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What is the best approach to the evaluation and treatment of chronic cough?
Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients (grade of recommendation: C, based on case series at referral centers).
Evidence summary
By definition, chronic cough persists past 3 to 8 weeks.1 Irwin proposed an algorithm to evaluate chronic cough in 19812 that has successfully diagnosed and treated chronic cough 82% to 100% of the time in referral centers.2-6 Among patients in this setting who are not using tobacco or ACE inhibitors (assuming a normal or stable chest x-ray), most have PNDS, asthma, GERD, or a combination of these diagnoses.2-5 The protocol evaluates for these 3 conditions. The key weakness of the protocol is that a positive diagnostic test result does not mean that treatment for that condition will relieve the cough.5 Recently, empiric treatment before diagnostic testing has been recommended for primary care.1
An important unanswered clinical question is whether empiric treatment trials or diagnostic testing–directed trials are the best approach.7 Initial empiric treatment for PNDS appears reasonable, since it is the most common single cause of chronic cough,2,4-6 and symptoms and signs and diagnostic tests for PNDS are unreliable.3,6 One prospective study using empiric PNDS treatment as a first step decreased the number of tests required and the mean time to diagnosis compared with previously published studies.6 No studies were found evaluating empiric treatment for asthma before diagnosis. Multiple studies report a 100% negative predictive value for the methacholine challenge test,3-5 but this carries some risk and is not universally available. Empiric treatment of GERD with omeprazole before diagnostic testing with a 24-hour pH probe was evaluated in 1 study. Cough resolved with treatment in only 6 of 17 patients with a positive 24-hour pH probe.8 In another study, 5 of 5 patients with cough due to GERD responded to an H2-blocker.6 The negative predictive value of a 24-hour pH probe is between 90% and 100%,3-6 but this may also be reserved for those who fail initial empiric therapy.
The best timing of the chest x-ray is also unclear. The diagnostic protocol has been historically evaluated in patients with a normal or stable chest x-ray.2-5 One study used a protocol that delayed the chest x-ray for 2 weeks, until after empiric treatment for PNDS and evaluation for asthma. These authors eliminated half of the x-rays and achieved results equivalent to previous studies.6
A recommended approach based on available literature is outlined in the Table 1. Keep in mind that all studies have been done in referral centers.
Recommendations from others
The American College of Chest Physicians recommends the following order of interventions: stop ACE inhibitors, obtain chest x-ray, avoid irritants (such as tobacco), evaluate for PNDS, evaluate for asthma, evaluate for GERD, consider special studies, and reconsider adequacy oftreatments.9
Sang-Ick Chang, MD
San Francisco, California
Chronic cough is an extremely common and vexing problem in primary care. The approach recommended above is helpful and sensible, and I offer a few comments. Given the 3- to 8-week minimum definition of chronic cough, many patients who present with “chronic” cough to their primary care provider will have a postviral cough that will go away on its own. This includes patients taking ACE inhibitors, and how long they are allowed to cough before you stop the ACE inhibitor is a difficult question. Also, before blaming a new “chronic” cough on tobacco use, remember that smokers get reflux, postnasal drip, and asthma at least as often as nonsmokers, not to mention lung cancer. Finally, methacholine challenge testing and pH probe testing are not readily available in my public institution, but even where they are available, I think empiric treatment is more cost-effective and more acceptable to patients.
1. Lawler R. An office approach to the diagnosis of chronic cough. Am Fam Physician 1998;58:2015-22.
2. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcomes of specific therapy. Am Review Respir Dis 1981;123:413-17.
3. McGarvey LP, Heaney LG, Lawson JT, et al. Evaluation and outcomes of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax 1998;53:738-43.
4. Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med 1998;158:1222-28.
5. Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes and key components of the diagnostic evaluation and outcomes of specific therapy. Am Rev Respir Dis 1990;141:640-47.
6. Pratter MR, Bartter T, Akers S, Dubois J. An algorithmic approach to chronic cough. Ann Intern Med 1993;119:977-83.
7. Irwin RS, Madison JM. Symptom research on chronic cough: a historical perspective. Ann Intern Med 2001;134:809-14.
8. Ours TM, Kavauru MS, Schultz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 1999;94:3131-38.
9. American College of Chest Physicians. Managing cough as a defense mechanism and as a symptom. Figures accessed at:www.chestnet.org/health.science.policy/quick.reference.guides/coughqrg.figures.html.
Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients (grade of recommendation: C, based on case series at referral centers).
Evidence summary
By definition, chronic cough persists past 3 to 8 weeks.1 Irwin proposed an algorithm to evaluate chronic cough in 19812 that has successfully diagnosed and treated chronic cough 82% to 100% of the time in referral centers.2-6 Among patients in this setting who are not using tobacco or ACE inhibitors (assuming a normal or stable chest x-ray), most have PNDS, asthma, GERD, or a combination of these diagnoses.2-5 The protocol evaluates for these 3 conditions. The key weakness of the protocol is that a positive diagnostic test result does not mean that treatment for that condition will relieve the cough.5 Recently, empiric treatment before diagnostic testing has been recommended for primary care.1
An important unanswered clinical question is whether empiric treatment trials or diagnostic testing–directed trials are the best approach.7 Initial empiric treatment for PNDS appears reasonable, since it is the most common single cause of chronic cough,2,4-6 and symptoms and signs and diagnostic tests for PNDS are unreliable.3,6 One prospective study using empiric PNDS treatment as a first step decreased the number of tests required and the mean time to diagnosis compared with previously published studies.6 No studies were found evaluating empiric treatment for asthma before diagnosis. Multiple studies report a 100% negative predictive value for the methacholine challenge test,3-5 but this carries some risk and is not universally available. Empiric treatment of GERD with omeprazole before diagnostic testing with a 24-hour pH probe was evaluated in 1 study. Cough resolved with treatment in only 6 of 17 patients with a positive 24-hour pH probe.8 In another study, 5 of 5 patients with cough due to GERD responded to an H2-blocker.6 The negative predictive value of a 24-hour pH probe is between 90% and 100%,3-6 but this may also be reserved for those who fail initial empiric therapy.
The best timing of the chest x-ray is also unclear. The diagnostic protocol has been historically evaluated in patients with a normal or stable chest x-ray.2-5 One study used a protocol that delayed the chest x-ray for 2 weeks, until after empiric treatment for PNDS and evaluation for asthma. These authors eliminated half of the x-rays and achieved results equivalent to previous studies.6
A recommended approach based on available literature is outlined in the Table 1. Keep in mind that all studies have been done in referral centers.
Recommendations from others
The American College of Chest Physicians recommends the following order of interventions: stop ACE inhibitors, obtain chest x-ray, avoid irritants (such as tobacco), evaluate for PNDS, evaluate for asthma, evaluate for GERD, consider special studies, and reconsider adequacy oftreatments.9
Sang-Ick Chang, MD
San Francisco, California
Chronic cough is an extremely common and vexing problem in primary care. The approach recommended above is helpful and sensible, and I offer a few comments. Given the 3- to 8-week minimum definition of chronic cough, many patients who present with “chronic” cough to their primary care provider will have a postviral cough that will go away on its own. This includes patients taking ACE inhibitors, and how long they are allowed to cough before you stop the ACE inhibitor is a difficult question. Also, before blaming a new “chronic” cough on tobacco use, remember that smokers get reflux, postnasal drip, and asthma at least as often as nonsmokers, not to mention lung cancer. Finally, methacholine challenge testing and pH probe testing are not readily available in my public institution, but even where they are available, I think empiric treatment is more cost-effective and more acceptable to patients.
Potentially cough-inducing agents, such as tobacco products and angiotensin-converting enzyme (ACE) inhibitors, should be eliminated first. Evaluation and treatment for postnasal drip syndrome (PNDS), asthma, and gastroesophageal reflux disease (GERD) should remedy symptoms in the vast majority of patients (grade of recommendation: C, based on case series at referral centers).
Evidence summary
By definition, chronic cough persists past 3 to 8 weeks.1 Irwin proposed an algorithm to evaluate chronic cough in 19812 that has successfully diagnosed and treated chronic cough 82% to 100% of the time in referral centers.2-6 Among patients in this setting who are not using tobacco or ACE inhibitors (assuming a normal or stable chest x-ray), most have PNDS, asthma, GERD, or a combination of these diagnoses.2-5 The protocol evaluates for these 3 conditions. The key weakness of the protocol is that a positive diagnostic test result does not mean that treatment for that condition will relieve the cough.5 Recently, empiric treatment before diagnostic testing has been recommended for primary care.1
An important unanswered clinical question is whether empiric treatment trials or diagnostic testing–directed trials are the best approach.7 Initial empiric treatment for PNDS appears reasonable, since it is the most common single cause of chronic cough,2,4-6 and symptoms and signs and diagnostic tests for PNDS are unreliable.3,6 One prospective study using empiric PNDS treatment as a first step decreased the number of tests required and the mean time to diagnosis compared with previously published studies.6 No studies were found evaluating empiric treatment for asthma before diagnosis. Multiple studies report a 100% negative predictive value for the methacholine challenge test,3-5 but this carries some risk and is not universally available. Empiric treatment of GERD with omeprazole before diagnostic testing with a 24-hour pH probe was evaluated in 1 study. Cough resolved with treatment in only 6 of 17 patients with a positive 24-hour pH probe.8 In another study, 5 of 5 patients with cough due to GERD responded to an H2-blocker.6 The negative predictive value of a 24-hour pH probe is between 90% and 100%,3-6 but this may also be reserved for those who fail initial empiric therapy.
The best timing of the chest x-ray is also unclear. The diagnostic protocol has been historically evaluated in patients with a normal or stable chest x-ray.2-5 One study used a protocol that delayed the chest x-ray for 2 weeks, until after empiric treatment for PNDS and evaluation for asthma. These authors eliminated half of the x-rays and achieved results equivalent to previous studies.6
A recommended approach based on available literature is outlined in the Table 1. Keep in mind that all studies have been done in referral centers.
Recommendations from others
The American College of Chest Physicians recommends the following order of interventions: stop ACE inhibitors, obtain chest x-ray, avoid irritants (such as tobacco), evaluate for PNDS, evaluate for asthma, evaluate for GERD, consider special studies, and reconsider adequacy oftreatments.9
Sang-Ick Chang, MD
San Francisco, California
Chronic cough is an extremely common and vexing problem in primary care. The approach recommended above is helpful and sensible, and I offer a few comments. Given the 3- to 8-week minimum definition of chronic cough, many patients who present with “chronic” cough to their primary care provider will have a postviral cough that will go away on its own. This includes patients taking ACE inhibitors, and how long they are allowed to cough before you stop the ACE inhibitor is a difficult question. Also, before blaming a new “chronic” cough on tobacco use, remember that smokers get reflux, postnasal drip, and asthma at least as often as nonsmokers, not to mention lung cancer. Finally, methacholine challenge testing and pH probe testing are not readily available in my public institution, but even where they are available, I think empiric treatment is more cost-effective and more acceptable to patients.
1. Lawler R. An office approach to the diagnosis of chronic cough. Am Fam Physician 1998;58:2015-22.
2. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcomes of specific therapy. Am Review Respir Dis 1981;123:413-17.
3. McGarvey LP, Heaney LG, Lawson JT, et al. Evaluation and outcomes of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax 1998;53:738-43.
4. Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med 1998;158:1222-28.
5. Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes and key components of the diagnostic evaluation and outcomes of specific therapy. Am Rev Respir Dis 1990;141:640-47.
6. Pratter MR, Bartter T, Akers S, Dubois J. An algorithmic approach to chronic cough. Ann Intern Med 1993;119:977-83.
7. Irwin RS, Madison JM. Symptom research on chronic cough: a historical perspective. Ann Intern Med 2001;134:809-14.
8. Ours TM, Kavauru MS, Schultz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 1999;94:3131-38.
9. American College of Chest Physicians. Managing cough as a defense mechanism and as a symptom. Figures accessed at:www.chestnet.org/health.science.policy/quick.reference.guides/coughqrg.figures.html.
1. Lawler R. An office approach to the diagnosis of chronic cough. Am Fam Physician 1998;58:2015-22.
2. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcomes of specific therapy. Am Review Respir Dis 1981;123:413-17.
3. McGarvey LP, Heaney LG, Lawson JT, et al. Evaluation and outcomes of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax 1998;53:738-43.
4. Smyrnios NA, Irwin RS, Curley FJ, French CL. From a prospective study of chronic cough: diagnostic and therapeutic aspects in older adults. Arch Intern Med 1998;158:1222-28.
5. Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes and key components of the diagnostic evaluation and outcomes of specific therapy. Am Rev Respir Dis 1990;141:640-47.
6. Pratter MR, Bartter T, Akers S, Dubois J. An algorithmic approach to chronic cough. Ann Intern Med 1993;119:977-83.
7. Irwin RS, Madison JM. Symptom research on chronic cough: a historical perspective. Ann Intern Med 2001;134:809-14.
8. Ours TM, Kavauru MS, Schultz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 1999;94:3131-38.
9. American College of Chest Physicians. Managing cough as a defense mechanism and as a symptom. Figures accessed at:www.chestnet.org/health.science.policy/quick.reference.guides/coughqrg.figures.html.
Evidence-based answers from the Family Physicians Inquiries Network
Should we still be using theophylline to treat asthma?
Inflammatory myopathies: Narrowing the differential diagnosis
Do patients with local reactions to allergy shots require dosage reductions for subsequent injections?
BACKGROUND: Many physicians reduce the dose of allergen immunotherapy when patients have significant local reactions to their allergy shots, believing that these patients are at higher risk for systemic reactions. This dose reduction is made despite the fact that the World Health Organization stated in a position paper on allergen immunotherapy that local reactions are not predictive of subsequent systemic reactions.
POPULATION STUDIED: This study was conducted at a single-site Air Force allergy clinic. During the 18-month study period 12,926 allergy shots were given. No further demographic details were provided.
STUDY DESIGN AND VALIDITY: This nonconcurrent cohort study compared reaction rates to allergy shots for 9 months (October 1996 to June 1997) before an intervention with reaction rates for the 9 months (October 1997 to June 1998) after the intervention. The first group (8076 injections) had their allergy shot dose reduced if they had an immediate local reaction 20 mm or larger or if they had any localized swelling that persisted more than 12 hours. The second group (4850 injections) had no dose reduction for immediate and local reactions unless the reaction was larger than the patient’s hand (adult=8-10 cm) or caused the patient significant discomfort. In most respects the study groups can be considered similar. In fact, in many instances the same subject was probably included in both groups (because most patients receive allergy shots for several years they would have been captured in both 9-month study periods). The potential for differences in the study groups comes from selection bias and those lost to follow-up. The first 9-month period included 8076 injections, while the second 9-month period had only 4850 injections. The authors state that this is because there was difficulty getting extract during the second 9-month period, which delayed the initiation of immunotherapy for some. Because allergy shots can be grouped into 2 phases (build-up and maintenance) and the traditional teaching is that reactions are less common in patients getting maintenance shots, the second group may have had a higher proportion receiving the less-risky maintenance injections. The follow-up of both groups was by review of clinic records, of which 74% were located for the first group and 78% for the second group. Bias could be introduced if the patients who were lost to follow-up were significantly different.
OUTCOMES MEASURED: Systemic reaction rates during the 2 periods were determined. Among those with a systemic reaction, the number of times a local reaction immediately preceded the systemic reaction and the total number of previous local reactions were also determined.
RESULTS: Systemic reaction rates were not statistically different during the 2 9-month periods (0.8% before vs 1.0% after, P=.24). The number of times a local reaction preceded a systemic reaction in the first period was not significantly different from the second 9-month period (18.8% before vs 10.5% after, P=.37). The total local reaction rate for those with systemic reactions was not significantly different during the 2 study periods (7.3% before vs 4.7% after, P=.07). The calculated sensitivity for a local reaction predicting a systemic reaction at the next dose was 15% with a positive predictive value of a local reaction for a subsequent systemic reaction of 17%.
This study supports recommendations that an allergy shot dosage reduction is not needed after a local reaction to the previous dose, unless the reaction is larger than 8 cm. There were no significant differences in the rate of systemic reactions between those who had their dose reduced because of a local reaction and those who did not. Also, a local reaction after an allergy shot is a poor predictor of subsequent systemic reactions. Such a no-adjustment policy should get patients to their maintenance dose more quickly and may reduce dosing errors in patients receiving 2 or more vaccines. For patients using more than one vaccine, typical dose-adjustment policies prompt reduction of just one of the vaccines. After this the patient would be on dissimilar doses and have a higher potential for dosing error.
BACKGROUND: Many physicians reduce the dose of allergen immunotherapy when patients have significant local reactions to their allergy shots, believing that these patients are at higher risk for systemic reactions. This dose reduction is made despite the fact that the World Health Organization stated in a position paper on allergen immunotherapy that local reactions are not predictive of subsequent systemic reactions.
POPULATION STUDIED: This study was conducted at a single-site Air Force allergy clinic. During the 18-month study period 12,926 allergy shots were given. No further demographic details were provided.
STUDY DESIGN AND VALIDITY: This nonconcurrent cohort study compared reaction rates to allergy shots for 9 months (October 1996 to June 1997) before an intervention with reaction rates for the 9 months (October 1997 to June 1998) after the intervention. The first group (8076 injections) had their allergy shot dose reduced if they had an immediate local reaction 20 mm or larger or if they had any localized swelling that persisted more than 12 hours. The second group (4850 injections) had no dose reduction for immediate and local reactions unless the reaction was larger than the patient’s hand (adult=8-10 cm) or caused the patient significant discomfort. In most respects the study groups can be considered similar. In fact, in many instances the same subject was probably included in both groups (because most patients receive allergy shots for several years they would have been captured in both 9-month study periods). The potential for differences in the study groups comes from selection bias and those lost to follow-up. The first 9-month period included 8076 injections, while the second 9-month period had only 4850 injections. The authors state that this is because there was difficulty getting extract during the second 9-month period, which delayed the initiation of immunotherapy for some. Because allergy shots can be grouped into 2 phases (build-up and maintenance) and the traditional teaching is that reactions are less common in patients getting maintenance shots, the second group may have had a higher proportion receiving the less-risky maintenance injections. The follow-up of both groups was by review of clinic records, of which 74% were located for the first group and 78% for the second group. Bias could be introduced if the patients who were lost to follow-up were significantly different.
OUTCOMES MEASURED: Systemic reaction rates during the 2 periods were determined. Among those with a systemic reaction, the number of times a local reaction immediately preceded the systemic reaction and the total number of previous local reactions were also determined.
RESULTS: Systemic reaction rates were not statistically different during the 2 9-month periods (0.8% before vs 1.0% after, P=.24). The number of times a local reaction preceded a systemic reaction in the first period was not significantly different from the second 9-month period (18.8% before vs 10.5% after, P=.37). The total local reaction rate for those with systemic reactions was not significantly different during the 2 study periods (7.3% before vs 4.7% after, P=.07). The calculated sensitivity for a local reaction predicting a systemic reaction at the next dose was 15% with a positive predictive value of a local reaction for a subsequent systemic reaction of 17%.
This study supports recommendations that an allergy shot dosage reduction is not needed after a local reaction to the previous dose, unless the reaction is larger than 8 cm. There were no significant differences in the rate of systemic reactions between those who had their dose reduced because of a local reaction and those who did not. Also, a local reaction after an allergy shot is a poor predictor of subsequent systemic reactions. Such a no-adjustment policy should get patients to their maintenance dose more quickly and may reduce dosing errors in patients receiving 2 or more vaccines. For patients using more than one vaccine, typical dose-adjustment policies prompt reduction of just one of the vaccines. After this the patient would be on dissimilar doses and have a higher potential for dosing error.
BACKGROUND: Many physicians reduce the dose of allergen immunotherapy when patients have significant local reactions to their allergy shots, believing that these patients are at higher risk for systemic reactions. This dose reduction is made despite the fact that the World Health Organization stated in a position paper on allergen immunotherapy that local reactions are not predictive of subsequent systemic reactions.
POPULATION STUDIED: This study was conducted at a single-site Air Force allergy clinic. During the 18-month study period 12,926 allergy shots were given. No further demographic details were provided.
STUDY DESIGN AND VALIDITY: This nonconcurrent cohort study compared reaction rates to allergy shots for 9 months (October 1996 to June 1997) before an intervention with reaction rates for the 9 months (October 1997 to June 1998) after the intervention. The first group (8076 injections) had their allergy shot dose reduced if they had an immediate local reaction 20 mm or larger or if they had any localized swelling that persisted more than 12 hours. The second group (4850 injections) had no dose reduction for immediate and local reactions unless the reaction was larger than the patient’s hand (adult=8-10 cm) or caused the patient significant discomfort. In most respects the study groups can be considered similar. In fact, in many instances the same subject was probably included in both groups (because most patients receive allergy shots for several years they would have been captured in both 9-month study periods). The potential for differences in the study groups comes from selection bias and those lost to follow-up. The first 9-month period included 8076 injections, while the second 9-month period had only 4850 injections. The authors state that this is because there was difficulty getting extract during the second 9-month period, which delayed the initiation of immunotherapy for some. Because allergy shots can be grouped into 2 phases (build-up and maintenance) and the traditional teaching is that reactions are less common in patients getting maintenance shots, the second group may have had a higher proportion receiving the less-risky maintenance injections. The follow-up of both groups was by review of clinic records, of which 74% were located for the first group and 78% for the second group. Bias could be introduced if the patients who were lost to follow-up were significantly different.
OUTCOMES MEASURED: Systemic reaction rates during the 2 periods were determined. Among those with a systemic reaction, the number of times a local reaction immediately preceded the systemic reaction and the total number of previous local reactions were also determined.
RESULTS: Systemic reaction rates were not statistically different during the 2 9-month periods (0.8% before vs 1.0% after, P=.24). The number of times a local reaction preceded a systemic reaction in the first period was not significantly different from the second 9-month period (18.8% before vs 10.5% after, P=.37). The total local reaction rate for those with systemic reactions was not significantly different during the 2 study periods (7.3% before vs 4.7% after, P=.07). The calculated sensitivity for a local reaction predicting a systemic reaction at the next dose was 15% with a positive predictive value of a local reaction for a subsequent systemic reaction of 17%.
This study supports recommendations that an allergy shot dosage reduction is not needed after a local reaction to the previous dose, unless the reaction is larger than 8 cm. There were no significant differences in the rate of systemic reactions between those who had their dose reduced because of a local reaction and those who did not. Also, a local reaction after an allergy shot is a poor predictor of subsequent systemic reactions. Such a no-adjustment policy should get patients to their maintenance dose more quickly and may reduce dosing errors in patients receiving 2 or more vaccines. For patients using more than one vaccine, typical dose-adjustment policies prompt reduction of just one of the vaccines. After this the patient would be on dissimilar doses and have a higher potential for dosing error.