Moayyedi P, Lacy BE, et al. Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2-S26;quiz S27.
42. Ruepert L, Quartero AO, de Wit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.
43. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48:505-512.
44. Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Digest Dis Sci. 2016;61:560-571.
45. Holtmann G, Haag S, Adam B, et al. Effects of a fixed combination of peppermint oil and caraway oil on symptoms and quality of life in patients suffering from functional dyspepsia. Phytomedicine. 2003;10(suppl 4):56-57.
46. Madisch A, Heydenreich CJ, Wieland V, et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study. Arzneimittelforschung. 1999;49:925-932.
47. Asao T, Kuwano H, Ide M, et al. Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan. Clin Radiol. 2003;58:301-305.
48. Sparks MJ, O’Sullivan P, Herrington AA, et al. Does peppermint oil relieve spasm during barium enema? Br J Radiol. 1995;68:841-843.
49. Akhavan Amjadi M, Mojab F, Kamranpour SB. The effect of peppermint oil on symptomatic treatment of pruritus in pregnant women. Iranian J Pharm Res. 2012;11:1073-1077.
50. St Cyr A, Chen A, Bradley KC, et al. Efficacy and tolerability of STOPAIN for a migraine attack. Front Neurol. 2015;6:11.
51. Borhani Haghighi A, Motazedian S, Rezaii R, et al. Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study. Int J Clin Pract. 2010;64:451-456.
52. Gobel H, Fresenius J, Heinze A, et al. Effectiveness of oleum menthae piperitae and paracetamol in therapy of headache of the tension type [German]. Nervenarzt. 1996;67:672-681.
53. Schattner P, Randerson D. Tiger Balm as a treatment of tension headache. A clinical trial in general practice. Aust Fam Physician. 1996;25:216-220.
54. Johar P, Grover V, Topp R, et al. A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness. Int J Sports Phys Ther. 2012;7:314-322.
55. Topp R, Brosky JA Jr, Pieschel D. The effect of either topical menthol or a placebo on functioning and knee pain among patients with knee OA. J Geriatr Phys Ther. 2013;36:92-99.
56. Sundstrup E, Jakobsen MD, Brandt M, et al. Acute effect of topical menthol on chronic pain in slaughterhouse workers with carpal tunnel syndrome: triple-blind, randomized placebo-controlled trial. Rehabil Res Pract. 2014;2014:310913.
57. Nair B. Final report on the safety assessment of mentha piperita (peppermint) oil, mentha piperita (peppermint) leaf extract, mentha piperita (peppermint) leaf, and mentha piperita (peppermint) leaf water. Int J Toxicol. 2001;20(Suppl 3):61-73.
58. Klingler B, Chadhary S. Peppermint oil. Am Fam Physician. 2007;75:1027-1030.
59. Nath SS, Pandey C, Roy D. A near fatal case of high dose peppermint oil ingestion—lessons learnt. Indian J Anaesth. 2012; 56:582-
The National Center for Complementary and Integrative Health, a division of the National Institutes of Medicine, estimates that about 38% of American adults use complementary and alternative medicine.1 That statistic includes 17.7% who say they use natural products. Despite their popularity, many physicians remain skeptical—and for good reason. Enthusiasts frequently offer dramatic anecdotes to “prove” their supplements' worth, but little scientific support is available for most herbal remedies. There are, however, exceptions. As this review of the medical literature will reveal, there is evidence to support the use of capsaicin to relieve osteoarthritis (OA) and postherpetic neuralgia (PHN) and support for green tea to serve as a lipid-lowering agent and help treat diabetes. Similarly, researchers have found that peppermint may be of value in the management of irritable bowel syndrome (IBS). (We also review the literature on butterbur for migraine headaches, but serious safety issues exist; TABLE.)
In the second part of this series, which is available here, we explore what the evidence tells us about the use of turmeric, chamomile, rosemary, coffee, and cocoa.
Worth noting as you consider this—or any—review of herbals is that while there is limited scientific evidence to establish the safety and efficacy of most herbal products, they are nonetheless freely sold without US Food & Drug Administration (FDA) approval because under current regulations, they are considered dietary supplements. That legal designation means companies can manufacture, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Because herbal medications do not require the same testing through the large randomized controlled trials (RCTs) required for pharmaceuticals, evidence is often based on smaller RCTs and other studies of lower overall quality. Despite these limitations, we believe it’s worth keeping an open mind about the value of evidence-based herbal and botanical treatments.
Capsaicin
Overview
Capsaicin, an active compound in chili peppers, provokes a burning sensation, but also has a long history of use in pain treatment.2 Qutenza, an FDA-approved chemically synthesized 8% capsaicin patch, is identical to the naturally occurring molecule.2 Topically applied capsaicin exerts its therapeutic effect by rapidly depleting substance P, thus reducing the transmission of pain from C fibers to higher neurologic centers in the area of administration.3
Meta-analyses and systematic reviews have shown capsaicin is effective for various painful conditions, including peripheral diabetic neuropathy, OA, and PHN.
Peripheral neuropathy.
OA. Capsaicin provides mild to moderate efficacy in randomized trials for patients with hand and knee OA, when compared with placebo.5-7 A systematic review of capsaicin for all osteoarthritic conditions noted that there was consistent evidence that capsaicin gel was effective for OA.8 However, a 2013 Cochrane review of only knee OA noted that capsicum extract did not provide significant clinical improvement for pain or function in knee OA and resulted in a significant number of adverse events.9
Low back pain (LBP). Based on a 2014 Cochrane review of 3 trials (755 subjects) of moderate quality, capsicum frutescens cream or plaster appeared more efficacious than placebo in people with chronic LBP.10 Based on current (low-quality) evidence in one trial, however, it’s not clear whether topical capsicum cream is more beneficial for acute LBP than a placebo.10
PHN. Topical 8% capsaicin is an FDA-approved treatment for PHN. A review and cost-effectiveness analysis demonstrated that 8% capsaicin had significantly higher effectiveness rates than the oral agents (tricyclic antidepressants, duloxetine, gabapentin, pregabalin) used to treat PHN.11 In addition, the cost-effectiveness analysis found that the capsaicin patch was similar in cost to a topical lidocaine patch and oral products for PHN.11
A meta-analysis of 7 RCTs indicated that 8% topical capsaicin was superior to the low-dose capsaicin patch for relieving pain associated with PHN.12
Adverse effects
Very few toxic effects have been reported during a half century of capsaicin use. Those that have been reported are mainly limited to mild local reactions.2 The most common adverse effect of topical capsaicin is local irritation (burning, stinging, and erythema), which had been reported to occur in approximately 40% of patients.6 Nevertheless, more than 90% of the subjects in clinical studies were able to complete the studies, and pain rapidly resolved after patch removal.2 Washing with soap and water may help prevent the compound from spreading to other parts of the body unintentionally.
The safety of the patch has been demonstrated with repeated dosing every 3 months for up to one year. However, the long-term risks of chronic capsaicin use and its effect on epidermal innervation are uncertain.5
The bottom line
Capsaicin appears to be an effective treatment for neuropathy and chronic LBP. It is FDA approved for the treatment of PHN. It may also benefit patients with OA and acute LBP. Serious adverse effects are uncommon with topical use. Common adverse effects include burning pain and irritation in the area of application, which can be intense and cause discontinuation.2
Butterbur
Overview
Petasites hybridus, also known as butterbur, is a member of the daisy family, Asteraceae, and is a perennial plant found throughout Europe and Asia.13 It was used as a remedy for ulcers, wounds, and inflammation in ancient Greece. Its calcium channel-blocking effects may counteract vasoconstriction and play a role in preventing hyper-excitation of neurons.14 Sesquiterpenes, the pharmacologically active compounds in butterbur, have strong anti-inflammatory and vasodilatory effects through lipoxygenase and leukotriene inhibition.14
Migraine headache. Butterbur appears to be effective in migraine prophylaxis. Several studies have shown butterbur to significantly reduce the number of migraine attacks per month when compared with placebo. In a small, randomized, placebo-controlled, parallel-group study on the efficacy and tolerability of a special butterbur root extract (Petadolex) for the prevention of migraine, response rate was 45% in the butterbur group vs 15% in the placebo group. Butterbur was well tolerated.15 Similar results were found in another RCT in which Petasites (butterbur) 75 mg bid significantly reduced migraine attack frequency by 48%, compared with 26% for the placebo group.16 Petadolex was well tolerated in this study, too, and no serious adverse events occurred. Findings suggest that 75 mg bid may be a good option for migraine prevention given the agent's safety profile.
Petadolex may also be a good option in pediatric migraine. A 2005 study in children and adolescents found that 77% of patients experienced a reduction in attacks by at least 50% with butterbur. Patients were treated with 50 mg to 150 mg over 4 months.17
In their guidelines for migraine prevention, the American Academy of Neurology (AAN) and American Headache Society gave butterbur a Level A recommendation and concluded that butterbur should be offered to patients with migraine to reduce the frequency and severity of migraine attacks.18 However, the AAN has since changed its position, stating that “The 2012 AAN guideline, ‘Evidence-based guideline update: NSAIDS and other complementary treatments for episodic migraine prevention in adults’ has been retired by the AAN Board of Directors on September 16, 2015, due to serious safety concerns with a preventative treatment, butterbur, recommended by this guideline. The recommendations and conclusions in all retired guidelines are considered no longer valid and no longer supported by the AAN.”19
Allergic rhinitis. Although the data is not convincing, some studies have shown that butterbur may be beneficial for the treatment of allergic rhinitis.20,21
Adverse effects
While the butterbur plant itself contains pyrrolizidine alkaloids (PA), which are hepatotoxic and carcinogenic, extracts of butterbur root that are almost completely free from these alkaloids are available. (Patients who choose to use butterbur should be advised to use only products that are certified and labeled pyrrolizidine alkaloids free.)
Petadolex, the medication used in migraine studies, was initially approved by the German health regulatory authority, but approval was later withdrawn due to concerns about liver toxicity.22 In 2012, the United Kingdom’s Medicines and Health Care Products Regulatory Agency withdrew all butterbur products from the market due to associated cases of liver toxicity.22 Petasites (butterbur) products are still available in the US market, and the risks and benefits should be discussed with all patients considering this treatment. Liver function monitoring is recommended for all patients using butterbur.22
The herb can also cause dyspepsia, headache, itchy eyes, gastrointestinal symptoms, asthma, fatigue, and drowsiness. Additionally, people who are allergic to ragweed and daisies may have allergic reactions to butterbur. Eructation (belching) occurred in 7% of patients in a pediatric study.17
The bottom line
Butterbur appears to be efficacious for migraine prophylaxis, but long-term safety is unknown and serious concerns exist for liver toxicity.
Green tea
Overview
Most tea leaves come from the Camellia sinensis bush, but green and black tea are processed differently to produce different end products.23 It is estimated that green tea accounts for approximately a quarter of all tea consumption, and is most commonly consumed in Asian countries.23 The health-promoting effects of green tea are mainly attributed to its polyphenol content.24 While there are many types of tea due to how they are processed, green tea has the highest concentration of polyphenols, including catechins, which are powerful antioxidants.23,24 Green tea has been used in traditional Chinese and Indian medicine to control bleeding, improve digestion, and promote overall health.23
Dementia. Green tea polyphenols may enhance cognition and may protect against the development of dementia. In-vitro studies have shown that green tea reduces hydrogen peroxide and beta-amyloid peptides, which are significant in the development of Alzheimer’s disease.25 A 12-subject double-blind study found green tea increased working memory and had an impact on frontoparietal brain connections.26 Furthermore, a cohort study with 13,645 Japanese participants over a 5-year period found that frequent green tea consumption (>5 cups per day) was associated with a lower risk of dementa.27 Additional studies are needed, but green tea may be useful in the treatment or prevention of dementia in the future.
Coronary artery disease. In one study, green tea plasma and urinary concentrations were associated with plasma biomarkers of cardiovascular disease and diabetes.28 In one review, the consumption of green tea was associated with a statistically significant reduction in low-density lipoprotein cholesterol.29 Furthermore, a 2015 systematic review and meta-analysis of prospective observational studies concluded that increased tea consumption (of any type) is associated with a reduced risk of coronary heart disease, cardiac death, stroke, and total mortality.30
Cancer. Many studies have shown that green tea may reduce the risk of cancer development, although epidemiologic evidence is inconsistent. Studies have shown that cancer rates tend to be lower in those who consume higher levels of green tea.31,32 Whether this can be attributed solely to green tea remains debatable. Several other studies have shown that polyphenols in green tea can inhibit the growth of cancer cells, but the exact mechanisms by which tea interacts with cancerous cells is unknown.23
Several population-based studies have been performed, mostly in Japan, which showed green tea consumption reduced the risk of developing cancer. Fewer prostate cancer cases have been reported in men who consume green tea.33 While studies have been performed to determine whether green tea has effects on pancreatic, esophageal, ovarian, breast, bladder, and colorectal cancer, the evidence remains inadequate.32
Diabetes. Green tea has been shown in several studies to have a beneficial effect on diabetes. A retrospective Japanese cohort study showed that those who consumed green tea were one-third less likely to develop type 2 diabetes mellitus.34 A 10-year study from Taiwan found lower body fat and smaller waist circumference in those who consumed green tea regularly.35 A 2014 meta-analysis and systematic review of tea (any type) consumption and the risk of diabetes concluded that 3 cups or more of tea per day was associated with a lower risk of diabetes.36 Another meta-analysis that included 17 RCTs and that focused on green tea concluded that green tea improves glucose control and A1C values.37
Adverse effects
There have been concerns about potential hepatotoxicity induced by green tea intake.38 However, a systematic review of 34 RCTs on liver-related adverse events from green tea showed only a slight elevation in liver function tests; no serious liver-related adverse events were reported.38 This review suggested that liver-related adverse events after intake of green tea extracts are rare.38
Consuming green tea in the diet may lower the risk of adverse effects since the concentration consumed is generally much lower than that found in extracts.
Contraindications to drinking green tea are few. Individuals with caffeine sensitivities could experience insomnia, anxiety, irritability, or upset stomach. Additionally, patients who are taking anticoagulation drugs, such as warfarin, should avoid green tea due to its vitamin K content, which can counter the effects of warfarin. Pregnant or breastfeeding women, those with heart problems or high blood pressure, kidney or liver problems, stomach ulcers, or anxiety disorders should use caution with green tea consumption.
The bottom line
Green tea consumption in the diet appears to be safe and may have beneficial effects on weight, diabetes mellitus risk, cancer risk, dementia, and cardiovascular risk. Patients may want to consider drinking green tea as part of a healthy diet, in combination with exercise.
Mint/peppermint/menthol
Overview
Mentha piperita, also known as peppermint, is a hybrid between water mint and spearmint. It is found throughout Europe and North America and is commonly used in tea and toothpaste and as a flavoring for gum. It is used both orally and topically. Menthol and methyl salicylate are the main active ingredients in peppermint, and peppermint has calcium channel-blocker effects.39 Menthol has been shown to help regulate cold and pain sensation through the TRPM8 receptor.40 The peppermint herb has been studied in the treatment of multiple conditions.
IBS. It appears that peppermint inhibits spontaneous peristaltic activity, which reduces gastric emptying, decreases basal tone in the gastrointestinal tract, and slows down peristalsis in the gut.39
The American College of Gastroenterology guidelines currently note that there is moderate-quality evidence for peppermint oil in the treatment of IBS.41 A Cochrane review concluded that peppermint appears to be beneficial for IBS-related symptoms and pain.42 In a systematic review of 9 studies from 2014, peppermint oil was found to be more effective than placebo for IBS symptoms such as pain, bloating, gas, and diarrhea.43 The review also indicated that peppermint oil is safe, with heartburn being the most common complaint.43 A 2016 study also found that triple-coated microspheres containing peppermint oil reduced the frequency and intensity of IBS symptoms.44
Non-ulcer dyspepsia. In combination with caraway oil, peppermint oil can be used to reduce symptoms of non-ulcer dyspepsia.45,46 A multicenter, randomized, placebo-controlled, double-blind study found that 43.3% of subjects improved with a peppermint-caraway oil combination after 8 weeks, compared with 3.5% receiving placebo.46
Barium enema-related colonic spasm. Peppermint can relax the lower esophageal sphincter, and it has been shown to be useful as an antispasmodic agent for barium enema-related colonic spasm.47,48
Itching/skin irritation. Peppermint, when applied topically, has been used to calm pruritus and relieve irritation and inflammation. It has a soothing and cooling effect on the skin. At least one study found it to be effective in the treatment of pruritus gravidarum, although the study population consisted of only 96 subjects.49
Migraine headache. Initial small trials suggest that menthol is likely beneficial for migraine headaches. A pilot trial of 25 patients treated with topical menthol 6% gel for an acute migraine attack showed a significant improvement in headache intensity by 2 hours after gel application.50 In a randomized, triple-blind, placebo-controlled, crossover study of 35 patients, a menthol 10% solution was shown to be more efficacious as abortive treatment of migraine headaches than placebo.51
Tension headache. A randomized, placebo-controlled double-blind crossover study of topical peppermint oil showed a significant clinical reduction in tension headache pain.52 Another small randomized, double-blind trial showed that tiger balm (containing menthol as the main ingredient) also produced statistically significant improvement in tension headache discomfort compared with placebo.53
Musculoskeletal pain. A small study comparing topical menthol to ice for muscle soreness noted decreased perceived discomfort with menthol.54 Menthol has also been shown to reduce pain in patients with knee OA.55
Carpal tunnel syndrome (CTS). A triple-blind, randomized, placebo-controlled trial concluded that topical menthol acutely reduced pain intensity during the working day in slaughterhouse workers with CTS and should be considered as an effective non-systemic alternative to regular analgesics in the workplace management of chronic and neuropathic pain.56
Adverse effects
Peppermint appears to be safe for most adults when used in small doses, and serious adverse effects are rare.43,57 While peppermint tea appears to be safe in moderate to large amounts, people allergic to plants in the peppermint family (eg, mint, thyme, sage, rosemary, marjoram, basil, lavender) may experience allergic reactions with swelling, wheals, or erythema. Peppermint may also cause heartburn due to relaxation of the cardiac sphincter.
Other symptoms may include nausea, vomiting, flushing, and headache.58 The herb may also be both hepatotoxic and nephrotoxic at extremely high doses.59 Other considerations for women are that it can trigger menstruation and should be avoided during pregnancy. Due to uncertain efficacy in this population, peppermint oil should not be used on the face of infants, young children, or pregnant women.58,59
The bottom line
Peppermint appears to be safe and well-tolerated. It is useful in alleviating IBS symptoms and may be effective in the treatment of non-ulcerative dyspepsia, musculoskeletal pain, headache, and carpal tunnel syndrome.54,55
Read part 2 here.
CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].
The National Center for Complementary and Integrative Health, a division of the National Institutes of Medicine, estimates that about 38% of American adults use complementary and alternative medicine.1 That statistic includes 17.7% who say they use natural products. Despite their popularity, many physicians remain skeptical—and for good reason. Enthusiasts frequently offer dramatic anecdotes to “prove” their supplements' worth, but little scientific support is available for most herbal remedies. There are, however, exceptions. As this review of the medical literature will reveal, there is evidence to support the use of capsaicin to relieve osteoarthritis (OA) and postherpetic neuralgia (PHN) and support for green tea to serve as a lipid-lowering agent and help treat diabetes. Similarly, researchers have found that peppermint may be of value in the management of irritable bowel syndrome (IBS). (We also review the literature on butterbur for migraine headaches, but serious safety issues exist; TABLE.)
In the second part of this series, which is available here, we explore what the evidence tells us about the use of turmeric, chamomile, rosemary, coffee, and cocoa.
Worth noting as you consider this—or any—review of herbals is that while there is limited scientific evidence to establish the safety and efficacy of most herbal products, they are nonetheless freely sold without US Food & Drug Administration (FDA) approval because under current regulations, they are considered dietary supplements. That legal designation means companies can manufacture, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Because herbal medications do not require the same testing through the large randomized controlled trials (RCTs) required for pharmaceuticals, evidence is often based on smaller RCTs and other studies of lower overall quality. Despite these limitations, we believe it’s worth keeping an open mind about the value of evidence-based herbal and botanical treatments.
Capsaicin
Overview
Capsaicin, an active compound in chili peppers, provokes a burning sensation, but also has a long history of use in pain treatment.2 Qutenza, an FDA-approved chemically synthesized 8% capsaicin patch, is identical to the naturally occurring molecule.2 Topically applied capsaicin exerts its therapeutic effect by rapidly depleting substance P, thus reducing the transmission of pain from C fibers to higher neurologic centers in the area of administration.3
Meta-analyses and systematic reviews have shown capsaicin is effective for various painful conditions, including peripheral diabetic neuropathy, OA, and PHN.
Peripheral neuropathy.
OA. Capsaicin provides mild to moderate efficacy in randomized trials for patients with hand and knee OA, when compared with placebo.5-7 A systematic review of capsaicin for all osteoarthritic conditions noted that there was consistent evidence that capsaicin gel was effective for OA.8 However, a 2013 Cochrane review of only knee OA noted that capsicum extract did not provide significant clinical improvement for pain or function in knee OA and resulted in a significant number of adverse events.9
Low back pain (LBP). Based on a 2014 Cochrane review of 3 trials (755 subjects) of moderate quality, capsicum frutescens cream or plaster appeared more efficacious than placebo in people with chronic LBP.10 Based on current (low-quality) evidence in one trial, however, it’s not clear whether topical capsicum cream is more beneficial for acute LBP than a placebo.10
PHN. Topical 8% capsaicin is an FDA-approved treatment for PHN. A review and cost-effectiveness analysis demonstrated that 8% capsaicin had significantly higher effectiveness rates than the oral agents (tricyclic antidepressants, duloxetine, gabapentin, pregabalin) used to treat PHN.11 In addition, the cost-effectiveness analysis found that the capsaicin patch was similar in cost to a topical lidocaine patch and oral products for PHN.11
A meta-analysis of 7 RCTs indicated that 8% topical capsaicin was superior to the low-dose capsaicin patch for relieving pain associated with PHN.12
Adverse effects
Very few toxic effects have been reported during a half century of capsaicin use. Those that have been reported are mainly limited to mild local reactions.2 The most common adverse effect of topical capsaicin is local irritation (burning, stinging, and erythema), which had been reported to occur in approximately 40% of patients.6 Nevertheless, more than 90% of the subjects in clinical studies were able to complete the studies, and pain rapidly resolved after patch removal.2 Washing with soap and water may help prevent the compound from spreading to other parts of the body unintentionally.
The safety of the patch has been demonstrated with repeated dosing every 3 months for up to one year. However, the long-term risks of chronic capsaicin use and its effect on epidermal innervation are uncertain.5
The bottom line
Capsaicin appears to be an effective treatment for neuropathy and chronic LBP. It is FDA approved for the treatment of PHN. It may also benefit patients with OA and acute LBP. Serious adverse effects are uncommon with topical use. Common adverse effects include burning pain and irritation in the area of application, which can be intense and cause discontinuation.2
Butterbur
Overview
Petasites hybridus, also known as butterbur, is a member of the daisy family, Asteraceae, and is a perennial plant found throughout Europe and Asia.13 It was used as a remedy for ulcers, wounds, and inflammation in ancient Greece. Its calcium channel-blocking effects may counteract vasoconstriction and play a role in preventing hyper-excitation of neurons.14 Sesquiterpenes, the pharmacologically active compounds in butterbur, have strong anti-inflammatory and vasodilatory effects through lipoxygenase and leukotriene inhibition.14
Migraine headache. Butterbur appears to be effective in migraine prophylaxis. Several studies have shown butterbur to significantly reduce the number of migraine attacks per month when compared with placebo. In a small, randomized, placebo-controlled, parallel-group study on the efficacy and tolerability of a special butterbur root extract (Petadolex) for the prevention of migraine, response rate was 45% in the butterbur group vs 15% in the placebo group. Butterbur was well tolerated.15 Similar results were found in another RCT in which Petasites (butterbur) 75 mg bid significantly reduced migraine attack frequency by 48%, compared with 26% for the placebo group.16 Petadolex was well tolerated in this study, too, and no serious adverse events occurred. Findings suggest that 75 mg bid may be a good option for migraine prevention given the agent's safety profile.
Petadolex may also be a good option in pediatric migraine. A 2005 study in children and adolescents found that 77% of patients experienced a reduction in attacks by at least 50% with butterbur. Patients were treated with 50 mg to 150 mg over 4 months.17
In their guidelines for migraine prevention, the American Academy of Neurology (AAN) and American Headache Society gave butterbur a Level A recommendation and concluded that butterbur should be offered to patients with migraine to reduce the frequency and severity of migraine attacks.18 However, the AAN has since changed its position, stating that “The 2012 AAN guideline, ‘Evidence-based guideline update: NSAIDS and other complementary treatments for episodic migraine prevention in adults’ has been retired by the AAN Board of Directors on September 16, 2015, due to serious safety concerns with a preventative treatment, butterbur, recommended by this guideline. The recommendations and conclusions in all retired guidelines are considered no longer valid and no longer supported by the AAN.”19
Allergic rhinitis. Although the data is not convincing, some studies have shown that butterbur may be beneficial for the treatment of allergic rhinitis.20,21
Adverse effects
While the butterbur plant itself contains pyrrolizidine alkaloids (PA), which are hepatotoxic and carcinogenic, extracts of butterbur root that are almost completely free from these alkaloids are available. (Patients who choose to use butterbur should be advised to use only products that are certified and labeled pyrrolizidine alkaloids free.)
Petadolex, the medication used in migraine studies, was initially approved by the German health regulatory authority, but approval was later withdrawn due to concerns about liver toxicity.22 In 2012, the United Kingdom’s Medicines and Health Care Products Regulatory Agency withdrew all butterbur products from the market due to associated cases of liver toxicity.22 Petasites (butterbur) products are still available in the US market, and the risks and benefits should be discussed with all patients considering this treatment. Liver function monitoring is recommended for all patients using butterbur.22
The herb can also cause dyspepsia, headache, itchy eyes, gastrointestinal symptoms, asthma, fatigue, and drowsiness. Additionally, people who are allergic to ragweed and daisies may have allergic reactions to butterbur. Eructation (belching) occurred in 7% of patients in a pediatric study.17
The bottom line
Butterbur appears to be efficacious for migraine prophylaxis, but long-term safety is unknown and serious concerns exist for liver toxicity.
Green tea
Overview
Most tea leaves come from the Camellia sinensis bush, but green and black tea are processed differently to produce different end products.23 It is estimated that green tea accounts for approximately a quarter of all tea consumption, and is most commonly consumed in Asian countries.23 The health-promoting effects of green tea are mainly attributed to its polyphenol content.24 While there are many types of tea due to how they are processed, green tea has the highest concentration of polyphenols, including catechins, which are powerful antioxidants.23,24 Green tea has been used in traditional Chinese and Indian medicine to control bleeding, improve digestion, and promote overall health.23
Dementia. Green tea polyphenols may enhance cognition and may protect against the development of dementia. In-vitro studies have shown that green tea reduces hydrogen peroxide and beta-amyloid peptides, which are significant in the development of Alzheimer’s disease.25 A 12-subject double-blind study found green tea increased working memory and had an impact on frontoparietal brain connections.26 Furthermore, a cohort study with 13,645 Japanese participants over a 5-year period found that frequent green tea consumption (>5 cups per day) was associated with a lower risk of dementa.27 Additional studies are needed, but green tea may be useful in the treatment or prevention of dementia in the future.
Coronary artery disease. In one study, green tea plasma and urinary concentrations were associated with plasma biomarkers of cardiovascular disease and diabetes.28 In one review, the consumption of green tea was associated with a statistically significant reduction in low-density lipoprotein cholesterol.29 Furthermore, a 2015 systematic review and meta-analysis of prospective observational studies concluded that increased tea consumption (of any type) is associated with a reduced risk of coronary heart disease, cardiac death, stroke, and total mortality.30
Cancer. Many studies have shown that green tea may reduce the risk of cancer development, although epidemiologic evidence is inconsistent. Studies have shown that cancer rates tend to be lower in those who consume higher levels of green tea.31,32 Whether this can be attributed solely to green tea remains debatable. Several other studies have shown that polyphenols in green tea can inhibit the growth of cancer cells, but the exact mechanisms by which tea interacts with cancerous cells is unknown.23
Several population-based studies have been performed, mostly in Japan, which showed green tea consumption reduced the risk of developing cancer. Fewer prostate cancer cases have been reported in men who consume green tea.33 While studies have been performed to determine whether green tea has effects on pancreatic, esophageal, ovarian, breast, bladder, and colorectal cancer, the evidence remains inadequate.32
Diabetes. Green tea has been shown in several studies to have a beneficial effect on diabetes. A retrospective Japanese cohort study showed that those who consumed green tea were one-third less likely to develop type 2 diabetes mellitus.34 A 10-year study from Taiwan found lower body fat and smaller waist circumference in those who consumed green tea regularly.35 A 2014 meta-analysis and systematic review of tea (any type) consumption and the risk of diabetes concluded that 3 cups or more of tea per day was associated with a lower risk of diabetes.36 Another meta-analysis that included 17 RCTs and that focused on green tea concluded that green tea improves glucose control and A1C values.37
Adverse effects
There have been concerns about potential hepatotoxicity induced by green tea intake.38 However, a systematic review of 34 RCTs on liver-related adverse events from green tea showed only a slight elevation in liver function tests; no serious liver-related adverse events were reported.38 This review suggested that liver-related adverse events after intake of green tea extracts are rare.38
Consuming green tea in the diet may lower the risk of adverse effects since the concentration consumed is generally much lower than that found in extracts.
Contraindications to drinking green tea are few. Individuals with caffeine sensitivities could experience insomnia, anxiety, irritability, or upset stomach. Additionally, patients who are taking anticoagulation drugs, such as warfarin, should avoid green tea due to its vitamin K content, which can counter the effects of warfarin. Pregnant or breastfeeding women, those with heart problems or high blood pressure, kidney or liver problems, stomach ulcers, or anxiety disorders should use caution with green tea consumption.
The bottom line
Green tea consumption in the diet appears to be safe and may have beneficial effects on weight, diabetes mellitus risk, cancer risk, dementia, and cardiovascular risk. Patients may want to consider drinking green tea as part of a healthy diet, in combination with exercise.
Mint/peppermint/menthol
Overview
Mentha piperita, also known as peppermint, is a hybrid between water mint and spearmint. It is found throughout Europe and North America and is commonly used in tea and toothpaste and as a flavoring for gum. It is used both orally and topically. Menthol and methyl salicylate are the main active ingredients in peppermint, and peppermint has calcium channel-blocker effects.39 Menthol has been shown to help regulate cold and pain sensation through the TRPM8 receptor.40 The peppermint herb has been studied in the treatment of multiple conditions.
IBS. It appears that peppermint inhibits spontaneous peristaltic activity, which reduces gastric emptying, decreases basal tone in the gastrointestinal tract, and slows down peristalsis in the gut.39
The American College of Gastroenterology guidelines currently note that there is moderate-quality evidence for peppermint oil in the treatment of IBS.41 A Cochrane review concluded that peppermint appears to be beneficial for IBS-related symptoms and pain.42 In a systematic review of 9 studies from 2014, peppermint oil was found to be more effective than placebo for IBS symptoms such as pain, bloating, gas, and diarrhea.43 The review also indicated that peppermint oil is safe, with heartburn being the most common complaint.43 A 2016 study also found that triple-coated microspheres containing peppermint oil reduced the frequency and intensity of IBS symptoms.44
Non-ulcer dyspepsia. In combination with caraway oil, peppermint oil can be used to reduce symptoms of non-ulcer dyspepsia.45,46 A multicenter, randomized, placebo-controlled, double-blind study found that 43.3% of subjects improved with a peppermint-caraway oil combination after 8 weeks, compared with 3.5% receiving placebo.46
Barium enema-related colonic spasm. Peppermint can relax the lower esophageal sphincter, and it has been shown to be useful as an antispasmodic agent for barium enema-related colonic spasm.47,48
Itching/skin irritation. Peppermint, when applied topically, has been used to calm pruritus and relieve irritation and inflammation. It has a soothing and cooling effect on the skin. At least one study found it to be effective in the treatment of pruritus gravidarum, although the study population consisted of only 96 subjects.49
Migraine headache. Initial small trials suggest that menthol is likely beneficial for migraine headaches. A pilot trial of 25 patients treated with topical menthol 6% gel for an acute migraine attack showed a significant improvement in headache intensity by 2 hours after gel application.50 In a randomized, triple-blind, placebo-controlled, crossover study of 35 patients, a menthol 10% solution was shown to be more efficacious as abortive treatment of migraine headaches than placebo.51
Tension headache. A randomized, placebo-controlled double-blind crossover study of topical peppermint oil showed a significant clinical reduction in tension headache pain.52 Another small randomized, double-blind trial showed that tiger balm (containing menthol as the main ingredient) also produced statistically significant improvement in tension headache discomfort compared with placebo.53
Musculoskeletal pain. A small study comparing topical menthol to ice for muscle soreness noted decreased perceived discomfort with menthol.54 Menthol has also been shown to reduce pain in patients with knee OA.55
Carpal tunnel syndrome (CTS). A triple-blind, randomized, placebo-controlled trial concluded that topical menthol acutely reduced pain intensity during the working day in slaughterhouse workers with CTS and should be considered as an effective non-systemic alternative to regular analgesics in the workplace management of chronic and neuropathic pain.56
Adverse effects
Peppermint appears to be safe for most adults when used in small doses, and serious adverse effects are rare.43,57 While peppermint tea appears to be safe in moderate to large amounts, people allergic to plants in the peppermint family (eg, mint, thyme, sage, rosemary, marjoram, basil, lavender) may experience allergic reactions with swelling, wheals, or erythema. Peppermint may also cause heartburn due to relaxation of the cardiac sphincter.
Other symptoms may include nausea, vomiting, flushing, and headache.58 The herb may also be both hepatotoxic and nephrotoxic at extremely high doses.59 Other considerations for women are that it can trigger menstruation and should be avoided during pregnancy. Due to uncertain efficacy in this population, peppermint oil should not be used on the face of infants, young children, or pregnant women.58,59
The bottom line
Peppermint appears to be safe and well-tolerated. It is useful in alleviating IBS symptoms and may be effective in the treatment of non-ulcerative dyspepsia, musculoskeletal pain, headache, and carpal tunnel syndrome.54,55
Read part 2 here.
CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].
1. National Center for Complementary and Integrative Health. The Use of Complementary and Alternative Medicine in the United States. Available at: https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Accessed November 28, 2017.
2. Wallace M, Pappagallo M. Qutenza: a capsaicin 8% patch for the management of postherpetic neuralgia. Expert Rev Neurother. 2011;11:15-27.
3. Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging. 1995;7:317-328.
4. Derry S, Sven-Rice A, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;(2):CD007393.
5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328:991.
6. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther. 1991;13:383.
7. McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol. 1992;19:604.
8. De Silva V, El-Metwally A, Ernst E, et al; Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011;50:911-920.
9. Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.
10. Oltean H, Robbins C, van Tulder MW, et al. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014;(12):CD004504.
11. Armstrong EP, Malone DC, McCarberg B, et al. Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia. Curr Med Res Opin. 2011;27:939-950.
12. Mou J, Paillard F, Turnbull B, et al. Efficacy of Qutenza (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154:1632-1639.
13. Sun-Edelstein C, Mauskop A. Alternative headache treatments: nutraceuticals, behavioral and physical treatments. Headache. 2011;51:469-483.
14. D’Andrea G, Cevoli S, Cologno D. Herbal therapy in migraine. Neurol Sci. 2014;35(Suppl 1):135-140.
15. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51:89-97.
16. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
17. Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache. 2005;45:196-203.
18. Holland S, Silberstein SD, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1346-1353.
19. American Academy of Neurology. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: [RETIRED]. Sept 16, 2015. Available at: http://n.neurology.org/content/78/17/1346. Accessed December 14, 2017.
20. Man LX. Complementary and alternative medicine for allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg. 2009;17:226-231.
21. Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: a systematic review. Ann Allergy Asthma Immunol. 2007;99:483-495.
22. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
23. Chacko SM, Thambi PT, Kuttan R, et al. Beneficial effects of green tea: a literature review. Chin Med. 2010;6:13.
24. Naghma K, Hasan M. Tea polyphenols for health promotion. Life Sciences. 2007;81:519-533.
25. Okello EJ, McDougall GJ, Kumar S, et al. In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aβ((1-42))) induced cytotoxicity in differentiated PC12 cells. Phytomedicine. 2011;15;18:691-696.
26. Schmidt A, Hammann F, Wölnerhanssen B, et al. Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology (Berl). 2014;231:3879-3888.
27. Tomata Y, Sugiyama K, Kaiho Y, et al. Green tea consumption and the risk of incident dementia in elderly japanese: The Ohsaki Cohort 2006 Study. Am J Geriatr Psychiatry. 2016;24:881-889.
28. Takechi R, Alfonso H, Hiramatsu N, et al. Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women. Nutr Res. 2016;36:220-226.
29. Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111:1720-1729.
30. Zhang C, Qin YY, Wei X, et al. Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies. Eur J Epidemiol. 2015;30:103-113.
31. Imai K, Suga K, Nakachi K. Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 1997;26:769-775.
32. Yuan JM. Cancer prevention by green tea: evidence from epidemiologic studies. Am J Clin Nutr. 2013;98(6 Suppl):1676S-1681S.
33. Kurahashi N, Sasazuki S, Iwasaki M, et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008;167:71-77.
34. Iso H, Date C, Wakai K, et al. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med. 2006;144:554-562.
35. Kim HM, Kim J. The effects of green tea on obesity and type 2 diabetes. Diab Metabol J. 2013;37:173-175.
36. Yang J, Mao Q, Xu H, et al. Tea consumption and risk of type 2 diabetes mellitus: a systematic review and meta-analysis update. BMJ Open. 2014;4:e005632.
37. Liu K, Zhou R, Wang B, et al. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013;98:340-348.
38. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016;70:1340.
39. Tillisch K. Complementary and alternative medicine for gastrointestinal disorders. Clin Med (Lond). 2007;7:224-227.
40. Knowlton WM, McKemy DD. TRPM8: from cold to cancer, peppermint to pain. Curr Pharm Biotechnol. 2011;12:68-77.
41. Ford AC, Moayyedi P, Lacy BE, et al. Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2-S26;quiz S27.
42. Ruepert L, Quartero AO, de Wit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.
43. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48:505-512.
44. Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Digest Dis Sci. 2016;61:560-571.
45. Holtmann G, Haag S, Adam B, et al. Effects of a fixed combination of peppermint oil and caraway oil on symptoms and quality of life in patients suffering from functional dyspepsia. Phytomedicine. 2003;10(suppl 4):56-57.
46. Madisch A, Heydenreich CJ, Wieland V, et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study. Arzneimittelforschung. 1999;49:925-932.
47. Asao T, Kuwano H, Ide M, et al. Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan. Clin Radiol. 2003;58:301-305.
48. Sparks MJ, O’Sullivan P, Herrington AA, et al. Does peppermint oil relieve spasm during barium enema? Br J Radiol. 1995;68:841-843.
49. Akhavan Amjadi M, Mojab F, Kamranpour SB. The effect of peppermint oil on symptomatic treatment of pruritus in pregnant women. Iranian J Pharm Res. 2012;11:1073-1077.
50. St Cyr A, Chen A, Bradley KC, et al. Efficacy and tolerability of STOPAIN for a migraine attack. Front Neurol. 2015;6:11.
51. Borhani Haghighi A, Motazedian S, Rezaii R, et al. Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study. Int J Clin Pract. 2010;64:451-456.
52. Gobel H, Fresenius J, Heinze A, et al. Effectiveness of oleum menthae piperitae and paracetamol in therapy of headache of the tension type [German]. Nervenarzt. 1996;67:672-681.
53. Schattner P, Randerson D. Tiger Balm as a treatment of tension headache. A clinical trial in general practice. Aust Fam Physician. 1996;25:216-220.
54. Johar P, Grover V, Topp R, et al. A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness. Int J Sports Phys Ther. 2012;7:314-322.
55. Topp R, Brosky JA Jr, Pieschel D. The effect of either topical menthol or a placebo on functioning and knee pain among patients with knee OA. J Geriatr Phys Ther. 2013;36:92-99.
56. Sundstrup E, Jakobsen MD, Brandt M, et al. Acute effect of topical menthol on chronic pain in slaughterhouse workers with carpal tunnel syndrome: triple-blind, randomized placebo-controlled trial. Rehabil Res Pract. 2014;2014:310913.
57. Nair B. Final report on the safety assessment of mentha piperita (peppermint) oil, mentha piperita (peppermint) leaf extract, mentha piperita (peppermint) leaf, and mentha piperita (peppermint) leaf water. Int J Toxicol. 2001;20(Suppl 3):61-73.
58. Klingler B, Chadhary S. Peppermint oil. Am Fam Physician. 2007;75:1027-1030.
59. Nath SS, Pandey C, Roy D. A near fatal case of high dose peppermint oil ingestion—lessons learnt. Indian J Anaesth. 2012; 56:582-
1. National Center for Complementary and Integrative Health. The Use of Complementary and Alternative Medicine in the United States. Available at: https://nccih.nih.gov/research/statistics/2007/camsurvey_fs1.htm. Accessed November 28, 2017.
2. Wallace M, Pappagallo M. Qutenza: a capsaicin 8% patch for the management of postherpetic neuralgia. Expert Rev Neurother. 2011;11:15-27.
3. Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging. 1995;7:317-328.
4. Derry S, Sven-Rice A, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2013;(2):CD007393.
5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328:991.
6. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther. 1991;13:383.
7. McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol. 1992;19:604.
8. De Silva V, El-Metwally A, Ernst E, et al; Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of osteoarthritis: a systematic review. Rheumatology (Oxford). 2011;50:911-920.
9. Cameron M, Chrubasik S. Topical herbal therapies for treating osteoarthritis. Cochrane Database Syst Rev. 2013;(5):CD010538.
10. Oltean H, Robbins C, van Tulder MW, et al. Herbal medicine for low-back pain. Cochrane Database Syst Rev. 2014;(12):CD004504.
11. Armstrong EP, Malone DC, McCarberg B, et al. Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia. Curr Med Res Opin. 2011;27:939-950.
12. Mou J, Paillard F, Turnbull B, et al. Efficacy of Qutenza (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154:1632-1639.
13. Sun-Edelstein C, Mauskop A. Alternative headache treatments: nutraceuticals, behavioral and physical treatments. Headache. 2011;51:469-483.
14. D’Andrea G, Cevoli S, Cologno D. Herbal therapy in migraine. Neurol Sci. 2014;35(Suppl 1):135-140.
15. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol. 2004;51:89-97.
16. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.
17. Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache. 2005;45:196-203.
18. Holland S, Silberstein SD, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1346-1353.
19. American Academy of Neurology. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: [RETIRED]. Sept 16, 2015. Available at: http://n.neurology.org/content/78/17/1346. Accessed December 14, 2017.
20. Man LX. Complementary and alternative medicine for allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg. 2009;17:226-231.
21. Guo R, Pittler MH, Ernst E. Herbal medicines for the treatment of allergic rhinitis: a systematic review. Ann Allergy Asthma Immunol. 2007;99:483-495.
22. Daniel O, Mauskop A. Nutraceuticals in acute and prophylactic treatment of migraine. Curr Treat Options Neurol. 2016;18:14.
23. Chacko SM, Thambi PT, Kuttan R, et al. Beneficial effects of green tea: a literature review. Chin Med. 2010;6:13.
24. Naghma K, Hasan M. Tea polyphenols for health promotion. Life Sciences. 2007;81:519-533.
25. Okello EJ, McDougall GJ, Kumar S, et al. In vitro protective effects of colon-available extract of Camellia sinensis (tea) against hydrogen peroxide and beta-amyloid (Aβ((1-42))) induced cytotoxicity in differentiated PC12 cells. Phytomedicine. 2011;15;18:691-696.
26. Schmidt A, Hammann F, Wölnerhanssen B, et al. Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology (Berl). 2014;231:3879-3888.
27. Tomata Y, Sugiyama K, Kaiho Y, et al. Green tea consumption and the risk of incident dementia in elderly japanese: The Ohsaki Cohort 2006 Study. Am J Geriatr Psychiatry. 2016;24:881-889.
28. Takechi R, Alfonso H, Hiramatsu N, et al. Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women. Nutr Res. 2016;36:220-226.
29. Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111:1720-1729.
30. Zhang C, Qin YY, Wei X, et al. Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies. Eur J Epidemiol. 2015;30:103-113.
31. Imai K, Suga K, Nakachi K. Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 1997;26:769-775.
32. Yuan JM. Cancer prevention by green tea: evidence from epidemiologic studies. Am J Clin Nutr. 2013;98(6 Suppl):1676S-1681S.
33. Kurahashi N, Sasazuki S, Iwasaki M, et al. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. 2008;167:71-77.
34. Iso H, Date C, Wakai K, et al. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med. 2006;144:554-562.
35. Kim HM, Kim J. The effects of green tea on obesity and type 2 diabetes. Diab Metabol J. 2013;37:173-175.
36. Yang J, Mao Q, Xu H, et al. Tea consumption and risk of type 2 diabetes mellitus: a systematic review and meta-analysis update. BMJ Open. 2014;4:e005632.
37. Liu K, Zhou R, Wang B, et al. Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013;98:340-348.
38. Isomura T, Suzuki S, Origasa H, et al. Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. Eur J Clin Nutr. 2016;70:1340.
39. Tillisch K. Complementary and alternative medicine for gastrointestinal disorders. Clin Med (Lond). 2007;7:224-227.
40. Knowlton WM, McKemy DD. TRPM8: from cold to cancer, peppermint to pain. Curr Pharm Biotechnol. 2011;12:68-77.
41. Ford AC, Moayyedi P, Lacy BE, et al. Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl 1):S2-S26;quiz S27.
42. Ruepert L, Quartero AO, de Wit NJ, et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2011;(8):CD003460.
43. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48:505-512.
44. Cash BD, Epstein MS, Shah SM. A novel delivery system of peppermint oil is an effective therapy for irritable bowel syndrome symptoms. Digest Dis Sci. 2016;61:560-571.
45. Holtmann G, Haag S, Adam B, et al. Effects of a fixed combination of peppermint oil and caraway oil on symptoms and quality of life in patients suffering from functional dyspepsia. Phytomedicine. 2003;10(suppl 4):56-57.
46. Madisch A, Heydenreich CJ, Wieland V, et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride. A multicenter, reference-controlled double-blind equivalence study. Arzneimittelforschung. 1999;49:925-932.
47. Asao T, Kuwano H, Ide M, et al. Spasmolytic effect of peppermint oil in barium during double-contrast barium enema compared with Buscopan. Clin Radiol. 2003;58:301-305.
48. Sparks MJ, O’Sullivan P, Herrington AA, et al. Does peppermint oil relieve spasm during barium enema? Br J Radiol. 1995;68:841-843.
49. Akhavan Amjadi M, Mojab F, Kamranpour SB. The effect of peppermint oil on symptomatic treatment of pruritus in pregnant women. Iranian J Pharm Res. 2012;11:1073-1077.
50. St Cyr A, Chen A, Bradley KC, et al. Efficacy and tolerability of STOPAIN for a migraine attack. Front Neurol. 2015;6:11.
51. Borhani Haghighi A, Motazedian S, Rezaii R, et al. Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study. Int J Clin Pract. 2010;64:451-456.
52. Gobel H, Fresenius J, Heinze A, et al. Effectiveness of oleum menthae piperitae and paracetamol in therapy of headache of the tension type [German]. Nervenarzt. 1996;67:672-681.
53. Schattner P, Randerson D. Tiger Balm as a treatment of tension headache. A clinical trial in general practice. Aust Fam Physician. 1996;25:216-220.
54. Johar P, Grover V, Topp R, et al. A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness. Int J Sports Phys Ther. 2012;7:314-322.
55. Topp R, Brosky JA Jr, Pieschel D. The effect of either topical menthol or a placebo on functioning and knee pain among patients with knee OA. J Geriatr Phys Ther. 2013;36:92-99.
56. Sundstrup E, Jakobsen MD, Brandt M, et al. Acute effect of topical menthol on chronic pain in slaughterhouse workers with carpal tunnel syndrome: triple-blind, randomized placebo-controlled trial. Rehabil Res Pract. 2014;2014:310913.
57. Nair B. Final report on the safety assessment of mentha piperita (peppermint) oil, mentha piperita (peppermint) leaf extract, mentha piperita (peppermint) leaf, and mentha piperita (peppermint) leaf water. Int J Toxicol. 2001;20(Suppl 3):61-73.
58. Klingler B, Chadhary S. Peppermint oil. Am Fam Physician. 2007;75:1027-1030.
59. Nath SS, Pandey C, Roy D. A near fatal case of high dose peppermint oil ingestion—lessons learnt. Indian J Anaesth. 2012; 56:582-
PRACTICE RECOMMENDATIONS
› Consider capsaicin as an alternative to oral and topical nonsteroidal anti-inflammatory drugs to treat musculoskeletal pain in patients who don't respond to the latter. B
› Consider ordering liver function monitoring for patients using butterbur because of the risk of toxicity. C
› Recommend that patients consider drinking green tea as part of a healthy diet. B
› Recommend peppermint to patients with irritable bowel syndrome. 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
