EVIDENCE SUMMARY

A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.¹ At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).

At 3 and 6 months, HA improves pain, but not function, more than CS

Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.² All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.

Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.

Triamcinolone improves pain, function, but not for long

A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.³ Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.

The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.

Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.

 

 

HA (mostly) improves pain, function more than betamethasone

A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.⁴ Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.

Inconsistent evidence shows a small amount of pain relief at one week to 3 months with corticosteroid injections.

The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).

The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).⁴

RECOMMENDATIONS

The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.⁵ They also couldn’t recommend using HA (SOR: strong).

The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.⁶ In 2014, NICE recommended against offering intra-articular HA injections for managing OA.

The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).⁷ They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).

EVIDENCE SUMMARY

A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.¹ At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).

At 3 and 6 months, HA improves pain, but not function, more than CS

Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.² All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.

Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.

Triamcinolone improves pain, function, but not for long

A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.³ Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.

The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.

Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.

 

 

HA (mostly) improves pain, function more than betamethasone

A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.⁴ Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.

Inconsistent evidence shows a small amount of pain relief at one week to 3 months with corticosteroid injections.

The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).

The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).⁴

RECOMMENDATIONS

The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.⁵ They also couldn’t recommend using HA (SOR: strong).

The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.⁶ In 2014, NICE recommended against offering intra-articular HA injections for managing OA.

The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).⁷ They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).

EVIDENCE SUMMARY

A 2015 network meta-analysis of 137 RCTs with 33,243 patients (ages 45-76 years) with knee OA compared the effectiveness of a variety of treatments including intra-articular CS and HA.¹ At 3 months, the effect on pain was not significantly different between the CS and HA groups (12 trials; effect size [ES]=0.02; 95% confidence interval [CI], -0.12 to 0.17). However, a small but significant improvement in function was noted (scoring system not defined) at 3 months favoring HA (ES=0.24; 95% CI, 0.06-0.43; number of trials not specified).

At 3 and 6 months, HA improves pain, but not function, more than CS

Another meta-analysis published in 2015 examined the effectiveness of intra-articular CS and HA in 7 RCTs with 583 patients with knee OA.² All 7 trials were included in the network meta-analysis and discussed separately to evaluate different time points.

Pain at one month wasn’t significantly different using a visual analog score (VAS) of one to 100 (4 trials; 245 patients; mean difference [MD]=1.66 points; 95% CI, -0.90 to 4.23). At 3 and 6 months, the HA group reported significantly reduced pain compared with the CS group (3 months: 3 trials; 320 patients; MD=12.58 points; 95% CI, -17.76 to -7.40; 6 months: 5 trials; 411 patients; MD=9.01 points; 95% CI, -12.62 to -5.40). There were no significant differences in function outcomes (Index of severity for OA of the knee by Lequesne et al; The Knee Society Clinical Rating System), maximum flexion, or adverse events.

Triamcinolone improves pain, function, but not for long

A 2016 double-blind RCT of 110 patients with knee OA compared intra-articular HA and triamcinolone, assessing pain and function at intervals between 24 hours and 6 months.³ Patients in the HA group received a single injection of 6 mL hylan G-F 20 (Synvisc); patients in the CS group received 1 mL of triamcinolone acetonide 40 mg and 5 mL of 1% lidocaine with epinephrine.

The CS group reported significantly less pain (VAS score 1 to 100) at 24 hours than the HA group (24 points vs 36 points; P=.002); relief lasted as long as one week (14 points vs 23 points; P=.018). After the first week, no difference was seen in pain between groups for as long as 6 months.

Function, assessed by a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC 1 to 100; higher score indicates worse pain, stiffness, and function) showed a significant improvement with CS at 2 weeks (25 points vs 31 points; P=.03), but no difference at any other time point up to 6 months.

 

 

HA (mostly) improves pain, function more than betamethasone

A 2015 RCT of 200 patients with knee OA compared the effectiveness of intra-articular HA and betamethasone.⁴ Evaluators were blinded and assessments were made at 3, 6, 9, and 12 months. The HA group received 2.5 mL of 1% HA (Suprahyal); the CS group received betamethasone dipropionate 5 mg plus betamethasone sodium phosphate 2 mg in 1 mL.

Inconsistent evidence shows a small amount of pain relief at one week to 3 months with corticosteroid injections.

The CS group had significantly less pain (VAS 1 to 10) at 3 months compared with the HA group (2.2 points vs 3.1 points; P=.004), but the HA group had less pain at all other time points (6 months: 3.9 points vs 2.4 points; P=.0001; 9 months: 5.5 points vs 3.6 points; P=.0001; 12 months: 6 points vs 4.1 points; P=.0001).

The WOMAC function subscores (0 to 68; lower indicates more function) were significantly better at all follow-up points in the HA group compared with the CS group (3 months: 19 vs 25; P=.0001; 6 months: 17 vs 29; P=.0001; 9 months: 25 vs 42; P=.0001; 12 months: 28 vs 42; P=.0001).⁴

RECOMMENDATIONS

The American Academy of Orthopaedic Surgeons 2013 work group couldn’t recommend for or against using intra-articular CS for patients with symptomatic knee OA based on inconclusive evidence.⁵ They also couldn’t recommend using HA (SOR: strong).

The National Institute for Health and Care Excellence (NICE) stated in 2008 that intra-articular CS injections should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with OA.⁶ In 2014, NICE recommended against offering intra-articular HA injections for managing OA.

The US Veterans Administration and Department of Defense have issued guidelines stating that clinicians may consider intra-articular CS injections for patients with symptomatic knee OA (US Preventive Services Task Force [USPSTF] Grade B).⁷ They report insufficient evidence to recommend for or against the use of intra-articular HA with the caveat that HA may be considered for patients who don’t respond adequately to nonpharmacologic measures and who have an inadequate response, intolerable adverse events, or contraindications to other pharmacologic therapies (USPSTF Grade I).

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

At least I can feel better about the 4 cups of coffee I drink every day!

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 the Natural Medicine Database (https://naturalmedicines.therapeuticresearch.com).

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

At least I can feel better about the 4 cups of coffee I drink every day!

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 the Natural Medicine Database (https://naturalmedicines.therapeuticresearch.com).

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

At least I can feel better about the 4 cups of coffee I drink every day!

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 the Natural Medicine Database (https://naturalmedicines.therapeuticresearch.com).

Now I will finish my fourth cup of coffee . . .

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.

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.

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

We should not only focus on this modifiable risk factor (hypertension) to reduce CVD risk and mortality, but we should do so to the evidence-based goal.

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.

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.

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

We should not only focus on this modifiable risk factor (hypertension) to reduce CVD risk and mortality, but we should do so to the evidence-based goal.

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.

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.

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

We should not only focus on this modifiable risk factor (hypertension) to reduce CVD risk and mortality, but we should do so to the evidence-based goal.

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.

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

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

While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines.

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:

1. 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
2. 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
3. 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
4. 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.
5. 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, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions.

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

While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines.

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:

1. 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
2. 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
3. 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
4. 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.
5. 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, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions.

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

While it is tempting to make generalizations about BP treatment targets, we owe it to our patients to understand the nuances of applicable guidelines.

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:

1. 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
2. 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
3. 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
4. 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.
5. 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, we strongly emphasized that comorbidities, frailty, and dementia greatly impact treatment decisions.

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.

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

Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder.

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 series of 5 patients who chose nonoperative treatment, Geaney and Mazzocca reported that patients experienced a 15% loss of supination strength at 4.5 years follow-up compared with the uninjured side.¹

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

Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder.

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 series of 5 patients who chose nonoperative treatment, Geaney and Mazzocca reported that patients experienced a 15% loss of supination strength at 4.5 years follow-up compared with the uninjured side.¹

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

Nonoperative management includes gentle range-of-motion exercises for the prevention of contractures of the elbow and shoulder.

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 series of 5 patients who chose nonoperative treatment, Geaney and Mazzocca reported that patients experienced a 15% loss of supination strength at 4.5 years follow-up compared with the uninjured side.¹

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.

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.

Odontogenic sinus tract begins with dental caries, which progress to degeneration of the dental pulp and formation of periapical abscesses.

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.

Odontogenic sinus tract begins with dental caries, which progress to degeneration of the dental pulp and formation of periapical abscesses.

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.

Odontogenic sinus tract begins with dental caries, which progress to degeneration of the dental pulp and formation of periapical abscesses.

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 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.

A chest x-ray has low sensitivity and specificity for interstitial lung disease and can frequently be misinterpreted, as occurred with our 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.

Patients with interstitial lung disease have a life expectancy that averages 2 to 4 years from diagnosis.

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.

A chest x-ray has low sensitivity and specificity for interstitial lung disease and can frequently be misinterpreted, as occurred with our 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.

Patients with interstitial lung disease have a life expectancy that averages 2 to 4 years from diagnosis.

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.

A chest x-ray has low sensitivity and specificity for interstitial lung disease and can frequently be misinterpreted, as occurred with our 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.

Patients with interstitial lung disease have a life expectancy that averages 2 to 4 years from diagnosis.

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].

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.

This review went one step further by examining passage rates by stone size and revealed that passage of larger stones (5-10 mm) increased with 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.

This review went one step further by examining passage rates by stone size and revealed that passage of larger stones (5-10 mm) increased with 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.

This review went one step further by examining passage rates by stone size and revealed that passage of larger stones (5-10 mm) increased with 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.

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

1. 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.
2. Defer the second dose of HAV vaccine if it is in short supply.
3. Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
4. 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 (TABLE^2,14). 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

1. 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.
2. Defer the second dose of HAV vaccine if it is in short supply.
3. Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
4. 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 (TABLE^2,14). 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

1. 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.
2. Defer the second dose of HAV vaccine if it is in short supply.
3. Perform pre-vaccination serologic testing to identify those who are immune, thereby preserving vaccine and reducing costs.
4. 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 (TABLE^2,14). 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.